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"senescence" Definitions
  1. the process of becoming old and showing the effects of being old

676 Sentences With "senescence"

How to use senescence in a sentence? Find typical usage patterns (collocations)/phrases/context for "senescence" and check conjugation/comparative form for "senescence". Mastering all the usages of "senescence" from sentence examples published by news publications.

One particularly critical contributor of aging, however, is a process known as cellular senescence (senescence being a fancy word for aging).
The most immediate challenge will be access to anti-senescence treatment.
Stars are still being born, but the universe seems to be approaching senescence.
That sounds unlikely, given that we are in the senescence of a bull cycle.
In industrialized countries, old age would no longer mean a ghostly, semidemented, decades-long senescence.
Aging is known as senescence and senescence is disease..my father blew his head off when i was a child and my mother is a grown child thats dying from diabetees and living on candy and potato chips..iv been sneaking astragalus membranceus into her food to keep her alive..GERON corporation did research proving that astragalus from chinese medicine reverses cellular senescence..iv been talking to the white house and darpa trying to find a job or something?
He and his colleagues also found genes that influence cell senescence or the deterioration of individual cells.
"Quite a bit is already known about resistance to radiation, osteoporosis, cancer, and senescence in mice," he says.
SMART is an acronym for "senescence modulated abscission regulated technologies," essentially a specialized gene pool of the tree.
The new increase would be brought about by specific anti-senescence drugs, some of which may already exist.
De Grey himself has outlined a plan, called Strategies for Engineered Negligible Senescence, to stall—and even reverse—the aging process.
The study also bolsters the theory that cellular senescence is a mechanism that contributes to cancer and the proliferation of tumors.
His nonprofit, Strategies for Engineered Negligible Senescence, focuses on research in heart disease and Alzheimer's, and other common illnesses and diseases.
For baseball players, who skip straight from an immature adolescence into a premature senescence, that realization often comes early, and brutally.
For that, it's worth tasting wines at all levels of aging, from young through adolescence and middle age to doughty senescence.
"Dara Torres, swimmer, U.S.A."I'd proven to the world that maturity, experience, dedication, and ingenuity can make up for a little senescence.
The answer is that senescence happens in a "selection shadow" -- that is, after organisms have already reproduced and passed on their genes.
Until we're all brain patterns on computers, there are still forces that do not bend to our wants, including senescence and death.
There are ways in which we have passed from eros to thanatos — from the chaos of unrestrained desire to the stability of senescence.
They produce pro-inflammatory factors called cytokines which move neighbouring cells to senescence; chronic progressive inflammation of this sort drives various age-related diseases.
Senescence, the general dwindling of prowess experienced by all as time takes its toll, is coming under scrutiny from doctors and biologists (see article).
Lydia died glamorously of a drug overdose at 27, leaving the remaining three band members to round the corner on hipster senescence without her.
An expert in cephalopods at Swansea University, Ed Pope, attributed the octopus climb-out to senescence — the rapid aging and quick onset of death.
He predicts that humans will eventually reach a stage of "negligible senescence," that is, a state in which aging is so slow that it's imperceptible.
Many of their existing T cells showed signs of senescence, which means that they had grown feeble and were unlikely to fight infections well anymore.
It's a little shocking to see him looking not just gray but frail, as if his almost-60 body harbored a soul in deep senescence.
Maggie is a woman on the edge of something other than her metaphorical tin roof; if not senescence, then the farthest side of youthful splendor.
The fourth book, Tehanu, was published some 18 years later, in 1990, and features two of the cycle's main characters, Ged and Tenar, in their senescence.
Growing old -- the 'why' as well as the 'how' Ageing -- or "senescence", to use the biological term -- is defined as a decline in physiological condition with age.
The scientific term for the color change is leaf senescence, when deciduous trees pack up their summer clothes and prepare to sleep naked through the long frigid winter.
That's because the genes in the cambium contain no program for senescence, or death, they say, but continue their program for making defenses even after hundreds of years.
It is, transhumanists say, "deathist" to argue that halting senescence through technological interventions is wrong: dying from old age should be no more involuntary than dying from childhood leukemia.
With each replication, a little more is sliced off the ends of the telomeres, and when they get too short, a cell stops replicating—a state called cell senescence.
Beverley Magennis, Los Ranchos, N.M. In his cover story, Hylton describes Close as Lear-­like, a hermit teetering on the brink of senescence, his expression childlike, his appearance clownish.
The researchers compared cells extracted from between the tree wood and bark and found that there was no change in the expression of genes related to biological aging, called senescence.
Once they have reached the limits of their reproductive powers, they enter a state called "senescence", in which they carry on performing their duties but stop making new copies of themselves.
It explains not only general senescence, but also why dementia, cancer, cardiovascular problems, arthritis and many other things are guarded against in youth, but crammed into old age once reproduction is done with.
Other potential clinical trial scenarios include testing whether the drugs could alleviate frailty in older adults or could treat conditions associated with chemotherapy or radiotherapy, since radiation can produce cellular senescence, Kirkland said.
He shares why he believes in open source research, how cellular senescence is a particular area of interest right now, what his personal health routine is and how he thinks about the singularity.
But Howard Neufeld, a professor of biology at Appalachian State University in North Carolina, said climate change could eventually affect the complex processes in leaf senescence and lower anthocyanin production, dulling the autumn reds.
"Protection from bright light (and probably UV light as well) during the process of leaf senescence is the best explanation for why the leaves of some trees turn red in autumn" Dr. Guy wrote in an email.
We amass damage as we live, and damage to our DNA leads to cell disease and senescence; the telomeres that cap our chromosomes shorten and fray, placing a hard stop on the number of times our cells divide.
They also suggest testing whether the drugs could treat diseases for which there are no medicines proven to slow the progression of that disease, such as idiopathic pulmonary fibrosis, a cell senescence-associated disease that affects the lungs.
Tom Margittai, who with a partner rejuvenated the Four Seasons restaurant from autumnal senescence into a majestic — and, for the first time, profitable — three-star magnet for Manhattan's power brokers, died on Friday in Santa Fe, N.M. He was 90.
In recent years, the science moving through the research pipeline—much of it in mice—has shown potential in reversing cell senescence and aging-related damage, which, if effective in humans could, in theory, offer endless opportunities to turn back the clock.
For men, it added a layer of nobility, even virility; for women it meant senescence, the end of fertility and thus usefulness — there could be beauty, but with a note of poignancy: Oh, she must have been lovely when she was young!
In an office not far from Google's headquarters in Mountain View, with a beard to his belt buckle and a ponytail to match, British biomedical gerontologist Aubrey De Grey is enjoying the growing clamor about conquering aging, or "senescence," as he calls it.
Short-lived species seem to be able to "trade in" their investment in growth and sexual reproduction in return for slowing down the ageing process -- switching to a physiological state in which they instead invest in maintenance of body condition and warding off senescence.
I even feared your meteoric ascent might rival my own: A Harvard alum by age 15, biotech innovator, holder of twenty exclusive genetic patents before 25, and the first to win the prestigious Senescence Award years before you were a glint in your father's eye.
He is currently experimenting with age reversal in dogs using gene therapy that has been successful in mice, a technique he believes is the most promising of nine broad approaches to mortality and aging—genome stability, telomere extension, epigenetics, proteostasis, caloric restriction, mitochondrial research, cell senescence, stem cell exhaustion, and intercellular communication.
In addition to checking in periodically on Frank in his lonely senescence, the movie repeatedly jumps back to a fateful road trip he and Russell took with their wives (Stephanie Kurtzuba and Kathrine Narducci), a journey as intoxicated with the banality of midcentury, middle-class married life as a John Updike story.
The way it works inside the cell is not completely understood but it is thought to favourably influence metabolic and cellular processes associated with the development of age-related conditions such as inflammation, autophagy (when broken bits of cell are recycled) and cell senescence (when they are unable to grow and divide any longer).
The centerpiece is a 13-minute-long epic titled "The Everglades," which seems to chart the senescence of the Florida wetlands: It starts on a low lament, with open-tone electronics widening the space around his tolling piano, before the trio bursts into a driving fury — as brutal and uncontainable as the rising sea.
Supercentenarian Ann Pouder (8 April 1807 – 10 July 1917) photographed on her 110th birthday. A heavily lined face is common in human senescence. Senescence () or biological aging is the gradual deterioration of functional characteristics. The word senescence can refer either to cellular senescence or to senescence of the whole organism.
Johon Wiley & Sons Ltd. In addition, mutants that cannot perceive ethylene show delayed senescence. Genome-wide comparison of mRNAs expressed during dark-induced senescence versus those expressed during age-related developmental senescence demonstrate that jasmonic acid and ethylene are more important for dark-induced (stress-related) senescence while salicylic acid is more important for developmental senescence.
A confounding aspect of biological aging is the nature and role of senescent cells. It is unclear whether the three major types of cellular senescence, namely replicative senescence, oncogene-induced senescence and DNA damage-induced senescence are descriptions of the same phenomenon instigated by different sources, or if each of these is distinct, and how they are associated with epigenetic aging. Induction of replicative senescence (RS) and oncogene- induced senescence (OIS) were found to be accompanied by epigenetic aging of primary cells but senescence induced by DNA damage was not, even though RS and OIS activate the cellular DNA damage response pathway. These results highlight the independence of cellular senescence from epigenetic aging.
Unlike animals, plants continually form new organs and older organs undergo a highly regulated senescence program to maximize nutrient export. The autumn senescence of Oregon grape leaves is an example of programmed plant senescence.
Together with senescence-associated heterochromatin foci (SAHF), DNA-SCARS are one of the most prevalent nuclear markers of cellular senescence.
Cellular senescence limits fibrosis during wound closure by inducing cell cycle arrest in myofibroblasts once they have fulfilled their function. When these cells have accomplished these tasks, the immune system clears them away. This phenomenon is termed acute senescence. The negative implications of cellular senescence present themselves in the transition from acute to chronic senescence.
BRAFV600E and Ras are two oncogenes implicated in cellular senescence. BRAFV600E induces senescence through synthesis and secretion of IGFBP7. Ras activates the MAPK cascade which results in increased p53 activation and p16INK4a upregulation. The transition to a state of senescence due to oncogene mutations are irreversible and have been termed oncogene-induced senescence (OIS).
Senescence in cells is a state in which cells are metabolically active but are no longer able to replicate. Rb is an important regulator of senescence in cells and since this prevents proliferation, senescence is an important antitumor mechanism. Rb may occupy E2F-regulated promoters during senescence. For example, Rb was detected on the cyclin A and PCNA promoters in senescent cells.
Androgen deprivation-induced senescence (or ADIS) refers to the induction of cellular senescence as a result of androgen deprivation therapy.Barakat et al (2015). CCAAT/Enhancer binding protein β controls androgen-deprivation-induced senescence in prostate cancer cells Oncogene ADIS is observed in prostate cancer cells that are dependent on androgens for cell proliferation. Androgen withdrawal induces cells to undergo cellular senescence by up-regulating intracellular reactive oxygen species (ROS) that cause DNA damage.
Senescence-associated beta-galactosidase (SA-β-gal or SABG) is a hypothetical hydrolase enzyme that catalyzes the hydrolysis of β-galactosides into monosaccharides only in senescent cells. Senescence-associated beta- galactosidase, along with p16Ink4A, is regarded to be a biomarker of cellular senescence. Its existence was proposed in 1995 by Dimri et al. following the observation that when beta-galactosidase assays were carried out at pH 6.0, only cells in senescence state develop staining.
Concentrations of p16INK4a increase dramatically as tissue ages. p16INK4a, along with senescence- associated beta-galactosidase, is regarded to be a biomarker of cellular senescence. Therefore, p16INK4a could potentially be used as a blood test that measures how fast the body's tissues are aging at a molecular level. Notably, a recent survey of cellular senescence induced by multiple treatments to several cell lines does not identify p16 as belonging to a "core signature" of senescence markers.
Senescence can also be triggered by the presence of oncogenes or extracellular stress, but these mechanisms are not as well understood. The two main pathways that control the senescence response in most cells are the p53 and p16-pRB tumor suppressor pathways. As a transcription regulator, the p53 protein activates the transcription factor p21, which results in the transcription of proteins that result in cellular senescence. Research has shown that the pathway is primarily activated by stimuli that generate a DNA Damage Response, and therefore is a common pathway for telomere-dependent senescence as well as DNA-Damage initiated senescence.
The liver cancers that expressed Ras showed signs of senescence following p53 reactivation including an increase in senescence associated B-galactosidase protein. Even if the expression of p53 was transiently activated or deactivated, senescence via SA B-gal was observed. Xue et al. show that by briefly reactivating p53 in tumors without functional p53 activity, tumor regression is observed.
Depletion of NAD+ can lead to DNA damage and cellular senescence in vascular smooth muscle cells. Although senescent cells can no longer replicate, they remain metabolically active and commonly adopt an immunogenic phenotype consisting of a pro-inflammatory secretome, the up- regulation of immune ligands, a pro-survival response, promiscuous gene expression (pGE), and stain positive for senescence-associated β-galactosidase activity. Two proteins, senescence-associated beta-galactosidase and p16Ink4A, are regarded as biomarkers of cellular senescence. However, this results in a false positive for cells that naturally have these two proteins such as maturing tissue macrophages with senescence-associated beta-galactosidase and T-cells with p16Ink4A.
The relation of autogamy to senescence and rejuvenescence in Paramecium aurelia.
Cellular senescence is not observed in some organisms, including perennial plants, sponges, corals, and lobsters. In other organisms, where cellular senescence is observed, cells eventually become post-mitotic: they can no longer replicate themselves through the process of cellular mitosis (i.e., cells experience replicative senescence). How and why cells become post-mitotic in some species has been the subject of much research and speculation, but it has been suggested that cellular senescence evolved as a way to prevent the onset and spread of cancer.
The term gerontoplast was first introduced in 1977 to define the unique features of the plastid formed during leaf senescence. The process of senescence brings about regulated dismantling of cellular organelles involved in photosynthesis. Chloroplasts responsible for gas exchange in stomata are the last organelles to degrade during senescence, and give plants the green color. The formation of gerontoplasts from chloroplasts during senescence involves extensive structural modifications of the thylakoid membrane with the concomitant formation of a large number of plastoglobuli with lipophilic materials.
Programmed senescence seems to be heavily influenced by plant hormones. The hormones abscisic acid, Ethylene as a plant hormone#ethylene, jasmonic acid and salicylic acid are accepted by most scientists as promoters of senescence, but at least one source lists gibberellins, brassinosteroids and strigolactone as also being involved. Cytokinins help to maintain the plant cell and expression of cytokinin biosynthesis genes late in development prevents leaf senescence. A withdrawal of or inability of the cell to perceive cytokinin may cause it to undergo apoptosis or senescence.
Plant senescence is the process of aging in plants. Plants have both stress- induced and age-related developmental aging. Chlorophyll degradation during leaf senescence reveals the carotenoids, such as anthocyanin and xanthophylls and is the cause of autumn leaf color in deciduous trees. Leaf senescence has the important function of recycling nutrients, mostly nitrogen, to growing and storage organs of the plant.
LPSO live about two years. Like most octopus species, LPSO goes through a stage of senescence, which marks the approach of death. Senescence in LPSO has been observed to be longer for females and shorter for males. After the first signs of senescence, males will typically last 1 to 2 weeks before death, while females will typically last between 2 and 4 months.
Knock-down studies involving the chemokine receptor CXCR2 alleviates both replicative and oncogene-induced senescence (OIS) and diminishes the DNA-damage response. Also, ectopic expression of CXCR2 results in premature senescence via a p53-dependent mechanism.
Organismal senescence involves an increase in death rates and/or a decrease in fecundity with increasing age, at least in the latter part of an organism's life cycle. Senescence is the inevitable fate of all multicellular organisms with germ-soma separation, but it can be delayed. The discovery, in 1934, that calorie restriction can extend lifespan by 50% in rats, and the existence of species having negligible senescence and potentially immortal organisms such as Hydra, have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases.
This has crucial implications in cancer therapy; even though cancer cells are not contact-inhibited, confluent cancer cell cultures still suppress their senescence machinery. Therefore, this may be a plausible explanation why senescence-inducing cancer therapy drugs are ineffective.
Accessed 18 May 2020., and defining the roles of bioactive lipids in cell senescence Venable, Mark E., Joanna Y. Lee, Miriam J. Smyth, Alicja Bielawska, and Lina M. Obeid "Role of ceramide in cellular senescence" J. Biol. Chem., vol.
Not only does p16 play an important role in aging, but also in auto-immune diseases like rheumatoid arthritis that progressively lead to mobility impairment in advanced disease. In the nervous system, senescence has been described in astrocytes and microglia, but is less understood in neurons. Because senescence arrests cell division, studies of senescence in the brain were focused mainly on glial cells and less studies were focused on nondividing neurons.
It is important to recognize that cellular senescence is not inherently a negative phenomenon. During mammalian embryogenesis, programmed cellular senescence plays a role in tissue remodeling via macrophage infiltration and subsequent clearance of senescent cells. A study on the mesonephros and endolymphatic sac in mice highlighted the importance of cellular senescence for eventual morphogenesis of the embryonic kidney and the inner ear, respectively. They serve to direct tissue repair and regeneration.
Campisi and others theorize that cellular senescence directly promotes aging, but evidence remains largely circumstantial. The senescence response can be caused by a variety of factors. Telomere-dependent senescence is caused by the shortening of telomeres due to the end-replication problem of DNA replication. Dysfunctional telomeres trigger a classical DNA Damage Response, and are a major contributing factor to why many cells cannot replicate indefinitely without the presence of telomerase.
Research has shown that T-kininogen is a possible biomarker for senescence within rats.
Consistent with this, telomerase-immortalised cells continued to age (according to the epigenetic clock) without having been treated with any senescence inducers or DNA-damaging agents, re-affirming the independence of the process of epigenetic ageing from telomeres, cellular senescence, and the DNA damage response pathway. Although the uncoupling of senescence from cellular aging appears at first sight to be inconsistent with the fact that senescent cells contribute to the physical manifestation of organism ageing, as demonstrated by Baker et al., where removal of senescent cells slowed down aging. However, the epigenetic clock analysis of senescence suggests that cellular senescence is a state that cells are forced into as a result of external pressures such as DNA damage, ectopic oncogene expression and exhaustive proliferation of cells to replenish those eliminated by external/environmental factors.
The induction of cellular senescence was associated with an increase in inflammatory cytokines as is expected based on the SASP. The presence of both senescence and an increase in immune activity is able to regress and limit liver carcinoma growth in this mouse model.
This has served as the basis for all three modern theories for the evolution of senescence.
They suggested that the age related decline in expression of XRCC4 may contribute to cellular senescence.
These ERCs accumulate over time and eventually trigger replicative senescence and death of the mother cell.
Turtles, for example, were once thought to lack senescence, but more extensive observations have found evidence of decreasing fitness with age. Study of negligibly senescent animals may provide clues that lead to better understanding of the aging process and influence theories of aging. The phenomenon of negligible senescence in some animals is a traditional argument for attempting to achieve similar negligible senescence in humans by technological means. There are also organisms that exhibit negative senescence, whereby mortality chronologically decreases as the organism ages, for all or part of the life cycle, in disagreement with the Gompertz–Makeham law of mortality (see also Late-life mortality deceleration).
During leaf senescence, a portion of the plant's nutrients are reabsorbed from the leaves. The nutrient concentrations in litterfall differ from the nutrient concentrations in the mature foliage by the reabsorption of constituents during leaf senescence. Plants that grow in areas with low nutrient availability tend to produce litter with low nutrient concentrations, as a larger proportion of the available nutrients is reabsorbed. After senescence, the nutrient-enriched leaves become litterfall and settle on the soil below.
DNA-damage- initiated senescence is caused by major DNA damage (usually double-stranded breaks) that trigger pathways that keep the cell from dividing. As expected, both telomere-dependent and DNA-damage-initiated senescence have been shown to involve similar pathways.Herbig, U., Jobling, W. A., Chen, B. P., Chen, D. J. & Sedivy, J. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol. Cell 14, 501–513 (2004).
Mitochondrial depletion reduces a spectrum of senescence effectors and phenotypes while preserving ATP production via enhanced glycolysis.
One lineage then undergoes cellular senescence faster than the other. Natural selection can remove damaged cells and prevent their proliferation, counterbalancing the natural tendency for damaged cells to accumulate. However, some cells mutate in ways that escape these control mechanisms. Cancer cells avoid replicative senescence to become immortal.
Harris et al. found little evidence that, in humans, telomere length is a significant biomarker of normal aging with respect to important cognitive and physical abilities. Gilley and Blackburn tested whether cellular senescence in paramecium is caused by telomere shortening, and found that telomeres were not shortened during senescence.
Senescence is one of the main causes of floral color change along with induction by pollination. While angiosperm taxa show variation in the time that it takes senescence to occur, the mechanism is typically associated with the biosynthesis of anthocyanins. Evening primrose in the genus Oenothera are a common example of flowers that undergo color changes due to senescence. Oenothera will bloom in the evening and appear to be white or yellow, and by morning they fade to pink or orange.
Activation of the CDKN2A locus promotes the cellular senescence tumor suppressor mechanism, which is a permanent form of growth arrest. As senescent cells accumulate with aging, expression of CDKN2A increases exponentially with aging in all mammalian species tested to date, and has been argued to serve as a biomarker of physiological age. Notably, a recent survey of cellular senescence induced by multiple treatments to several cell lines does not identify CDKN2A as belonging to a "core signature" of senescence markers.
Senescence, together with apoptosis, may constitute a major mechanism of haemopoietic cell depletion occurred in bone marrow failure.
Inhibition of activity results in apoptosis. May contribute to tumorigenesis by suppressing p53/TP53-induced cancer cell senescence.
The process also enables cells to proceed to senescence, which are further stages of cell life and growth.
Ethylene's role in this developmental scenario is to move the plant away from a state of attracting pollinators, so it also aids in decreasing the production of these volatiles. Ethylene production in corolla tissue does not directly cause the senescence of corolla tissue, but acts by releasing secondary products that are consistent with tissue ageing. While the mechanism of ethylene-mediated senescence are unclear, its role as a senescence-directing hormone can be confirmed by ethylene-sensitive petunia response to ethylene knockdown. Knockdown of ethylene biosynthesis genes was consistent with increased corolla longevity; inversely, up-regulation of ethylene biosynthesis gene transcription factors were consistent with a more rapid senescence of the corolla.
Almost all animals who survive external hazards to their biological functioning eventually die from biological aging, known in life sciences as "senescence". Some organisms experience negligible senescence, even exhibiting biological immortality. These include the jellyfish Turritopsis dohrnii, the hydra, and the planarian. Unnatural causes of death include suicide and predation.
Senescence is distinct from quiescence because senescence is an irreversible state that cells enter in response to DNA damage or degradation that would make a cell's progeny nonviable. Such DNA damage can occur from telomere shortening over many cell divisions as well as reactive oxygen species (ROS) exposure, oncogene activation, and cell-cell fusion. While senescent cells can no longer replicate, they remain able to perform many normal cellular functions. Senescence is often a biochemical alternative to the self-destruction of such a damaged cell by apoptosis.
Activation of the ERK1/2 pathway by aberrant RAS/RAF signalling, DNA damage, and oxidative stress leads to cellular senescence. Low doses of DNA damage resulting from cancer therapy cause ERK1/2 to induce senescence, whereas higher doses of DNA damage fail to activate ERK1/2, and thus induce cell death by apoptosis.
The typical normal human fetal cell will divide between 50 and 70 times before experiencing senescence. As the cell divides, the telomeres on the ends of chromosomes shorten. The Hayflick limit is the limit on cell replication imposed by the shortening of telomeres with each division. This end stage is known as cellular senescence.
A new isoform for beta-galactosidase with optimum activity at pH 6.0 (Senescence Associated beta-gal or SA-beta-gal) which is specifically expressed in senescence (the irreversible growth arrest of cells). Specific quantitative assays were even developed for its detection. However, it is now known that this is due to an overexpression and accumulation of the lysosomal endogenous beta-galactosidase, and its expression is not required for senescence. Nevertheless, it remains the most widely used biomarker for senescent and aging cells, because it is reliable and easy to detect.
Senescent cells can undergo conversion to an immunogenic phenotype that enables them to be eliminated by the immune system. This phenotype consists of a pro-inflammatory secretome, the up-regulation of immune ligands, a pro-survival response, promiscuous gene expression (pGE) and stain positive for senescence-associated β-galactosidase activity. The nucleus of senescent cells is characterized by senescence-associated heterochromatin foci (SAHF) and DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS). Senescent cells affect tumour suppression, wound healing and possibly embryonic/placental development and a pathological role in age- related diseases.
Williams' 1957 paper Pleiotropy, Natural Selection, and the Evolution of Senescence is one of the most influential in 20th century evolutionary biology, and contains at least 3 foundational ideas. The central hypothesis of antagonistic pleiotropy remains the prevailing evolutionary explanation of senescence. In this paper Williams was also the first to propose that senescence should be generally synchronized by natural selection. According to this original formulation > if the adverse genic effects appeared earlier in one system than any other, > they would be removed by selection from that system more readily than from > any other.
Some tortoises show negligible senescence. Negligible senescence is a term coined by biogerontologist Caleb Finch to denote organisms that do not exhibit evidence of biological aging (senescence), such as measurable reductions in their reproductive capability, measurable functional decline, or rising death rates with age. There are many species where scientists have seen no increase in mortality after maturity. This may mean that the lifespan of the organism is so long that researchers' subjects have not yet lived up to the time when a measure of the species' longevity can be made.
In 1935, Crocker proposed that ethylene was the plant hormone responsible for fruit ripening as well as senescence of vegetative tissues.
117: 692-709.Boggs, Carol L. (January 2009). "Understanding insect life histories and senescence through a resource allocation lens". Functional Ecology.
Loss-of-function mutations or absence of Bub1 has been reported to result in aneuploidy, chromosomal instability (CIN) and premature senescence.
This reduction in the division and production of stem cells protects against cancer while increasing the risks associated with cellular senescence.
The Plant Journal. 28(2). 123-133, Besseau, Li and Palva (2012) WRKY54 and WRKY70 co-operate as negative regulators of leaf senescence in Arabidopsis thaliana. Journal of Experimental Botany. 63(7). 2667-2679, Miao and Zentgraf (2007) The Antagonist Function of Arabidopsis WRKY53 and ESR/ESP in Leaf Senescence Is Modulated by the Jasmonic and Salicylic Acid Equilibrium.
Menopause in the animal kingdom appears to be uncommon, but the presence of this phenomenon in different species has not been thoroughly researched. Life histories show a varying degree of senescence; rapid senescing organisms (e.g., Pacific salmon and annual plants) do not have a post-reproductive life-stage. Gradual senescence is exhibited by all placental mammalian life histories.
The word "post-mitotic" is sometimes used to refer to both quiescent and senescent cells. Cellular senescence occurs in response to DNA damage and external stress and usually constitutes an arrest in G1. Cellular senescence may make a cell's progeny nonviable; it is often a biochemical alternative to the self-destruction of such a damaged cell by apoptosis.
This loss of inhibition is one reason why telomere shortening causes senescence (Figure 1B). Future work in this area should involve clarifying the signaling pathway that connects checkpoint activation and senescence. For example, researchers should investigate the mechanism by which proteins involved in the DNA damage checkpoint pathway, such as p53, are activated by shortened telomeric ends.
Biotic Stress Resistance in Millets. Amsterdam: Academic, an Imprint of Elsevier, 2016. Print. Rough leaf spot can eventually lead to leaf senescence.
Irrespective of living standards, adaptive responses are limited by physiological mechanisms. In other words, senescence is programmed and regulated by specific genes.
Moreover, depletion of GAPDH has managed to induce senescence in tumor cells, thus presenting a novel therapeutic strategy for controlling tumor growth.
Senescence leads to reproduction and the process of rejuvenescence in each asexual cycle carries the organism back to the same stage of youth.
Chromatin architectural remodeling is implicated in the process of cellular senescence, which is related to, and yet distinct from, organismal aging. Replicative cellular senescence refers to a permanent cell cycle arrest where post-mitotic cells continue to exist as metabolically active cells but fail to proliferate. Senescence can arise due to age associated degradation, telomere attrition, progerias, pre-malignancies, and other forms of damage or disease. Senescent cells undergo distinct repressive phenotypic changes, potentially to prevent the proliferation of damaged or cancerous cells, with modified chromatin organization, fluctuations in remodeler abundance, and changes in epigenetic modifications.
In about 85% of tumors, this evasion of cellular senescence is the result of up-activation of their telomerase genes. In most multicellular species, somatic cells eventually experience replicative senescence and are unable to divide. This can prevent highly mutated cells from becoming cancerous. In culture, fibroblasts can reach a maximum of 50 cell divisions; this maximum is known as the Hayflick limit.
Autophagy is upregulated to promote survival. Considering cytokines, SASP molecules IL-6 and IL-8 are likely to cause senescence without affecting healthy neighbor cells. IL-1beta, unlike IL-6 or IL-8, is able to induce senescence in normal cells with paracrine signaling. IL-1beta is also dependent on cleavage of IL-1 by caspase-1, causing a pro-inflammatory response.
Mechanistically, replicative senescence can be triggered by a DNA damage response due to the shortening of telomeres. Cells can also be induced to senesce by DNA damage in response to elevated reactive oxygen species (ROS), activation of oncogenes, and cell-cell fusion. Normally, cell senescence is reached through a combination of a variety of factors (i.e., both telomere shortening and oxidative stress).
This is consistent with the fact that mice with naturally long telomeres still age and eventually die even though their telomere lengths are far longer than the critical limit, and they age prematurely when their telomeres are forcibly shortened, due to replicative senescence. Therefore, cellular senescence is a route by which cells exit prematurely from the natural course of cellular aging.
Sequestosome-1 is a protein that in humans is encoded by the SQSTM1 gene. Also known as the ubiquitin-binding protein p62, it is an autophagosome cargo protein that targets other proteins that bind to it for selective autophagy. By interacting with GATA4 and targeting it for degradation, it can inhibit GATA-4 associated senescence and senescence-associated secretory phenotype.
One of the goals of Campisi's research is the better balance the positive effects of cellular senescence, namely the powerful defense against cancer that the response provides, against the deleterious effects of the response, such as aging and the resulting decline in tissue function.Rodier, Francis, and Judith Campisi. "Four faces of cellular senescence." The Journal of cell biology (2011): jcb-201009094.
The term "negligible senescence" was first used in the early 1990s by professor Caleb Finch to describe organisms such as lobsters and hydras, which do not show symptoms of aging. The term "engineered negligible senescence" first appeared in print in Aubrey de Grey's 1999 book The Mitochondrial Free Radical Theory of Aging.de Grey, Aubrey (November 2003). The Mitochondrial Free Radical Theory of Aging.
These octopuses live one to two years. The end is signaled by egg-laying in the female and senescence in both males and females.
However, fetal membrane senescence can be accelerated by oxidative stress and hence, stimulate sterile inflammation to occur prior to term; consequently, causing preterm birth.
This has motivated researchers to develop senolytic drugs to kill and eliminate senescent cells to improve health in the elderly. The nucleus of senescent cells is characterized by senescence-associated heterochromatin foci (SAHF) and DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS). Senescent cells affect tumor suppression, wound healing and possibly embryonic/placental development, and play a pathological role in age-related diseases.
As such, the evidence suggests senescent cells can be associated with pre-malignant stages of the tumor. Further, it has been speculated that a senescent phenotype might serve as a promising marker for staging. There are two types of senescence in vitro. The irreversible senescence which is mediated by INK4a/Rb and p53 pathways and the reversible senescent phenotype which is mediated by p53.
A senolytic (from the words senescence and -lytic, "destroying") is among a class of small molecules under basic research to determine if they can selectively induce death of senescent cells and improve health in humans. A goal of this research is to discover or develop agents to delay, prevent, alleviate, or reverse age-related diseases. A related concept is "senostatic", which means to suppress senescence.
Mitochondrial ROS can promote cellular senescence and aging phenotypes in the skin of mice. Ordinarily mitochondrial SOD2 protects against mitochondrial ROS. Epidermal cells in mutant mice with a genetic SOD2 deficiency undergo cellular senescence, nuclear DNA damage, and irreversible arrest of proliferation in a portion of their keratinocytes. Mutant mice with a conditional deficiency for mitochondrial SOD2 in connective tissue have an accelerated aging phenotype.
More recent studies have also shown that in vivo activation of hepatic stellate cells by agents causing liver fibrosis can eventually lead to senescence in these cells, marked by increased SA-beta- galactosidase staining, as well as p53 accumulation and activation of Rb–hallmarks of cellular senescence. Senescent hepatic stellate cells have been demonstrated to limit liver fibrosis by activating interactions with NK cells.
Cockburn, A. "Living slow and dying young: senescence in marsupials." Marsupial Biology: Recent Research, New Perspectives. University of New South Wales Press, Sydney (1997): 163-171.
Bcl-w has been shown to contribute to cellular senescence. Quercetin has been shown to inhibit the PI3K/AKT pathway leading to downregulation of Bcl-w.
Although fantasy life can be understood through the examination of dreams, masturbation fantasiescf. Marcus, I. and J. Francis. 1975. Masturbation from Infancy to Senescence. are also important.
Faria has discussed how longevity in association with leading healthy lifestyles can lead to the postponement of senescence as well as happiness and wisdom in old age.
When up- regulated, Tbx2 inhibits p21CIP1. p21CIP1 is necessary for tissue senescence, and when compromised, leaves the tissue vulnerable to tumor-promoting signals. Wnt/beta-catenin Pathway.
Previous studies showed that LPE, a natural phospholipid, can accelerate ripening and prolong shelf life of tomato fruit,Farag KM, Palta JP, Physiol Plant. 87(1993) 515-521 and retard senescence in attached and detached leaves and fruit of tomato.Farag KM, Palta JP, Hort Technol, 3(1993) 62-65 In other studies, LPE inhibited the activity of phospholipase D (PLD), a membrane degrading enzyme, of which active is increased during senescence.
Ethylene shortens the shelf life of many fruits by hastening fruit ripening and floral senescence. Ethylene will shorten the shelf life of cut flowers and potted plants by accelerating floral senescence and floral abscission. Flowers and plants which are subjected to stress during shipping, handling, or storage produce ethylene causing a significant reduction in floral display. Flowers affected by ethylene include carnation, geranium, petunia, rose, and many others.
Reproductive improvement and senescence in a long-lived bird. PNAS:1-6 Despite senescence, birds that reach very old age have the highest life-time reproductive success. Physiological analyses of hormones and other blood parameters, as well as genetic analyses are also performed at this colony. Blood samples of breeding birds are taken without trapping, as this reduces stress, which could change blood parameters, for example by increasing stress hormones.
The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family.
Resorption involves degrading chlorophyll to extract the majority of its nutrients.Keskitalo, J., G. Bergguist, P. Gardestrom, and S. Jansson. 2005. A Cellular Timetable of Autumn Senescence. Plant Phys.
The optic glands are endocrine organs in the octopus and squid that play a role in sexual development and senescence. They lie between the brain and optic lobes.
It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence and aging, and inflammatory diseases such as Diabetes mellitus type 2 and rheumatoid arthritis.
Conversely, activation of p16 through reactive oxygen species, DNA damage, or senescence leads to the buildup of p16 in tissues and is implicated in the aging of cells.
These findings supports the idea that the senescence response is antagonistically pleiotropic, or that the response can be simultaneously beneficial and harmful to an organism's fitness. While the senescence response can be effective at protecting organisms from cancer at young ages, it can also cause the age-related decline in tissue function typical of many degenerative diseases in mammals. If the senescence response allowed an organism to be more likely to reach reproducing age while also being deleterious to the organism later in life, there would be little selective pressure to eliminate the harmful effects of the trait. This important concept may explain the development of aging in mammals from an evolutionary perspective.
In pathways that do not use p53 in inducing apoptosis, PML have been shown to interact with CHK2 and induce it to autophosphorylate to become active. In addition to those two apoptotic pathways, Fas-induced apoptosis relies on the PML-NBs to release FLICE-Associated huge protein, which then localizes to the mitochondria to promote the activation of Caspase-8. Beyond apoptosis, other studies have implicated PML-NBs in cellular senescence, particularly its induction. It has been shown to be involved with the formation of certain chromatin features of cells experiencing senescence, such as senescence-associated heterochromatin foci (SAHFs), which are believed to suppress the expression of growth-promoting factors and genes.
A microscopic sign of the pathogen are the stroma, mats of hyphae found in the lesions. These lesions can cause senescence of leaves but are mostly of cosmetic importance.
Under laboratory conditions, the larvae showed no signs of senescence at that point. According to some authorities, four years is long enough to drift completely across the Pacific Ocean.
It has been shown that the depletion of cGAS and STING in mouse embryonic fibroblasts and in primary human fibroblasts denies senescence and SASP (Senescent Associated Secreted Proteins) establishment.
The cellular senescence theory of aging posits that organismal aging is a consequence of the accumulation of less physiologically useful, i.e. senescent cells. In agreement with this, the experimental elimination of senescent cells from transgenic progeroid mice and non- progeroid, naturally-aged mice led to greater resistance against aging- associated diseases. Ectopic expression of the embryonic transcription factor, NANOG, is shown to reverse senescence and restore the proliferation and differentiation potential of senescent stem cells.
Hayflick's discovery of mortal cells paved the path for the discovery and understanding of cellular aging molecular pathways. Cellular senescence can be initiated by a wide variety of stress inducing factors. These stress factors include both environmental and internal damaging events, abnormal cellular growth, oxidative stress, autophagy factors, among many other things. The physiological importance for cell senescence has been attributed to prevention of carcinogenesis, and more recently, aging, development, and tissue repair.
These senescent cells, in sufficient numbers, will probably cause the deterioration of tissues, which is interpreted as organism ageing. However, at the cellular level, aging, as measured by the epigenetic clock, is distinct from senescence. It is an intrinsic mechanism that exists from the birth of the cell and continues. This implies that if cells are not shunted into senescence by the external pressures described above, they would still continue to age.
August 10, 2001 In the news: Antinori and Zavos In Aubrey de Grey's proposed SENS (Strategies for Engineered Negligible Senescence), one of the considered options to repair the cell depletion related to cellular senescence is to grow replacement tissues from stem cells harvested from a cloned embryo.de Grey, Aubrey; Rae, Michael (September 2007). Ending Aging: The Rejuvenation Breakthroughs that Could Reverse Human Aging in Our Lifetime. New York, NY: St. Martin's Press, 416 pp. .
From all causes, roughly 150,000 people die around the world each day. Of these, two thirds die directly or indirectly due to senescence, but in industrialized countries – such as the United States, the United Kingdom, and Germany – the rate approaches 90% (i.e., nearly nine out of ten of all deaths are related to senescence). Physiological death is now seen as a process, more than an event: conditions once considered indicative of death are now reversible.
It is estimated that of the roughly 150,000 people who die each day across the globe, about two thirds—100,000 per day—die of age-related causes. In industrialized nations the proportion is much higher, reaching 90 percent. Thus, albeit indirectly, biological aging (senescence) is by far the leading cause of death. Whether senescence as a biological process itself can be slowed, halted, or even reversed is a subject of current scientific speculation and research.
They have a limited number of divisions before the cells become unable to divide (senescence), or die (crisis). The cause of these barriers is primarily due to the DNA at the end of chromosomes, known as telomeres. Telomeric DNA shortens with every cell division, until it becomes so short it activates senescence, so the cell stops dividing. Cancer cells bypass this barrier by manipulating enzymes (telomerase) to increase the length of telomeres.
Additionally, upregulating histone deacetylases, such as members of the sirtuin family, can delay senescence by removing acetyl groups that contribute to greater chromatin accessibility. General loss of methylation, combined with the addition of acetyl groups results in a more accessible chromatin conformation with a propensity towards disorganization when compared to mitotically active cells. General loss of histones precludes addition of histone modifications and contributes changes in enrichment in some chromatin regions during senescence.
They are involved in modulating senescence of organs in plants and are therefore considered as a plant hormone. In addition, they are directly involved in regulation of programmed cell death.
Polycomb group proteins have also been shown to affect DNA damage and apoptosis pathways preventing cells from entering senescence; this is a state in which the cell ceases to replicate.
Monaghan's research interests are in behavioural ecology, avian ecology, ornithology, molecular ecology and senescence. She has served as president of Association for the Study of Animal Behaviour (ASAB) since 2017.
Innovative Food Science and Emerging Technologies, 20, 1–15. It is traditionally used on horticultural products to prevent sprouting and post- packaging contamination, delay post-harvest ripening, maturation and senescence.
The overall amount of free haemocyte within S. monstrosus has been found to decrease as they age, possibly thought to trigger senescence due to the creation of abnormalities within the insect.
She is listed in Who's Who in Gerontology. She is widely known for her research on how senescent cells influence aging and cancer — in particular the Senescence Associated Secretory Phenotype (SASP).
As a cyclin-dependent kinase inhibitor (CDKI), p16 works by down-regulating molecules that keep pRB in an active, hypophosphorylated form. This, in turn, keeps E2F from transcribing genes that are needed for cellular proliferation. The p16-pRB pathway can be activated by the DNA Damage Response, but is usually secondary to the p53 response in such cases.Jacobs, J. J. & de Lange, T. Significant role for p16(INK4a) in p53-independent telomere-directed senescence. Curr. Biol. 14, 2302–2308 (2004). The p16-pRB pathway has instead been shown to primarily be active in other senescence-inducing pathways, especially in epithelial cells.Vijayachandra, K., Lee, J. & Glick, A. B. Smad3 regulates senescence and malignant conversion in a mouse multistage skin carcinogenesis model. Cancer Res. 63, 3447–3452 (2003).
This represses the transcriptional targets of E2F1, leading to cell cycle arrest after the G1 phase. p16Ink4a also activates pRB, but through inactivation of cyclin-dependent kinase 4 (Cdk 4) and cyclin- dependent kinase 6 (Cdk 6). p16Ink4a is responsible for the induction of premature, stress-induced senescence. This is not irreversible; silencing of p16Ink4a through promotor methylation or deletion of the p16Ink4a locus allows the cell to resume the cell cycle if senescence was initiated by p16Ink4a activation.
Cells respond to stress in the form of DNA damage, activated oncogenes, or sub-par growing conditions, and can enter a senescence-like state called "premature senescence". This allows the cell to prevent further replication during periods of damaged DNA or general unfavorable conditions. DNA damage in a cell can induce Rb activation. Rb's role in repressing the transcription of cell cycle progression genes leads to the S phase arrest that prevents replication of damaged DNA.
Some genets have been reported to be many thousands of years old, and a steady rate of branching likely aids in avoiding senescence. The oldest reported minimum age of a single genet is 43,600 years, for Lomatia tasmanica W.M.Curtis. It is hypothesized that some perennial plants even display negative senescence, in which their fecundity and survival increase with age. Examples of plants with rhizomatous growth include perennial Sorghum and rice, which likely share similar underlying genes controlling rhizome growth.
During normal body activities, cells divide, grow and differentiate into different cell types and serve different functions. The above procedures are also known as senescence. After senescence, body cells would start to become old, and several functions would be lost during the process. As these cells with limited functions are inefficient in performing body activities, they are programmed to self demolition under the presence of apoptotic signals, such as caspase proteins and Bcl-2 family regulation proteins.
Faria claims that postponement of senescence as well as happiness and wisdom can be attained in old age in a large proportion of those who lead healthy lifestyles and remain intellectually active.
The fact that hair loss is cumulative with age while androgen levels fall as well as the fact that finasteride does not reverse advanced stages of androgenetic alopecia remains a mystery but some possible explanations have been put forward: Higher conversion of testosterone to DHT locally with age as higher levels of 5-alpha reductase are noted in balding scalp, and higher levels of DNA damage in the dermal papilla as well as senescence of the dermal papilla due to androgen receptor activation and environmental stress. The mechanism by which the androgen receptor triggers dermal papilla permanent senescence is not known but may involve IL6, TGFB-1 and oxidative stress. Senescence of the dermal papilla is measured by lack of mobility, different size and shape, lower replication and altered output of molecules and different expression of markers. The dermal papilla is the primary location of androgen action and its migration towards the hair bulge and subsequent signaling and size increase are required to maintain the hair follicle so senescence via the androgen receptor explains much of the physiology.
Some plesiosaur fossils show pathologies, the result of illness or old age. In 2012, a mandible of Pliosaurus was described with a jaw joint clearly afflicted by arthritis, a typical sign of senescence.
Long-term growth of diploid human fibroblasts in low serum media. Experimental gerontology 25, 97-105.Wistrom, C., and Villeponteau, B. (1992). Cloning and expression of SAG: a novel marker of cellular senescence.
Depending on the severity of the DNA damage, the cells may no longer be able to undergo repair and either go through apoptosis or cell senescence. Such senescent cells in mammalian culture and tissues retain DSBs and DDR markers. It has been proposed that retained DSBs are major drivers of the aging process. Mutations in genes relating to genome maintenance has been linked with premature aging diseases, supporting the role of cell senescence in aging (see DNA damage theory of aging).
Much of Campisi's work focuses on the complex relationship between cellular senescence, aging and cancer. Her research is leading to new discoveries in anti-cancer genes, DNA repair mechanisms, molecular pathways that protect cells against stress, and the role of stem cells in aging and age-related disease. Cellular senescence was first formally observed in 1965 by Leonard Hayflick, who demonstrated that certain cells have limited ability to proliferate in- vitro.Hayflick, L. The limited in vitro lifetime of human diploid cell strains. Exp.
CYR61 also accelerates and promotes the chondrogenic differentiation of mouse limb bud mesenchymal cells, and stimulates osteoblast differentiation but inhibits osteoclastogenesis. Cyr61 is a strong inducer of reactive oxygen species accumulation in fibroblastic cells, and this activity underlies many CYR61-induced apoptosis and senescence. CYR61 is able to support cell adhesion, stimulate cell migration, promote growth factor-induced cell proliferation and differentiation in some cell types, promote apoptosis in synergy with TNF family cytokines, and induce cellular senescence in fibroblasts.
Aging (senescence) increases vulnerability to age-associated diseases, whereas genetics determines vulnerability or resistance between species and individuals within species. Some age-related changes (like graying hair) are said to be unrelated to an increase in mortality. But some biogerontologists believe that the same underlying changes that cause graying hair also increase mortality in other organ systems and that understanding the incidence of age-associated disease will advance knowledge of the biology of senescence just as knowledge of childhood diseases advanced knowledge of human development. Strategies for Engineered Negligible Senescence (SENS) is a research strategy which aims to repair a few "root causes" for age-related illness and degeneration, as well as develop medical procedures to periodically repair all such damage in the human body, thereby maintaining a youth-like state indefinitely.
In cellular senescence, ATM and ATR inhibit p62, an autophagy adaptor responsible for selective autophagy of GATA4. Inhibition of p62 leads to increased GATA4 levels, resulting in NF-kB activation and subsequent SASP induction.
Biochimica et Biophysica Acta 1130, 253-258.Pikaart, M., Irving, J., and Villeponteau, B. (1991). Decline in histone H5 phosphorylation during erythroid senescence in chick embryos. Mechanisms of ageing and development 59, 189-195.
Cell Res. 37, 614–636 (1965). After several replications, certain cells can lose their ability to divide, but still remain functionally viable. These phenomena became known as cellular senescence, and could be viewed as both helpful and harmful to an organism; it could be helpful in a sense that the senescence could act as a powerful tumor-suppressive mechanism, but harmful in the sense that it could result in the accumulation of non- dividing cells in healthy tissues which could lead to impaired regenerative capacity and function.
SEER Incidence Rates, 2003–2007 An aging-associated disease is a disease that is most often seen with increasing frequency with increasing senescence. Essentially, aging-associated diseases are complications arising from senescence. Age-associated diseases are to be distinguished from the aging process itself because all adult animals age, save for a few rare exceptions, but not all adult animals experience all age-associated diseases. Aging- associated diseases do not refer to age-specific diseases, such as the childhood diseases chicken pox and measles.
Thus, they can divide indefinitely, without initiating senescence. Mammalian cells have an intrinsic program, the Hayflick limit, that limits their multiplication to about 60–70 doublings, at which point they reach a stage of senescence. This limit can be overcome by disabling their pRB and p53 tumor suppressor proteins, which allows them to continue doubling until they reach a stage called crisis, with apoptosis, karyotypic disarray, and the occasional (10−7) emergence of an immortalized cell that can double without limit. Most tumor cells are immortalized.
The field of biodemography often explores the scientific questions associated with fertility and mortality across cultures, the determinants of reproductive senescence, mortality and sex differences, low fertility in humans, and longer post-reproductive lifespan in women.
Indeed, TBX3 interacts with Coactivator of AP1 and Estrogen Receptor (CAPERα) to repress the long non-coding RNA, Urothelial Cancer Associated 1 (UCA1), which leads to the bypass of senescence through the stabilization of p16INK4a mRNA.
The disease is thought to be caused by mutations in the DNA damage response, telomere shortening, or a combination of the two. Progeroid syndromes are all examples of aging diseases where cell senescence appears to be implicated.
Cultures not containing telomerase-active pluripotent stem cells would have been populated with telomerase-inactive cells, which would have been subject to the 50 ± 10 mitosis event limit until cellular senescence occurs as described in Hayflick's findings.
This study showed the effect of Colostrinin on the mitochondria of cells isolated from strains of senescence- prone (SAMP1) and senescence-resistant (SAMR1) mice. The data showed that cells from SAMP1 mice produce more reactive oxygen species (ROS), exhibit severe mitochondrial dysfunction, and have a decreased lifespan compared to the cells from SAMR1 mice. Addition of Colostrinin to SAMP1 cells significantly decreased ROS levels, normalized mitochondrial function and increased the lifespan to levels similar to those in SAMR1 cells. This in- vitro effect was followed up in actual mice as well.
Transplantation of only a few (1 per 10,000) senescent cells into lean middle- aged mice was shown to be sufficient to induce frailty, early onset of aging- associated diseases, and premature death. Biomarkers of cellular senescence have been shown to accumulate in tissues of older individuals. The accumulation of senescent cells in tissues of vertebrates with age is thought to contribute to the development of ageing-related diseases, including Alzheimer's disease, Amyotrophic lateral sclerosis, type 2 diabetes, and various cancers. Progeria is another example of a disease that may be related to cell senescence.
Thus, contact inhibition of proliferation may be viewed as a reversible form of cell cycle arrest. Furthermore, to transition from cell cycle arrest to senescence, contact-inhibited cells must activate growth- activating pathways such as mTOR. Once cells in high-density cultures become confluent enough such that the cell area falls below a critical value, the adhesion formations trigger pathways that downregulate mitogen signaling and cell proliferation. The growth-promoting mTOR pathway is therefore inhibited, and consequently the contact-inhibited cells cannot transition from cell cycle arrest to senescence.
The exact cause of primary sclerosing cholangitis is unknown and its pathogenesis is poorly understood. Although PSC is thought to be caused by autoimmune disease, it does not demonstrate a clear response to immunosuppressants. Thus, many experts believe it to be a complex, multifactorial (including immune-mediated) disorder and perhaps one that encompasses several different hepatobiliary diseases. Data have provided novel insights suggesting: # an important association between the intestinal microbiota and PSC and # a process referred to as cellular senescence and the senescence-associated secretory phenotype (SASP) in the pathogenesis of PSC.
The ZSCAN4 gene encodes a protein involved in telomere maintenance and with a key role in the critical feature of mouse embryonic stem cells, namely, defying cellular senescence and maintaining normal karyotype for many cell divisions in culture.
The journal covers research on genes and functional genomics, cell proliferation, senescence and death, stem cells and aging, signaling and gene expression, cell stress and damage, integrative physiology, etc. The journal publishes research articles, reviews, minireviews and commentaries.
There is much optimism; however, it appears that researchers still have a long way to go before they are able to understand how the results of their work might apply to the reduction or elimination of human senescence.
NSF affects males and females in approximately equal numbers and has been reported in patients of different ethnic and geographic regions. It most often affects middle-aged individuals, but there are reports of cases occurring from childhood to senescence.
Storage is in the form of non-labile soil organic carbon (SOC), which is part of the soil organic matter (SOM) pools. SOM pools are also increased by leaves’ senescence, and by animals returning undigested fibre to the soil.
Unregulated cell division can lead to the formation of a tumor (see cancer), which is potentially lethal to an organism. Therefore, the induction of senescence and apoptosis is considered to be part of a strategy of protection against cancer.
It is usually the result of harvesting or handling injuries. Ripening occurs when a fruit is mature. Ripeness is followed by senescence and breakdown of the fruit. The category “fruit” refers also to products such as aubergine, sweet pepper and tomato.
Two genetically modified crops have been approved for food use in some countries, but have not obtained approval for cultivation. A GM Melon engineered for delayed senescence was approved in 1999 and a herbicide tolerant GM wheat was approved in 2004.
This is refuted by neurosurgeon and medical ethicist Miguel Faria, who in two articles in Surgical Neurology International claims that healthy lifestyles and brain plasticity can lead to the postponement of senescence and lead to happiness even as we age.
The fruit is a nut, its surface densely covered in hairs. These small nuts are packed together within the dried inflorescence, which remains on the plant after senescence. When eventually released, the seeds are dispersed by means of the wind.
For example, CYR61 induces angiogenic functions in endothelial cells through αvβ3, and in fibroblasts promotes cellular senescence and enables TNFα to induce apoptosis through binding to α6β1-HSPGs. However, CYR61 supports cell adhesion through all of the integrins identified above.
Journal of Animal Ecology 75: 777-788. Finally, Eriogonum plants go into senescence after 10–15 years. This poses a significant problem for habitat maintenance, and suggests a need for regular dispersal of new Eriogonum plants as part of conservation efforts.
An altered repertoire of fos/jun (AP-1) at the onset of replicative senescence. Experimental cell research 202, 161-166.Feng, J., and Villeponteau, B. (1992). High-resolution analysis of c-fos chromatin accessibility using a novel DNase I-PCR assay.
In 1997 Villeponteau proposed the Heterochromatin Loss Model Of Aging, which proposed that the epigenetics of heterochromatin structure plays an important role in aging. Heterchromatin is a repressor of gene expression and its loss leads to inappropriate gene expression with senescence.
The BIR pathway can also help to maintain the length of telomeres (regions of DNA at the end of eukaryotic chromosomes) in the absence of (or in cooperation with) telomerase. Without working copies of the enzyme telomerase, telomeres typically shorten with each cycle of mitosis, which eventually blocks cell division and leads to senescence. In budding yeast cells where telomerase has been inactivated through mutations, two types of "survivor" cells have been observed to avoid senescence longer than expected by elongating their telomeres through BIR pathways. Maintaining telomere length is critical for cell immortalization, a key feature of cancer.
Senescence is associated with the aging of actively cycling and dividing cells. As the fetal membrane cells proliferate during remodelling, the telomeres (short length or non-coding DNA on the end of chromosomes that protect essential coding DNA from degradation during replication) shorten as chromosomes can not be copied end-to-end fully. Once the telomeres have reached a critical length the cell can no longer divide and can hence cause telomere-dependent replicative senescence. This should occur naturally at term (37 weeks), as it is an important factor to increase the inflammatory environment in the uterus to initiate parturition.
In other words, natural selection will always be in greatest > opposition to the decline of the most senescence-prone system. This important concept of synchrony of senescence was taken up a short time later by John Maynard Smith, and the origin of the idea is often misattributed to him, including in his obituary in the journal Nature. Finally, Williams' 1957 paper was the first to outline the "grandmother hypothesis". William's formulation stated that natural selection might select for menopause and post- reproductive life in females (though not explicitly mentioning grandchildren or the inclusive fitness contribution of grand-parenting).
Strategies for Engineered Negligible Senescence (SENS) is the term coined by British biogerontologist Aubrey de Grey for the diverse range of regenerative medical therapies, either planned or currently in development, for the periodical repair of all age-related damage to human tissue with the ultimate purpose of maintaining a state of negligible senescence in the patient, thereby postponing age-associated disease for as long as the therapies are reapplied.de Grey, Aubrey; Rae, Michael (September 2007). Ending Aging: The Rejuvenation Breakthroughs that Could Reverse Human Aging in Our Lifetime. New York, NY: St. Martin's Press, 416 pp. .
This discovery of the role of SLs in shoot branching led to a dramatic increase in the interest in these hormones, and it has since been shown that SLs play important roles in leaf senescence, phosphate starvation response, salt tolerance, and light signalling.
Given the facts that MARCH5 regulates the protein proteostasis of Drp1, mitofusin 1, and mitofusin 2 that are pivotal regulators of mitochondrial fusion and fission, MARCH5 is critical for the regulation of standard mitochondria morphology, and deficiencies in it promote cellular senescence.
Caterpillars of tea loopers are minor pests of many cultivated crops. Infected plants show symptoms similar to Ectropis bhurmitra. Leaves are bored and sometimes cut along the margins in a characteristic way. Damage from late instars show heavy dieback and complete leaf senescence.
This virus causes narrow greenish-purple streaks that turn white to yellow, on the leaves and flower stalk after flowering, and premature senescence, which reduces bulb size and yields."Narcissus (Narcissus spp.)". UC Pest Management Guidelines. Agriculture and Natural Resources, University of California.
FIS1 also prevents mitochondria elongation, which would otherwise lead to cell cycle delay or arrest, and ultimately, senescence. Moreover, mitochondrial dysfunction results in elevated reactive oxygen species (ROS) levels, which cause DNA damage and induce transcriptional repression, as well as induce mitophagy.
Replicative senescence is the result of telomere shortening that ultimately triggers a DNA damage response. Cells can also be induced to senesce via DNA damage in response to elevated reactive oxygen species (ROS), activation of oncogenes and cell-cell fusion, independent of telomere length.
Planting of infected seeds may result in seedlings with foot rot. Severe infection may kill or stunt young plants and in mature plants, it is likely to cause senescence of all lower leaves and blackening of the stems at the base of the plants.
T-kininogen (TK) is only found in rats and a protein whose function is still being researched. TK is believed to be a biological indicator of senescence in rats, which can be measured by the level of endothelial cell production during the aging process.
They found that the spore-like bodies would grow into a larger, spherical organism, encircled by the ring described above. Then, divisions form radiating from the center, and a stipe grows and releases a spore. After about 10 days, the organism degenerates and dies (senescence).
They can shorten telomeres, repetitive nucleotide sequences at the end of chromosomes, which accelerates cell destruction. Gerontogens can also accelerate the rate of cellular senescence, where normal diploid cells cease to divide. This can be measured using the body's levels of the protein p16.
Knowing this, Williams argued that if only close linkage was present, then beneficial traits will occur both before and after reproduction due to natural selection. This, however, is not observed in nature, and thus antagonistic pleiotropy contributes to the slow deterioration with age (senescence).
By extension of this fact, Skp2 inactivation profoundly restricts cancer development by triggering a massive cellular senescence and/or apoptosis response that is surprisingly observed only in oncogenic conditions in vivo. This response is triggered in a p19Arf/p53-independent, but p27-dependent manner. Using a Skp2 knockout mouse model, multiple groups have shown Skp2 is required for cancer development in different conditions of tumor promotion, including PTEN, ARF, pRB in activation as well as Her2/Neu overexpression. Genetic approaches have demonstrated that Skp2 deficiency inhibits cancer development in multiple mouse models by inducing p53-independent cellular senescence and blocking Akt- mediated aerobic glycolysis.
Some fish, such as some varieties of sturgeon and rougheye rockfish, and some tortoises and turtles are thought to be negligibly senescent, although recent research on turtles has uncovered evidence of senescence in the wild. The age of a captured fish specimen can be measured by examining growth patterns similar to tree rings on the otoliths (parts of motion-sensing organs). In 2018, naked mole-rats were identified as the first mammal to defy the Gompertz–Makeham law of mortality, and achieve negligible senescence. It has been speculated however that this may be simply a "time- stretching" effect primarily due to their very slow (and cold-blooded and hypoxic) metabolism.
The reproductive system is observed to remain intact, and even the gonads of the Turritopsis dohrnii are existing. Some species exhibit "negative senescence", in which reproduction capability increases or is stable, and mortality falls with age, resulting from the advantages of increased body size during aging.
Senescence-associated secretory phenotype (SASP) gene expression is induced by a number of transcription factors, including C/EBPβ, of which the most important is NF-κB. Aberrant oncogenes, DNA damage, and oxidative stress induce mitogen-activated protein kinases, which are the upstream regulators of NF-κB.
The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. Alternatively spliced transcript variants of this gene have been reported but their full-length nature has not been determined.
The seeds are stored in the many caps (fruits) in the dried, fire-resistant seed head, which is itself retained on the plant after senescence. The fruits are woody and persistent. The seeds are released from the caps after wildfires and dispersed by means of the wind.
Cycloastragenol is a molecule isolated from various species in the genus Astragalus that is purported to have telomerase activation activity. A preliminary in vitro study on human CD4 and CD8 T cells found that cycloastragenol may moderately increase telomerase activity and inhibit the onset of cellular senescence.
While trapped inside the flower, the fly eats nectar produced along the walls of the utricle. The trichomes then are signaled to wither, allowing for the fly to escape. The entire reproductive process lasts two days before flower senescence and abscission occur in the third phase.
TFs such as NAC (composed of NAM, ATAF, and CUC), are also related to drought response in Arabidopsis and rice. Overexpression in the aforementioned plants improves stress and drought tolerance. They also may be related to root growth and senescence, two physiological traits related to drought tolerance.
Furthermore, there are species that have been observed to regress to a larval state and regrow into adults multiple times, such as Turritopsis dohrnii. Studies have indicated a connection between phenomena related to negligible senescence and the general stability of an organism's genome over its lifetime.
This is most important disease in non-tradition wheat growing areas. The B. sorokiniana comes with Pyrenophora tritici-repentis and causes millions of tons of wheat loss each year. The symptoms are blotch as well as induced senescence due to premature chlorophyll losses Rosyara et al., 2007.
The larvae are 110–130 mm long. Early instars feed on the surface of the petiole, scratching the epidermis and then perforating the interior. They create sinuous tunnels with irregular borders. These interrupt the flow of water and nutrients, causing premature senescence of the flowers or fruits.
The potential new child requires the parent to modify their behavior to accommodate a new member of the family. Come senescence and retirement, behavior is more stable as the individual has often established their social circle (whatever it may be) and is more committed to their social structure.
H. vulgaris is often used, like many hydra, as a model organism for morphallactic regeneration because they are easy to care for, requiring minimal direct care, and reproduce relatively quickly. It is reported that they do not undergo senescence, making them biologically immortal although this has been disputed.
The function of macroH2A has generally been assumed to be transcriptional silencing; most recently, it has been suggested that macroH2A is important in repressing transcription at Senescence-Associated Heterochromatin Foci (SAHF). Chromatin that contains macroH2A is impervious to ATP-dependent remodeling proteins and to the binding of transcription factors.
Caulobacter was the first asymmetric bacterium shown to age. Reproductive senescence was measured as the decline in the number of progeny produced over time. On the basis of experimental evolution studies in C. crescentus, Ackermann et al. suggested that aging is probably a fundamental property of all cellular organisms.
The protein encoded by this intronless gene is a member of the JUN family, and a functional component of the AP1 transcription factor complex. It has been proposed to protect cells from p53-dependent senescence and apoptosis. Alternate translation initiation site usage results in the production of different isoforms.
Another recent discovery were inhibitors of the Skp1/Skp2 interface that resulted in: restoring p27 levels, suppressing survival, trigger p53-independent senescence, exhibit potent antitumor activity in multiple animal models, and were also found to affect Akt-mediated glycolysis. Skp2 is a potential target for pten-deficient cancers.
Thus P16 participates not only in the initiation but also in the maintenance of cellular senescence, as well in tumor suppression. On the other hand, some specific tumors harbor high levels of P16, and its function in limitation of tumorigenic progression has been inactivated via the loss of Rb.
There are two primary tumor suppressor pathways known to mediate senescence: ARF/p53 and INK4A/RB. More specifically p16INK4a-pRb tumor suppressor and p53 are known effectors of senescence. Most cancer cells have a mutated p53 and p16INK4a-pRb, which allows the cancer cells to escape a senescent fate. The p16 protein is a cyclin dependent kinase inhibitor (CDK) inhibitor and it activates Rb tumor suppressor. p16 binds to CDK 4/6 to inhibit the kinase activity and inhibit Rb tumor suppressor via phosphorylation. The Rb tumor suppressor has been shown to associate with E2F1 (a protein necessary for transcription) in its monophosphorylated form, which inhibits transcription of downstream target genes involved in the G1/S transition.
Senescence, an irreversible process in which the cell no longer divides, is a protective response to the shortening of the chromosome ends. The telomeres are long regions of repetitive noncoding DNA that cap chromosomes and undergo partial degradation each time a cell undergoes division (see Hayflick limit). In contrast, quiescence is a reversible state of cellular dormancy that is unrelated to genome damage (see cell cycle). Senescence in cells may serve as a functional alternative to apoptosis in cases where the physical presence of a cell for spatial reasons is required by the organism, which serves as a "last resort" mechanism to prevent a cell with damaged DNA from replicating inappropriately in the absence of pro-growth cellular signaling.
The fruits ripen after some seven months. The fruits are woody and persistent, which means they are retained on the plant after senescence. The seed is kept within the dry fruit for several years, and when finally released after the plant burns and dies. This is known as fire-mediated serotiny.
The fruit is a nut. The seed is stored in a capsule which is retained in the dried, fire-resistant inflorescence, which itself remains attached to the plant after senescence. When they are eventually released after fires stimulate the capsules to open, the seeds are dispersed by means of the wind.
Physical development in midlife and beyond include changes at the biological level (senescence) and larger organ and musculoskeletal levels. Sensory changes and degeneration begin to be common in midlife. Degeneration can include the break down of muscle, bones, and joints. Which leads to physical ailments such as sarcopenia or arthritis.
One of the main criticisms of the free radical theory of aging is directed at the suggestion that free radicals are responsible for the damage of biomolecules, thus being a major reason for cellular senescence and organismal aging. Several modifications have been proposed to integrate current research into the overall theory.
Alucard is not immortal (he himself has said "There is no such thing as immortals") but he does not age. In reality, Alucard's lack of senescence comes from the number of humans whose blood he consumed over the ages, which is a number in the millions.Hirano, Kohta (2007). Hellsing, Volume 4.
Aptx−/− mutant mice have been generated, but they lack an obvious phenotype. Another mouse model was generated in which a mutation of superoxide dismutase I (SOD1) is expressed in an Aptx−/− mouse. The SOD1 mutation causes a reduction in transcription recovery following oxidative stress. These mice showed accelerated cellular senescence.
Caenorhabditis elegans, which progresses through a series of larval stages into a final reproductive adult, may instead enter a less metabolically active dauer diapause stage if food scarcity or overcrowding occurs before reaching adulthood. Disabling DAF-2 arrests development in the dauer stage which increases longevity, delays senescence and prevents reproductive maturity.
In low concentrations, auxin can inhibit ethylene formation and transport of precursor in plants; however, high concentrations can induce the synthesis of ethylene. Therefore, the high concentration can induce femaleness of flowers in some species. Auxin inhibits abscission prior to the formation of the abscission layer, and thus inhibits senescence of leaves.
Sierra Sciences, LLC is a biotechnology company founded by William H. Andrews, former director of molecular biology at Geron Corporation. Andrews founded Sierra Sciences in 1999 in Reno, Nevada with the goal of preventing and/or reversing cellular senescence, and ultimately curing diseases associated with human aging, including the aging process itself.
In addition to senescence pattern, resource availability and density also matter in regulation of guppy populations. Guppies reduce their fecundity and reproductive allocation in response to scarce food. When food is abundant, they increase brood size. Differential reproductive allocation can be the cause of seasonality of life-history characteristics in some guppy populations.
The seed is stored in a capsule which is held within the woody, dried, fire-resistant inflorescence, which is itself retained on the plant after senescence ('persistent'). The seeds are released one to two years after flowering, after wildfires cause the fruits to open. Seeds are dispersed through means of the wind.
Egg production can start when the animals reach about 15 mm in length. Egg production increases with ctenophore size, and it is unclear when senescence occurs. It has a transient anus, which means that it appears only during defecation. There is no permanent connection between the gut and the rear of the body.
Besides the culture of well-established immortalised cell lines, cells from primary explants of a plethora of organisms can be cultured for a limited period of time before senescence occurs (see Hayflick's limit). Cultured primary cells have been extensively used in research, as is the case of fish keratocytes in cell migration studies.
In most plastid-containing species, glutamyl-tRNA is encoded by a plastid gene, and the transcription, as well as the following steps of C5 pathway, take place in plastids.Biswal, Basanti; Krupinska, Karin; Biswal, Udaya, eds. (2013). Plastid Development in Leaves during Growth and Senescence (Advances in Photosynthesis and Respiration). Dordrecht: Springer. p. 508.
Normal cells have apoptotic proteins that will respond to an overstimulation of mitogenic signaling pathways by triggering cell death or senescence. This generally prevents the onset of cancer from a single oncogenic mutation. In tumor cells, there is generally another mutation that inhibits apoptotic proteins as well, suppressing the hyperproliferation stress response.
Citrin develops strategies to enhance the capacity of radiation to kill tumor cells while protecting normal tissue from the side effects of radiation treatment. Her laboratory work focuses on aging in tissue exposed to radiation through stem cell senescence. She is board certified by the American Board of Radiology. Citrin has 3 children.
Taphrina entomospora is a fungal plant pathogen that infects the leaves of Nothofagus. T. entomospora infection results in chlorosis and changes in parenchyma structure of the leaf causing premature senescence. The species was first described scientifically by mycologist Roland Thaxter in 1910. The distribution of T. entomospora is restricted to South America.
Small animals tend to grow fast, breed early, and die young. According to MTE, these patterns in life history traits are constrained by metabolism. An organism's metabolic rate determines its rate of food consumption, which in turn determines its rate of growth. This increased growth rate produces trade- offs that accelerate senescence.
For example, metabolic processes produce free radicals as a by-product of energy production. These in turn cause damage at the cellular level, which promotes senescence and ultimately death. Selection favors organisms which best propagate given these constraints. As a result, smaller, shorter lived organisms tend to reproduce earlier in their life histories.
At this new metastatic site, the tumor may undergo other processes to optimize growth. For example, EMT has been associated with PD-L1 expression, particularly in lung cancer. Increased levels of PD-L1 suppresses the immune system which allows the cancer to spread more easily. EMT confers resistance to oncogene-induced premature senescence.
CCN proteins have been shown to play important roles in many cellular processes, including cell adhesion, migration, proliferation, differentiation, survival, apoptosis, and senescence. They are also involved in biological processes including angiogenesis, inflammation, fibrosis, wound healing and tumorigenesis. CCN proteins likely constitute a hub for the coordination of cell signaling and communication.
The process of plant senescence involves the degradation of chlorophyll: for example the enzyme chlorophyllase () hydrolyses the phytyl sidechain to reverse the reaction in which chlorophylls are biosynthesised from chlorophyllide a or b. Since chlorophyllide a can be converted to chlorophyllide b and the latter can be re-esterified to chlorophyll b, these processes allow cycling between chlorophylls a and b. Moreover, chlorophyll b can be directly reduced (via 71-hydroxychlorophyll a) back to chlorophyll a, completing the cycle. In later stages of senescence, chlorophyllides are converted to a group of colourless tetrapyrroles known as nonfluorescent chlorophyll catabolites (NCC's) with the general structure: :Nonfluorescent chlorophyll catabolites These compounds have also been identified in ripening fruits and they give characteristic autumn colours to deciduous plants.
Aubrey de Grey, a leading researcher in the field, defines aging as "a collection of cumulative changes to the molecular and cellular structure of an adult organism, which result in essential metabolic processes, but which also, once they progress far enough, increasingly disrupt metabolism, resulting in pathology and death." The current causes of aging in humans are cell loss (without replacement), DNA damage, oncogenic nuclear mutations and epimutations, cell senescence, mitochondrial mutations, lysosomal aggregates, extracellular aggregates, random extracellular cross-linking, immune system decline, and endocrine changes. Eliminating aging would require finding a solution to each of these causes, a program de Grey calls engineered negligible senescence. There is also a huge body of knowledge indicating that change is characterized by the loss of molecular fidelity.
The antagonistic pleiotropy hypothesis was first proposed by George C. Williams in 1957 as an evolutionary explanation for senescence. Pleiotropy is the phenomenon where one gene controls for more than one phenotypic trait in an organism. Antagonistic pleiotropy is when one gene controls for more than one trait, where at least one of these traits is beneficial to the organism's fitness early on in life and at least one is detrimental to the organism's fitness later on due to a decline in the force of natural selection. The theme of G.C. William's idea about antagonistic pleiotropy was that if a gene caused both increased reproduction in early life and aging in later life, then senescence would be adaptive in evolution.
Antioxidants such as carotenoids, vitamin C, Vitamin E, and enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) can protect against reactive oxygen species that damage DNA, proteins and lipids, and result in cell senescence and death. A cost exists in creating or obtaining these antioxidants. This creates a conflict between the biological fitness benefits of future survival compared with the use of these antioxidants to advantage present reproductive success. In some birds, antioxidants are diverted from maintaining the body to reproduction for this reason with the result that they have accelerated senescence Related to this, birds can show their biological capacity to afford the cost of diverting antioxidants (such as carotenoids) in the form of pigments into plumage as a costly signal.
Histone variants with two exons are upregulated in senescent cells to produce modified nucleosome assembly which contributes to chromatin permissiveness to senescent changes. Although transcription of variant histone proteins may be elevated, canonical histone proteins are not expressed as they are only made during the S phase of the cell cycle and senescent cells are post-mitotic. During senescence, portions of chromosomes can be exported from the nucleus for lysosomal degradation which results in greater organizational disarray and disruption of chromatin interactions. Chromatin remodeler abundance may be implicated in cellular senescence as knockdown or knockout of ATP-dependent remodelers such as NuRD, ACF1, and SWI/SNP can result in DNA damage and senescent phenotypes in yeast, C. elegans, mice, and human cell cultures.
A study of the common supplements and hormone treatments used published in 2006 in the Cleveland Clinic Journal of Medicine showed that none of them are effective with respect to extending life. Another group notices that recent scientific successes in rejuvenation and extending the lifespan of model animals (mice 2.5 times, yeast and nematodes 10 times) and discovery of variety of species (including humans of advanced ages) having negligible senescence give hope to achieve negligible senescence (cancel ageing) for younger humans, reverse ageing, or at least significantly delay it. Moreover, stopping or delaying aging should be a focus of the modern science and medicine since ageing is the major cause of mortality in the world.Brunet Lab: Molecular Mechanisms of Longevity and Age Related Diseases . Stanford.edu.
Auxin is required for fruit growth and development and delays fruit senescence. When seeds are removed from strawberries, fruit growth is stopped; exogenous auxin stimulates the growth in fruits with seeds removed. For fruit with unfertilized seeds, exogenous auxin results in parthenocarpy ("virgin-fruit" growth). Fruits form abnormal morphologies when auxin transport is disturbed.
Auxin plays also a minor role in the initiation of flowering and development of reproductive organs. In low concentrations, it can delay the senescence of flowers. A number of plant mutants have been described that affect flowering and have deficiencies in either auxin synthesis or transport. In maize, one example is bif2 barren inflorescence2.
Phalaenopsis are unique in that in some species, the flowers turn into green leaves after pollination. As in many other plants, the petals of the orchid flowers serve to attract pollinating insects and protect essential organs. Following pollination, petals usually will undergo senescence (i.e. wilt and disintegrate) because it is metabolically expensive to maintain them.
Senescence is the act of ageing in individuals; it's the failure over time of the individual's life processes by natural causes. Williams's theory has been the motivation for many of the experimental studies on the reasons for aging in the last 25 years.Fox, C.W. and J.B. Wolf. 2006. Evolutionary Genetics: Concepts and Case Studies.
Timing of initial arrival at the breeding site predicts age at first reproduction in a long-lived migratory bird. PNAS 105:12349-12352. They increase their breeding success with age and experience, until around the age of 15, when senescence seems to set in.Rebke, M., T. Coulson, P. H. Becker, and J. W. Vaupel. 2010.
In contrast to cellular senescence, quiescence is not a reactive event but part of the core programming of several different cell types. Finally, differentiated cells are stem cells that have progressed through a differentiation program to reach a mature – terminally differentiated – state. Differentiated cells continue to stay in G0 and perform their main functions indefinitely.
Even as Ding forgets his family members, he remembers his relationship with Cherry, who cares for him well into his senescence. In a scene after the credits, the two countryside criminals accidentally encounter a group of drilling PLA military police, who turn and give chase. After a short chase the remaining criminals are captured.
Because there are so many different hosts for this pathogen, the symptoms are very variable. Common symptoms include abnormal leaf color, abnormal leaf form, wilting leaves, galls, swollen roots, reduced root system, dwarfing and senescence (Cabi 2018). This pathogen does the most damage when present in light soils with hot weather conditions (Alford 2012).
Effros, R.B., Allsopp, R., Chiu, C.P., Hausner, M.A., Hirji, K., Wang, L., Harley, C.B., Villeponteau, B., West, M.D., and Giorgi, J.V. (1996). Shortened telomeres in the expanded CD28-CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis. Aids 10, F17-22.von Zglinicki, T., Saretzki, G., Docke, W., and Lotze, C. (1995).
Amyloid beta immunostaining showing senile plaques. Senile plaques (also known as neuritic plaques, or amyloid plaques) are extracellular deposits of amyloid beta in the grey matter of the brain. Degenerative neural structures and an abundance of microglia and astrocytes can be associated with senile plaque deposits. These deposits can also be a byproduct of senescence (aging).
People with diabetes, who have elevated blood sugar, develop senescence-associated disorders much earlier than the general population, but can delay such disorders by rigorous control of their blood sugar levels. There is evidence that sugar damage is linked to oxidant damage in a process termed glycoxidation. Free radicals can damage proteins, lipids or DNA. Glycation mainly damages proteins.
NWSV produces greenish-purple streaking on the leaves and stem turning white to yellow, and premature senescence reducing bulb size and yield. These viruses are primarily diseases of commercial nurseries. The growth inhibition caused by viral infection can cause substantial economic damage. ; Bacteria : Bacterial disease is uncommon in Narcissus but includes Pseudomonas (bacterial streak) and Pectobacterium carotovorum sp.
The opossum lifespan is unusually short for a mammal of its size, usually only one to two years in the wild and as long as four or more years in captivity. Senescence is rapid.Opossum Facts. opossum.org. The species are moderately sexually dimorphic with males usually being slightly larger, much heavier, and having larger canines than females.
Plasmablastic lymphoma (PBL) is an uncommon lymphoma that occurs mostly in immune-deficient individuals, primarily those with HIV/AIDS. Indeed, it is an AIDS-defining clinical condition. The disease can also occur in those who have had an organ transplantation or chemotherapy treatment or are presumed to have age-related immune senescence. Chronic autoimmune or inflammatory diseases (e.g.
15, 2007 The rapid senescence of opossums is thought to reflect the fact that they have few defenses against predators; given that they would have little prospect of living very long regardless, they are not under selective pressure to develop biochemical mechanisms to enable a long lifespan.Karen Wright Staying Alive. Discover Magazine. November 6, 2003 Accessed Oct 15, 2007.
Menopause has been observed in several species of nonhuman primates, including rhesus monkeys and chimpanzees.Bowden, D. M. and Williams, D. D. (1985). Aging. Adv.Vet.Sci.Comp.Med. 28: 306–41 Menopause also has been reported in a variety of other vertebrate species including elephants, short-finned pilot whales,Marsh, H and Kasuya, T. (1986). Evidence for Reproductive Senescence in Female Cetaceans.
Virta-Pearlman V, Morris DK, Lundblad V. (1996) "Est1 has the properties of a single-stranded telomere end-binding protein." Genes Dev. 10(24):3094-104. Lendvay TS, Morris DK, Sah J, Balasubramanian B, Lundblad V. (1996) "Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes." Genetics 144(4):1399-412.
Duvelisib is a Phosphoinositide 3-kinase inhibitor, specifically of the delta and gamma isoforms of PI3K. This class of compounds works by preventing PI3K from playing its role in transducing signals from outside of cells into various intracellular pathways involved in cell cycle regulation, apoptosis, DNA repair, senescence, angiogenesis and cell metabolism, including the PI3K/AKT/mTOR pathway.
Soil organic carbon is divided between living soil biota and dead biotic material derived from biomass. Together these comprise the soil food web, with the living component sustained by the biotic material component. Soil biota includes earthworms, nematodes, protozoa, fungi, bacteria and different arthropods. Detritus resulting from plant senescence is the major source of soil organic carbon.
There is more conservation across species in TERF2 possibly due to higher risk of senescence when mutated. TERF2 binds directly to the DNA sequence, forming a T-loop structure. Therefore, TERF2 plays a role in inducing loop formation by folding the 3’ TTAGGG sequence back into the duplex sequence. When removed, degradation of telomeric 3’ overhangs can be observed.
In the leaves, the MMP gene was expressed in the phloem, developing xylem elements, neighboring mesophyll cell layers, and epidermal cells. The flowers were noted as having the gene in pistils, ovules, and receptacles. It was concluded that the At2-MMP has a physiological role in mature aging tissue and the possibility of being involved in plant senescence.
ID4 is a protein coding gene. In humans, it encodes for the protein known as DNA-binding protein inhibitor ID-4. This protein is known to be involved in the regulation of many cellular processes during both prenatal development and tumorigenesis. This is inclusive of embryonic cellular growth, senescence, cellular differentiation, apoptosis, and as an oncogene in angiogenesis.
Camelthorn tree within Sossusvlei Senescence refers to a scenario when a living being is able to survive all calamities, but eventually dies due to causes relating to old age. Animal and plant cells normally reproduce and function during the whole period of natural existence, but the aging process derives from deterioration of cellular activity and ruination of regular functioning. Aptitude of cells for gradual deterioration and mortality means that cells are naturally sentenced to stable and long-term loss of living capacities, even despite continuing metabolic reactions and viability. In the United Kingdom, for example, nine out of ten of all the deaths that occur on a daily basis relates to senescence, while around the world it accounts for two- thirds of 150,000 deaths that take place daily (Hayflick & Moody, 2003).
Multiple mechanisms of action have been studied in both pre-clinical and clinical settings. Instead of directly killing the tumor cells, the drugs in metronomic therapy suppress tumor growth mainly by inhibiting tumor angiogenesis and modulating the immune response against tumors. There is also emerging evidence that metronomic therapy may also act on tumor cells by inducing tumor dormancy and senescence.
The Hayflick limit deliberates that the average cell will divide around 50 times before reaching a stage known as senescence. As the cell divides, the telomeres on the end of a linear chromosome get shorter. The telomeres will eventually no longer be present on the chromosome. This end stage is the concept that links the deterioration of telomeres to aging.
Cardiac senescence, or cellular deterioration that occurs as part of normal aging, closely resembles the manifestations of HFpEF. Specifically, loss of cardiac reserve, diminished vascular compliance, and diastolic dysfunction are characteristic of both processes. It has been suggestedLam, C. S., Donal, E., Kraigher‐Krainer, E., & Vasan, R. S. (2011). Epidemiology and clinical course of heart failure with preserved ejection fraction.
Because the plant is harvested in an earlier stage than flowering, normally the flowers are not visible on the field. It develops similar to other head-forming leaf vegetables, for example cabbage lettuce. The chronological stages on the BBCH-scale are germination, leaf formation, vegetative growth (head-forming), appearance of the sprout that bears the flowers, flowering, fruit development, seed ripening and senescence.
Some E. coli strains contain a polyketide synthase genomic island (pks), which encodes a multi- enzymatic machinery that produces colibactin, a substance that damages DNA. About 20% of humans are colonized with E. coli that harbor the pks island. Colibactin can cause cellular senescence or cancer by damaging DNA. However, the mucosal barrier prevents E. coli from reaching the surface of enterocytes.
Flower longevity varies by species and conditions, ranging from 5–20 days. After flowering leaf and root senescence sets in, and the plant appears to be 'dormant' till the next spring, conserving moisture. However the dormant period is also one of considerable activity within the bulb primordia. It is also a period during which the plant bulb may be susceptible to predators .
This is evident as ethylene production and emission are maximized in developmental phases post-pollination, until corolla wilting. Ethylene-directed senescence of corolla tissue can be observed as color change in the corolla or the wilting/ death of corolla tissue. At the chemical level, ethylene mediates the reduction in the amount of fragrance volatiles produced. Fragrance volatiles act mostly by attracting pollinators.
In 1996, NASA sponsored Stoner’s research for a natural liquid biocontrol, known then as ODC (organic disease control), that activates plants to grow without the need for pesticides as a means to control pathogens in a closed-loop culture system. ODC is derived from natural aquatic materials.Linden, J.C. and Stoner, R.J. (2005). Proprietary Elicitor Affects Seed Germination and Delays Fruit Senescence.
Histone lysine methylation marks also defined bivalent chromatin in embryonic stem cells and are instructive chromatin modifications that are used for epigenomic profiling in normal vs. diseased cells. They were also a crucial prerequisite for the later discoveries of histone demethylases (KDM). With all of these mechanistic insights, novel approaches in cancer biology, complex human disorders, cell senescence and reprogramming have become possible.
A single leaf of marram grass, showing the rolled leaf which reduces water loss Ammophila arenaria is a perennial plant, which means it can live for many years. It mainly grows in spring when leaf production exceeds lead senescence. However, the conditions in autumn cause the plant to nearly stop growth while its leaves become aged.Encyclopedia of Life, 2015, Ammophila arenaria.
Cellular senescence does not occur in most cancer cells due to expression of an enzyme called telomerase. This enzyme extends telomeres, preventing the telomeres of cancer cells from shortening and giving them infinite replicative potential. A proposed treatment for cancer is the usage of telomerase inhibitors that would prevent the restoration of the telomere, allowing the cell to die like other body cells.
Being very shade intolerant, most shaded stems die. They are pioneer species on disturbed sites, persisting in successional communities until senescence. Rapid height growth of suckers allows it to outcompete other sprouting species such as red oak (Quercus rubra) and red maple (Acer rubrum) on many sites. In the absence of disturbance, it is soon replaced by conifers and hardwoods.
Females begin to exhibit signs of senescence around July. The indicative behavior includes resting in flowers, remaining in the nest, or even just falling to the ground from flight. Older individuals also crawl, avoid taking flight, and do not struggle when handled by humans. The old bees die by early August, the same time that juveniles emerge from brood cells.
Longevity senescence and the genome. University of Chicago Press. London. Notably, the survival time past menopause is roughly the same as the maturation time for a human child. That a mother's presence could aid in the survival of a developing child, while an unidentified father's absence might not have affected survival, could explain the paternal fertility near the end of the father's lifespan.
Carrel was also interested in the phenomenon of senescence, or aging. He claimed that all cells continued to grow indefinitely, and this became a dominant view in the early 20th century. page 24. Carrel started an experiment on 17 January 1912, where he placed tissue cultured from an embryonic chicken heart in a stoppered Pyrex flask of his own design.
GHK-Cu stimulates proliferation of keratinocytes and increased expression of integrins and p63 protein in the epidermal stem cells. Since p63 is considered to be an important marker of stem cell and anti-senescence protein, the authors concluded that GHK-copper is able to recover epidermal stem cells and increase their ability to repair tissue. Similar activity was observed for copper-free GHK.
In 1905 he was named president of the Société zoologique de France. In 1920 he became a member of the Académie des Sciences. Joubin's squid (Joubiniteuthis portieri) is named for him, fauna - Joubin's Squid (Joubiniteuthis portieri) as is Scolymastra joubini, a hexactinellid sponge whose lifespan is purportedly 10,000 years. Genomics senescence, Scolymastra joubini Joubin's laboratory at the Institut Océanographique (1911).
The cell cycle hypothesis of AD also attempts to explain for the characteristic senile plaques and the neurofibrillary tangles of AD pathology. The intracellular accumulation of highly phosphorylated tau is linked to the cell cycle and cell cycle dependent kinases (McShea et al., 2007). Other aberrations in cell cycle dynamics influence cell senescence, oxidative stress, and misregulated apoptosis (Franco et al.
MEFs show a spindle shape when cultured in vitro, a typical feature of fibroblasts. The MEF is a limited cell line. After several transmission, MEFs will senescence and finally die off. Nevertheless, researchers can use several strategies, like virus infection or repeated transmission to immortalize MEF cells, which can let MEFs grown indefinitely in spite of some changes in characters.
Females who were exposed to two males continuously without a refractory period in between lay fewer eggs, but still lay more eggs than females with only one male. Therefore, there appears to be a reproductive benefit for females with polyandry. Reproductive senescence does appear to be present in this species, as male and female age correlates negatively with the rate of fertilization.
Over-expression of cyclin E correlates with tumorigenesis. It is involved in various types of cancers, including breast, colon, bladder, skin and lung cancer. DNA copy-number amplification of cyclin E1 is involved in brain cancer. Besides that, dysregulated cyclin E activity causes cell lineage-specific abnormalities, such as impaired maturation due to increased cell proliferation and apoptosis or senescence.
Telomere shortening in humans can induce replicative senescence, which blocks cell division. This mechanism appears to prevent genomic instability and development of cancer in human aged cells by limiting the number of cell divisions. However, shortened telomeres impair immune function that might also increase cancer susceptibility. If telomeres become too short, they have the potential to unfold from their presumed closed structure.
The model suggests that heterochromatin provides a fundamental epigenetic mechanism that underlies most of the changes in gene expression in senescence. Recent research in Drosophila has supported this heterochromatin loss modelLarson, K., Yan, S.J., Tsurumi, A., Liu, J., Zhou, J., Gaur, K., Guo, D., Eickbush, T.H., and Li, W.X. (2012). Heterochromatin formation promotes longevity and represses ribosomal RNA synthesis. PLoS Genetics 8, e1002473.
Twist1 and Twist2, as well as ZEB1 protects human cells and mouse embryonic fibroblasts from senescence. Similarly, TGF-β can promote tumor invasion and evasion of immune surveillance at advanced stages. When TGF-β acts on activated Ras-expressing mammary epithelial cells, EMT is favored and apoptosis is inhibited. This effect can be reversed by inducers of epithelial differentiation, such as GATA-3.
Golldack, D., Popova, O., & Dietz, K. (2002). Mutation of the Matrix Metalloproteinase At2-MMP Inhibits Growth and Causes Late Flowering and Early Senescence in Arabidopsis. The Journal of Biological Chemistry, 277 (7) 5541-5547. The fungus Chondrostereum purpureum, the causal agent of silver leaf, was grown in liquid culture and agar, which caused it to secrete extracellular proteinases into the medium.
The adult plants are killed by wildfires, but the seeds can survive such an event. The flowers are pollinated by birds. The fruits are numerous, studding the base of the dried, old flower head, which itself remains attached to the plant after senescence. The seeds are retained in the fruits for a few years, until they are eventually dispersed by the wind.
Other pests include caterpillars, thrips, slugs and snails. Another problem is mildew; this is a white powdery coating that covers the leaves and slows down growth. The sweet pea is also susceptible to ethylene in quantities produced by senescing plants. Because of this, growers are encouraged to plant sweet peas away from fruit trees among other plants prone to early dieback or senescence.
As normal human fibroblasts replicate and progress towards replicative senescence the capability to undergo homologous recombinational repair (HRR) declines. However, over-expression of SIRT6 in “middle-aged” and pre-senescent cells strongly stimulates HRR. This effect depends on the mono-ADP ribosylation activity of poly(ADP-ribose) polymerase (PARP1). SIRT6 also rescues the decline in base excision repair of aged human fibroblasts in a PARP1 dependent manner.
The most effective treatment found for closed calyx fruit was to submerge the fruit in the calcium chloride solution and to apply a vacuum and immediately rinsing in water.Scott, K. J., and Wills, R. B. H. (1977). Vacuum infiltration of calcium chloride: A method for reducing bitter pit and senescence of apples during storage at ambient temperatures. HortScience. 12 : 71-72Scott, K.J., and Wills, W.B.H. (1979).
While this may not cause pain in some people, in others it may cause chronic pain. Other spinal disorders can affect the morphology of intervertebral discs. For example, patients with scoliosis commonly have calcium deposits (ectopic calcification) in the cartilage endplate and sometimes in the disc itself. Herniated discs are also found to have a higher degree of cellular senescence than non-herniated discs.
Some species have sheaths that persist over years and typically have deciduous blades, and some species have sheaths that quickly shred into fibers and decay in senescence and typically have blades that are not deciduous. Species lack auricles. The membranous ligules measure and are typically longest at the margins. The ligules are typically truncate and ciliate, though they can occasionally be acute or erose.
Methyl jasmonate (abbreviated MeJA) is a volatile organic compound used in plant defense and many diverse developmental pathways such as seed germination, root growth, flowering, fruit ripening, and senescence. Methyl jasmonate is derived from jasmonic acid and the reaction is catalyzed by S-adenosyl-L-methionine:jasmonic acid carboxyl methyltransferase.Christie, William W. Plant oxylipins: Chemistry and biology, 22 May 2014. Archived from the original on 2015-06-30.
Another example related to aging is the Telomere theory. Telomere theory proposes that telomeres shorten with repeated cell division which attribute to cell senescence and tissue damage. The end replication problem explains the mechanism behind the inability of DNA polymerase to commence the RNA primer to perform its function in completing the lagging strand due to the shortening of DNA. Telomere shortening is common in somatic cells.
Similar symptoms appear on leaves in the field, causing premature senescence and favouring bacterial spoilage in the cold store after harvest. Affected Brussels sprouts show black spotting, which reduces their market quality. The heads of flowerhead brassicas can be severely affected, and become unmarketable. Control by fungicide treatment is essential at the seed-bed stage, with reduction of humidity and leaf wetness as fas as possible.
Hayflick demonstrated that a normal human fetal cell population will divide between 40 and 60 times in cell culture before entering a senescence phase. This finding refuted the contention by French Nobel laureate Alexis Carrel that normal cells are immortal. Each time a cell undergoes mitosis, the telomeres on the ends of each chromosome shorten slightly. Cell division will cease once telomeres shorten to a critical length.
Hayflick describes three phases in the life of normal cultured cells. At the start of his experiment he named the primary culture "phase one". Phase two is defined as the period when cells are proliferating; Hayflick called this the time of "luxuriant growth". After months of doubling the cells eventually reach phase three, a phenomenon he named "senescence", where cell replication rate slows before halting altogether.
The lifespan of cuttlefish is only around one to two years, depending on the species. They hatch from eggs fully developed, around a quarter of an inch long, reaching one inch around the first two months. Before death cuttlefish go through senescence when the cephalopod essentially deteriorates, or rots in place. Their eyesight begins to fail which affects their ability to see, move, and hunt efficiently.
Encorafenib acts as an ATP-competitive RAF kinase inhibitor, decreasing ERK phosphorylation and down-regulation of CyclinD1. This arrests the cell cycle in G1 phase, inducing senescence without apoptosis. Therefore, it is only effective in melanomas with a BRAF mutation, which make up 50% of all melanomas. The plasma elimination half-life of encorafenib is approximately 6 hours, occurring mainly through metabolism via cytochrome P450 enzymes.
It grows in sandy or granite soils, at altitudes of 400 to 1,200 metres. It is usually found in a fynbos habitat, but sometimes also grows on shale, or in renosterveld or scrubland. The adult plants are killed by the periodic wildfires of its habitat, but its seeds survive these events. The fruits are woody and persistent, which means they are retained on the plant after senescence.
The natural aging of cells, called their cellular senescence, is one of the main contributors to aging on an organismal level. There are a few different ideas to the cause behind why aging happens on a cellular level. Telomere length has been shown to positively correlate to longevity. Increased circulation of progenitor cells in the body has also positively correlated to increased longevity and regenerative processes.
Mouse mutants with homozygous defects in Ku80 experience an early onset of senescence. Ku80(-/-) mice exhibit aging-related pathology (osteopenia, atrophic skin, hepatocellular degeneration, hepatocellular inclusions, hepatic hyperplastic foci and age-specific mortality). Furthermore, Ku80(-/-) mice exhibit severely reduced lifespan and size. Loss of only a single Ku80 allele in Ku(-/+) heterozygous mice causes accelerated aging in skeletal muscle, although post natal growth is normal.
An analysis of the level of Ku80 protein in human, cow, and mouse indicated that Ku80 levels vary dramatically between species, and that these levels are strongly correlated with species longevity. These results suggest that the NHEJ pathway of DNA repair mediated by Ku80 plays a significant role in repairing double-strand breaks that would otherwise cause early senescence (see DNA damage theory of aging).
In cycling cells, there is a resassortment of Cip/Kip proteins between CDK4/5 and CDK2 as cells progress through G1. Their function, inhibiting CDK4/6, is to block progression of the cell cycle beyond the G1 restriction point. In addition, INK4 proteins play roles in cellular senescence, apoptosis and DNA repair. INK4 proteins are tumor suppressors and loss-of-function mutations lead to carcinogenesis.
Previously, medical agents could only be effective by directing and inducing the patients own cells. However, in many diseases and disorders, cell are compromised by e.g. senescence, limited blood supply (ischemia), inflammation, or simply a reduction in the number of cells. Cell therapy offers a new strategy that supports the introduction of new and active cells to restore previously compromised or deteriorated tissue- and organ structures.
In addition to his other work and publications, Austriaco is the founder and chief researcher at the Austriaco Lab. The laboratory is located at Providence College and is composed of both students and faculty. The laboratory researches programmed cell death (PCD) such as cell senescence and apoptosis. Research is done on yeast cells, which are genetically manipulated and observed in order to better understand PCD.
The cell may detect this uncapping as DNA damage and then either stop growing, enter cellular old age (senescence), or begin programmed cell self-destruction (apoptosis) depending on the cell's genetic background (p53 status). Uncapped telomeres also result in chromosomal fusions. Since this damage cannot be repaired in normal somatic cells, the cell may even go into apoptosis. Many aging-related diseases are linked to shortened telomeres.
Biochemistry 55: 5952-5961 # Müller. T., Rasool, I., et al (2015) Congenital secretory diarrhoea caused by activating germline mutations in GUCY2C. Gut doi: 10.1136/gutjnl-2015-309441 # Basu et al (2014) Intestinal cell proliferation and senescence is regulated by receptor guanylyl cyclase C and p21 J. Biol. Chem. 289: 581-93 # Fiskerstand, T., Arshad et al (2012) Familial Diarrhea Syndrome caused by an activating GUCY2C mutation.
259, 1769–1771 . and cell aging (senescence). Numerous research works have focused interest on defining the direct protein targets of action of ceramide. These include enzymes called ceramide-activated Ser-Thr phosphatases (CAPPs), such as protein phosphatase 1 and 2A (PP1 and PP2A), which were found to interact with ceramide in studies done in a controlled environment outside of a living organism (in vitro).
Its regression has been linked to the reduction in immunosurveillance and the rise of infectious disease and cancer incidence in the elderly (in some cases risk is inversely proportional to thymus size). Though thymic involution has been linked to immunosenescence, it is not induced by senescence as the organ starts involuting from a young age: in humans, as early as the first year after birth.
It is implied that he fears such a meeting would expose the implausible age gap in their relationship. Ultimately, Kepesh limits their relationship to the physical instead of embarking upon any deeper arrangement. In the end, Kepesh is destroyed by his indecisiveness, the fear of senescence, his lust and jealousy. Consuela never subsequently finds a lover who can show the same level of devotion to her body as Kepesh had.
Immortalised cell lines are an important research tool offering a stable medium for experiments. These are derived either from tumors, which have developed resistance to senescence, or, in a few cases, from stem cells taken from aborted fetuses. Fetal cell lines have been used in the manufacture of viruses since 1930s. One of the first medical applications of fetal tissues was their use in the production of the first polio vaccines.
The cytokinin zeatin is named after the genus of corn, Zea. Cytokinins (CK) are a class of plant growth substances (phytohormones) that promote cell division, or cytokinesis, in plant roots and shoots. They are involved primarily in cell growth and differentiation, but also affect apical dominance, axillary bud growth, and leaf senescence. Folke Skoog discovered their effects using coconut milk in the 1940s at the University of Wisconsin–Madison.
The products are mainly associated with inflammation, proliferation, and changes in the extracellular matrix. A Senescence Associated Secretory Phenotype (SASP) consisting of inflammatory cytokines, growth factors, and proteases is another characteristic feature of senescent cells. There are many SASP effector mechanisms that utilize autocrine or paracrine signalling. SASP induces an unfolded protein response in the endoplasmic reticulum because of an accumulation of unfolded proteins, resulting in proteotoxic impairment of cell function.
Growth factors, GM-CSF and VEGF also serve as SASP molecules. From the cellular perspective, cooperation of transcriptional factors NF-κB and C/EBPβ increase the level of SASP expression. Regulation of the SASP is managed through a transcription level autocrine feedback loop, but most importantly by a continuous DDR. Proteins p53, p21, p16ink4a, and Bmi-1 have been termed as major senescence signalling factors, allowing them to serve as markers.
There are several reported signaling pathways that lead to cellular senescence including the p53 and p16Ink4a pathways. Both of these pathways are activated in response to cellular stressors and lead to cell cycle inhibition. p53 activates p21 which deactivates cyclin-dependent kinase 2(Cdk 2). Without Cdk 2, retinoblastoma protein (pRB) remains in its active, hypophosphorylated form and binds to the transcription factor E2F1, an important cell cycle regulator.
As a result, this species has the highest rate of seed viability recorded for a Banksia species: in one study, 74% of all seed produced in the previous 12 years was viable. This was largely accounted for by seed under 9 years old, about 90% of which is viable. After the ninth year, viability is lost rapidly as the follicles decay and senescence sets in. Seed production itself starts very slowly.
Nucleolar protein 12 is a protein that in humans is encoded by the NOL12 gene. Human NOL12 has been shown to localize in the nucleolus and regulate nucleolar structure and homeostasis by maintaining the levels of multi-functional fibrillarin and nucleolin proteins. Its deficiency leads to p53 activation resulting in G2 arrest of cell. Nol12 or hNol12 drives p53 induced cell senescence suggesting its important role in aging.
Duration of crop growth cycles are above all, related to temperature. An increase in temperature will speed up development. In the case of an annual crop, the duration between sowing and harvesting will shorten (for example, the duration in order to harvest corn could shorten between one and four weeks). The shortening of such a cycle could have an adverse effect on productivity because senescence would occur sooner.
A condition possibly resulting from a reduction in neuroangiogenic factors is Alzheimer’s disease. Without continued neuroangiogenesis during aging, areas of the brain may no longer have the full complement of functional capillaries and hence, by inference, cerebral blood flow and cognitive ability decline. This condition of reduced neuroangiogenesis and lower capillary density during senescence, possibly involving impaired regulation of angiogenic factors by hypoxia, could be a vascular basis for Alzheimer's disease.
This includes fur loss, parasite infestations, and weight loss. As the mating period went on, males became increasingly anemic, but the anemia was not due to ulceration or gastrointestinal bleeding. Lack of elevated cortisol levels during mating periods in D. hallucatus means that there is no current universal explanation for the mechanism behind increased male mortality in Dasyuridae. Post-reproductive senescence has also been proposed as an explanation.
Qualitative differences have been found between senescent cells and normal cells, including differential expression of cytokines and other factors associated with inflammation. It is believed that this may contribute, in part, to cellular aging. In sum, although mechanisms encoded by gatekeeper and caretaker genes to protect individuals from cancer early in life, namely induction of apoptosis or senescence, later in life these functions may promote the aging phenotype.
Monarch butterflies are thought to respond to different cues that promote the fall season, southern migration. These include the angle of light coming from the sun, the senescence of larval host plants, the decreasing day period and temperature drop. The migration begins at the northernmost summer range approximately in August. Migrating monarchs are thought to rely heavily on the nectar of fall flower composites that lie along the migration path.
Monolopia major is endemic to Central California with known extant populations in the Inner North Coast Ranges and Inner South Coast Ranges. The species is frequently confused with Monolopia lanceolata, with the two being very similar in appearance. The two can be distinguished by M. major having fused phyllaries - fused into a cup; most obvious at after senescence and fruits have dispersed. In comparison, M. lanceolata has free phyllaries.
With age, tissue homeostasis declines partly because stem/progenitor cells fail to self-renew or differentiate. DNA damage caused by exposure of stem/progenitor cells to reactive oxygen species (ROS) may play a key role in epidermal stem cell aging. Mitochondrial superoxide dismutase (SOD2) ordinarily protects against ROS. Loss of SOD2 in mouse epidermal cells was observed to cause cellular senescence that irreversibly arrested proliferation in a fraction of keratinocytes.
Balanced inflammation is an important factor in maintaining fetal membranes by regulating the remodeling. However, if the inflammatory response increases above this level it can have dangerous and potentially fatal effects for the mother and child. These elevated levels of inflammatory molecules in the fetal membrane is called ‘sterile inflammation’. Sterile inflammation can be caused by both microbial infection and non-infectious factors, such as senescence of fetal membranes.
Poor ovarian reserve is a condition of low fertility characterized by 1): low numbers of remaining oocytes in the ovaries or 2) possibly impaired preantral oocyte development or recruitment. Recent research suggests that premature ovarian aging and premature ovarian failure (aka primary ovarian insufficiency) may represent a continuum of premature ovarian senescence. It is usually accompanied by high FSH (follicle stimulating hormone) levels. Quality of the eggs may also be impaired.
Both pathways can result in transient or permanent cell-cycle arrests, but the exact mechanisms in which these processes differ are still unknown. Much less is known about the relationship between cellular senescence and aging. However, it has been shown that the number of senescent cells increases in many tissues with age, and senescent cells are found at the site of several age-related pathologies, such as osteoarthritis and osteoporosis.
An increase in photosynthetic rate in undamaged tissues is commonly cited as a mechanism for plants to achieve tolerance (Trumble et al. 1993; Strauss and Agrawal 1999). This is possible since leaves often function at below their maximum capacity (Trumble et al. 1993). Several different pathways may lead to increases in photosynthesis, including higher levels of the Rubisco enzyme and delays in leaf senescence (Stowe et al. 2000).
Annual survival probability for birds aged 6–15 is 0.895, and average lifespan is about 20 years. Breeding success increases with age up to age 9-10 to 0.7 fledglings per pair, then declines in the oldest age birds, perhaps indicating reproductive senescence. High densities mean that birds are close contact with neighbouring breeders.Birkhead (1978) Common murres perform appeasement displays more often at high densities and more often than razorbills.
Inquiry into the evolution of aging aims to explain why so many living things and the vast majority of animals weaken and die with age (exceptions include Hydra and the already cited jellyfish Turritopsis dohrnii, which research shows to be biologically immortal). The evolutionary origin of senescence remains one of the fundamental puzzles of biology. Gerontology specializes in the science of human aging processes. Organisms showing only asexual reproduction (e.g.
However, CYR61 can also induce apoptosis and cellular senescence, two well- established mechanisms of tumor suppression Thus, whereas CYR61 can promote the proliferation of prostate cancer cells, it can also exacerbate apoptosis of these cells in the presence of the immune surveillance molecule TRAIL. CYR61 has an inhibitory effect on some cancers, and suppresses tumor growth of non-small-cell lung cancer (NSCLC) cells, endometrial adenocarcinoma cells, and in melanoma cells.
Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells resulting in progressive shortening of telomeres. Deregulation of telomerase expression in somatic cells may be involved in oncogenesis. Studies in mice suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. Homologs of TERC can also be found in the Gallid herpes viruses.
Likewise, subordinates decrease foraging rate following worker emergence. However, unlike other polistine wasps, more severe consequences occur for P. annularis after worker emergence, despite this change in behavior. The intricacies of this conundrum remain unsolved though are suspected to deal with senescence as decreased foraging also accompanies decreased aggression. Foundress eviction, as studied across polistine wasps, is independent of the rate of usurpation, which is 9% in P. annularis.
This species is capable of making fine-quality pearls, and was historically exploited in the search for pearls from wild sources. In recent times, the Russian malacologist Valeriy Zyuganov received worldwide reputation after he discovered that the pearl mussel exhibited negligible senescence and he determined that it had a maximum lifespan of 210–250 years. The data of V.V. Zyuganov have been confirmed by Finnish malacologists and gained general acceptance.
Oecologia 82(2):227-237. The larvae typically settle on their preferred substrates in May, and then the colony undergoes growth, stasis and reproduction, shrinkage, and senescence around September, except in regions where temperature allows them to persist further into the winter. The presence of conspecifics may cause a colony to stop growing and begin stasis and reproduction early. The presence of predators also reduces growth of a colony.
Regulation of p16 is complex and involves the interaction of several transcription factors, as well as several proteins involved in epigenetic modification through methylation and repression of the promoter region. PRC1 and PRC2 are two protein complexes that modify the expression of p16 through the interaction of various transcription factors that execute methylation patterns that can repress transcription of p16. These pathways are activated in the cellular response to reduce senescence.
Potato root nematodes or potato cyst nematodes (PCN) are 1-mm long roundworms belonging to the genus Globodera, which comprises around 12 species. They live on the roots of plants of the family Solanaceae, such as potatoes and tomatoes. PCN cause growth retardation and, at very high population densities, damage to the roots and early senescence of plants. The nematode is not indigenous to Europe but originates from the Andes.
Stem cells decrease in number and tend to lose the ability to differentiate into progenies or lymphoid lineages and myeloid lineages. Maintaining the dynamic balance of stem cell pools requires several conditions. Balancing proliferation and quiescence along with homing (See niche) and self-renewal of hematopoietic stem cells are favoring elements of stem cell pool maintenance while differentiation, mobilization and senescence are detrimental elements. These detrimental effects will eventually cause apoptosis.
However, this compromise is thought to damage somatic repair systems, which can lead to progressive cellular damage and senescence. Repair costs can be categorized into three groups: (1) the costs of increased durability of nonrenewable parts; (2) the costs of maintenance involving cell renewal, and (3) the costs of intracellular maintenance. In a nutshell, aging and decline is essentially a trade-off for increased reproductive robustness in youth.
There are two views of an organisation's life cycle. The first, linear view is that (like organic life) organisations progress through stages from birth, infancy, adolescence, maturity, senescence and death. The second view is that within this continuum organisations can start at different points and skip (or repeat) stages in cycles. For instance, with appropriate support and backing an organisation can begin its life in a fully formed, "mature" state.
The level of production of the different CPEB proteins determines whether the expression of Myc leads to tumor formation. The tumor suppressor gene TP53 has also been shown to be regulated by a CPE. Cell lines that do not produce CPEB show lower levels of the protein p53 and become immortal instead of showing senescence. The eCPE and the C-CPE are two other cytoplasmic polyadenylation elements that are found within embryos.
"The force of natural selection weakens with increasing age—even in a theoretically immortal population, provided only that it is exposed to real hazards of mortality. If a genetic disaster... happens late enough in individual life, its consequences may be completely unimportant". The 'real hazards of mortality' such as predation, disease, and accidents, are known 'extrinsic mortality', and mean that even a population with negligible senescence will have fewer individuals alive in older age groups.
Senescence-associated secretory phenotype (SASP) is a phenotype associated with senescent cells wherein those cells secrete high levels of inflammatory cytokines, immune modulators, growth factors, and proteases. SASP may also consist of exosomes and ectosomes containing enzymes, microRNA, DNA fragments, and other bioactive factors. SASP is heterogenous, with the exact composition dependent upon the senescent-cell inducer and the cell type. Initially, SASP is immunosuppressive and profibrotic, but progresses to become proinflammatory and fibrolytic.
SASP expression is induced by a number of transcription factors, including C/EBPβ, of which the most important is NF-κB. NF-κB is expressed as a result of inhibition of autophagy-mediated degradation of the transcription factor GATA4. GATA4 is activated by the DNA damage response factors, which induce cellular senescence. Aberrant oncogenes, DNA damage, and oxidative stress induce mitogen-activated protein kinases, which are the upstream regulators of NF-κB.
More and more countries are using health expectancy indicators to monitor the health of their population. The long-standing quest for longer life led in the 2010s to a more promising focus on increasing HALE, also known as a person's "healthspan". Besides the benefits of keeping people healthier longer, a goal is to reduce health-care expenses on the many diseases associated with cellular senescence. Approaches being explored include fasting, exercise, and senolytic drugs.
This induces replicative senescence. Some cells do not age and are described as being "biologically immortal". Theoretically, it is possible upon the discovery of the exact mechanism of biological immortality to genetically engineer cells with the same capability. The length of the telomere strand has senescent effects; telomere shortening activates extensive alterations in alternative RNA splicing that produce senescent toxins such as progerin, which degrades tissue and makes it more prone to failure.
This correlates with the nutritional quality of the tree's sap. This is high in the early season spurt of growth, falls in the middle of the summer and rises again in late summer with senescence setting in. At this time the tree is transferring organic products out of the leaves (which will soon be shed) to the trunk and roots for storage. This richer saps seem to stimulate the aphids to resume reproductive activity.
Pollination occurs through the visits of either rats, mice, birds or insects. The seeds are stored in the fruit after becoming ripe, and the fruit are themselves stored in the old, dried, fire-resistant inflorescences, which are persistently retained on the plant after senescence. The inflorescences open one to two years after flowering after fires have passed through the land. When released from their capsules, the seeds are eventually dispersed by means of the wind.
This gene encodes a purine- converting ectoenzyme which belongs to the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) family. The encoded protein hydrolyzes extracellular nucleoside triphosphates (UTP, GTP, and CTP) to nucleoside monophosphates as part of a purinergic signaling pathway. It contains two transmembrane domains at the N- and C-termini and a large, hydrophobic catalytic domain located in between. This gene affects oxidative stress as well as DNA damage and is a mediator of senescence.
It has been shown CDC6 shows proto-oncogenic activity. Cdc6 overexpression interferes with the expression of INK4/ARF tumor suppressor genes through a mechanism involving the epigenetic modification of chromatin at the INK4/ARF locus. In addition, CDC6 overexpression in primary cells may promote DNA hyperreplication and induce a senescence response similar to that caused by oncogene activation. These findings indicate that deregulation of CDC6 expression in human cells poses a serious risk of carcinogenesis.
THCA synthase is expressed in the glandular trichomes of Cannabis sativa. THCA synthase may contribute to the self-defense of Cannabis plants by producing THCA and hydrogen peroxide, which are both cytotoxic. Because these products are toxic to the plant, THCA synthase is secreted into the trichome storage cavity. THCA also acts as a necrosis-inducing factor by opening mitochondrial permeability transition pores, inhibiting mitochondrial viability and resulting in senescence in leaf tissues.
In captivity, lemurs can live twice as long as they do in the wild, benefiting from consistent nutrition that meets their dietary requirements, medical advancements, and improved understanding of their housing requirements. In 1960, it was thought that lemurs could live between 23 and 25 years. We now know that the larger species can live for more than 30 years without showing signs of aging (senescence) and still be capable of reproduction.
However, germ line and stem cells prevent the end replication problem with the help of telomerase. Telomerase elongates the 3’ end that is then formed into a t-loop to prevent the cell from entering the G0 phase and cell senescence. Inflammation and damage to tissue are the underlying problems due to increased senescent cells. In several studies shortened telomeres have been associated with age related sarcopenia, atherosclerotic cardiovascular disease, and cancer.
The growth factors TGF alpha, TGF beta, and IL2 have all been shown to stimulate c-Fos, and thereby stimulate cellular proliferation via AP-1 activation. Cellular senescence has been identified as "a dynamic and reversible process regulated by (in)activation of a predetermined enhancer landscape controlled by the pioneer transcription factor AP-1", which "defines the organizational principles of the transcription factor network that drives the transcriptional programme of senescent cells".
Knockdown of MRE11 in various human cancer cell lines has also been associated with a 3-fold increase in the level of p16INK4a tumor suppressor protein, which is capable of inducing cellular senescence and subsequently halting tumor cell proliferation. This is thought primarily to be the result of methylation of the p16INK4 promotor gene by MRE11. These data suggest maintaining the integrity and normal expression levels of MRN provides a protective effect against tumorigenesis.
"Microbial heterotrophic metabolic rates constrain the microbial carbon pump." The American Association for the Advancement of Science, 2011. In general, dissolved organic carbon (DOC) is introduced into the ocean environment from bacterial lysis, the leakage or exudation of fixed carbon from phytoplankton (e.g., mucilaginous exopolymer from diatoms), sudden cell senescence, sloppy feeding by zooplankton, the excretion of waste products by aquatic animals, or the breakdown or dissolution of organic particles from terrestrial plants and soils.
Reduced expression of MECP2 in Mecp2+/- neural stem cells causes an increase in senescence, impairment of proliferative capacity and accumulation of unrepaired DNA damages. After treatment of Mecp2+/- cells with either of three different DNA damaging agents, the cells accumulated more DNA damages and were more prone to cell death than control cells. It was concluded that reduced MECP2 expression causes reduced capacity to repair DNA and this likely contributes to neurological decline.
The two polyps thus created then generate their missing body parts and exoskeleton. Transversal division occurs when polyps and the exoskeleton divide transversally into two parts. This means one has the basal disc (bottom) and the other has the oral disc (top); the new polyps must separately generate the missing pieces. Asexual reproduction offers the benefits of high reproductive rate, delaying senescence, and replacement of dead modules, as well as geographical distribution.
Further analysis found a second TATA box 558 bp upstream of SER3. A bioinformatic scan identified this same TATA box element in related Saccharomyces. SRG1 has been found to be cis-acting, it had no repressive effect when in trans. SRG1 RNA is unrelated to Senescence Related Gene 1 (SRG1), a protein-coding gene found in Arabidopsis thaliana, and is also distinct from Stress Response Gene 1 (SRG1) found in Medicago sativa.
They proposed a cytochemical assay based on production of a blue-dyed precipitate that results from the cleavage of the chromogenic substrate X-Gal, which stains blue when cleaved by galactosidase. Since then, even more specific quantitative assays were developed for its detection at pH 6.0. Today this phenomenon is explained by the overexpression and accumulation of the endogenous lysosomal beta- galactosidase specifically in senescent cells. Its expression is not required for senescence.
She pursued graduate education in biology at Harvard University, where she became Nancy Kleckner's first graduate student. At Harvard, she was excited by a lecture by Jack Szostak, Nobel laureate in 2016, about his work on telomeres with Elizabeth Blackburn. She began a postdoctoral fellowship in 1983, working with Jack Szostak on yeast with a defective telomerase that underwent early senescence. She continued her study of telomeres as a postdoctoral fellow in Elizabeth Blackburn's laboratory.
Annual Review of Entomology, 50: 125-151. Symptoms of hopperburn resembles plant senescence and include necrosis around the feeding sites, which may cause leaves to prematurely drop, and chlorosis occurring at the leaf margins and around the leaf veins].] This feeding behavior can lead to significant monetary losses for growers of vegetables and crops as hopperburn can reduce the quantity of crops by stunting young plant growth and can reduce overall yield.Atakan, E. 2009.
Although oxidative phosphorylation is a vital part of metabolism, it produces reactive oxygen species such as superoxide and hydrogen peroxide, which lead to propagation of free radicals, damaging cells and contributing to disease and, possibly, aging (senescence). The enzymes carrying out this metabolic pathway are also the target of many drugs and poisons that inhibit their activities. It is the terminal process of cellular respiration in eukaryotes and accounts for high ATP yield.
Growth arrest and DNA-damage-inducible protein GADD45 gamma is a protein that in humans is encoded by the GADD45G gene on chromosome 9. GADD45G is also known as CR6, DDIT2, GRP17, OIG37, and GADD45gamma. GADD45G is involved in several different processes, including sexual development, human-specific brain development, tumor suppression, and the cellular stress response. GADD45G interacts with several other proteins that are involved in DNA repair, cell cycle control, apoptosis, and senescence.
Beecher was a leading proponent of Neo-Lamarckism (epitomized by Edward Drinker Cope and Alpheus Hyatt) and also argued for orthogenesis and racial senescence. Beecher’s promotion path at Yale was rapid. Promoted to Professor of Historical Geology at SSS in 1897 and, on the death of Marsh in 1899, Beecher succeeded him as Curator of the Geological Collections, Yale Peabody Museum. Beecher's title at SSS was later renamed University Professor of Paleontology.
Studies on several cell types have shown that ApoD expression can be induced by several stressing situations such as growth arrest, senescence, oxidative and inflammatory stresses. ApoD expression is also increased in several neuropathologies. ApoD expression is modulated in several pathologies such as HDL familial deficiency, Tangier disease, LCAT familial deficit and type 2 diabetes. It is overexpressed in numerous cancers, including breast, ovary, prostate, skin and central nervous system (CNS) cancer.
The extra muscle nuclei obtained by a strength training episode, seems to be very long lasting, perhaps permanent, even in muscles that are inactive for a long time. The ability to recruit new nuclei is impaired in the elderly,(Schultz & Lipton, 1982) so it might be beneficial to strength train before senescence. Doping with anabolic steroids also seem to act partly by recruiting new nuclei.Kadi F, Eriksson A, Holmner S & Thornell LE. (1999).
Annuality and perenniality are complex traits involving many underlying, often quantitative, genotypic and phenotypic factors. They are often determined by a trade-off between allocation to sexual (flower) structures and asexual (vegetative) structures. Switches between the annual and perennial habit are known to be common among herbaceous angiosperms. Increased allocation to reproduction early in life generally leads to a decrease in survival later in life (senescence); this occurs in both annual and perennial semelparous plants.
The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damages. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear DNA damage can contribute to aging, nuclear DNA is the main subject of this analysis. Nuclear DNA damage can contribute to aging either indirectly (by increasing apoptosis or cellular senescence) or directly (by increasing cell dysfunction).
Cushion plants form large, low-growing mats that can grow up to in diameter. The typical form is a compact mass of closely spaced stems with minimal apical dominance that terminate in individual rosettes. Each stem grows at a consistent rate so that no one rosette is more exposed than the rest of the cushion. Observations on senescence have concluded that cushion plants typically die en masse rather than individual rosettes dying at separate times.
Thymic involution remains an evolutionary mystery since it occurs in most vertebrates despite its negative effects. Since it is not induced by senescence, many scientists have hypothesized that there may have been evolutionary pressures for the organ to involute. A few hypotheses are as follows: Developing T cells that interact strongly with antigen being presented within the thymus are induced to undergo programmed cell death. The intended effect is deletion of self- reactive T cells.
The only gene commercially used to provide insect protection that does not originate from B. thuringiensis is the Cowpea trypsin inhibitor (CpTI). CpTI was first approved for use cotton in 1999 and is currently undergoing trials in rice. Less than one percent of GM crops contained other traits, which include providing virus resistance, delaying senescence, modifying flower colour and altering the plants composition. Golden rice is the most well known GM crop that is aimed at increasing nutrient value.
The eggs of heliothine moths tend to hatch within 3–10 days, dependent on how warm the temperature is. Eggs and pupae have the capacity to enter a diapause phase of overwintering if temperatures are too low for metamorphosis. By late winter and early spring, incoming warmer and drier weather usually signals the senescence of the seasons individuals and brings an influx of the lesser budworm in its moth stage. Favourable wind patterns and warm nights extend their migration.
Lysophosphatidylethanolamine (LPE) is a minor membrane glycerolipid; however, it has been reported that it has useful physiological effects on fruit and vegetable crops. LPE was approved by the United States Environmental Protection Agency for use on agricultural crops. It is used with tomatoes, peppers, grapes, cranberry, and oranges for increasing color, sugar contents and their storage life. In addition, it is reported that LPE can delay senescence in leaves and fruits, and mitigate stress of ethylene-induced process.
Proceedings – symposium on ecology and management of riparian shrub communities; 1991 May 29–31; Sun Valley, ID. Gen. Tech. Rep. INT-289. Ogden, UT: U.S. Department of Agriculture, Forest Service, Intermountain Research Station: 100–110 Green grasses are apparently a staple from late winter until just prior to grass senescence and Townsend ground squirrel estivation, when seeds become the primary diet item. Seeds are an important source of calories just prior to estivation.Rickart, Eric Allan. 1982.
P. aeruginosa. P. aeruginosa have self-immunity to their own effector toxins: Tsi proteins bind and stabilise Tse toxins, preventing cell senescence and peptidoglycan cell wall lysis. A wide range of Gram-negative bacteria have been shown to have antibacterial T6SSs, including opportunistic pathogens such as Pseudomonas aeruginosa, obligate commensal species that inhabit the human gut (Bacteroides spp.), and plant-associated bacteria such as Agrobacterium tumefaciens. These systems exert antibacterial activity via the function of their secreted substrates.
Gibberellins (GAs) are plant hormones that regulate various developmental processes, including stem elongation, germination, dormancy, flowering, flower development, and leaf and fruit senescence. GAs are one of the longest-known classes of plant hormone. It is thought that the selective breeding (albeit unconscious) of crop strains that were deficient in GA synthesis was one of the key drivers of the "green revolution" in the 1960s, a revolution that is credited to have saved over a billion lives worldwide.
The protein encoded by this gene is a helix-loop- helix (HLH) protein that can form heterodimers with members of the basic HLH family of transcription factors. The encoded protein has no DNA binding activity and therefore can inhibit the DNA binding and transcriptional activation ability of basic HLH proteins with which it interacts. This protein may play a role in cell growth, senescence, and differentiation. Two transcript variants encoding different isoforms have been found for this gene.
In vitro, when cells approach the Hayflick limit, the time to senescence can be extended by inactivating the tumor suppressor proteins - p53 and Retinoblastoma protein (pRb). Cells that have been so- altered eventually undergo an event termed a "crisis" when the majority of the cells in the culture die. Sometimes, a cell does not stop dividing once it reaches a crisis. In a typical situation, the telomeres are shortened and chromosomal integrity declines with every subsequent cell division.
Due to the heterogeneous nature of senescent cells, different immune system cells eliminate different senescent cells. Specific components of the senescence-associated secretory phenotype (SASP) factors secreted by senescent cells attract and activate different components of both the innate and adaptive immune system. Natural killer cells (NK cells) and macrophages play a major role in clearance of senescent cells. Natural killer cells directly kill senescent cells, and produce cytokines which activate macrophages which remove senescent cells.
However, if the transplant is performed at ages older than 10, two-year survival rates drop to 54%. A recent report by Zhang et al. investigates the mechanism of bone marrow failure in FANCC-/- cells. They hypothesize and successfully demonstrate that continuous cycles of hypoxia- reoxygenation, such as those seen by haemopoietic and progenitor cells as they migrate between hyperoxic blood and hypoxic marrow tissues, leads to premature cellular senescence and therefore inhibition of haemopoietic function.
Bidder's research focused on sponges, especially their hydraulics. He also studied the movements bottom feeders, as well as marine geology, in particular coastal erosion. In 1932, Bidder made a major contribution to the field of biogerontology by proposing that senescence was the effect of a "regulator" responsible for ending growth. This theory, known as "Bidder's hypothesis" has been refuted in numerous experiments, starting with Alex Comfort's 1963 study on guppy, a species that ages while growing.
The fruits are woody and persistent, which means they are retained on the plant after senescence. The seeds are kept within the dry fruit for a long period, they are released one to two years after the flowers were formed, and are spread through means of the wind. It is easily mistaken for the reed-like type of plants known as restios, with which it shares its habitat, and thus has often been overlooked in surveys of local flora.
The phosphorylation of Rb by CDK4/6 and CDK2 dissociates the Rb-repressor complex and serves as an on/off switch for the cell cycle. Once Rb is phosphorylated, the inhibition is released on the E2F transcriptional activity. This allows for the transcription of S phase genes encoding for proteins that amplify the G1 to S phase switch. Many different stimuli apply checkpoint controls including TGFb, DNA damage, contact inhibition, replicative senescence, and growth factor withdrawal.
The corolla of a plant refers to its set of petals. Corolla development in plants is broken into phases from anthesis to corolla wilting. The development of the corolla is directed in part by ethylene, though its concentration is highest when the plant is fertilized and no longer requires the production or maintenance of structures and compounds that attract pollinators. The role of ethylene in the developmental cycle is as a hormonal director of senescence in corolla tissue.
He also found that large populations of astrocytes negative to classical marker GFAP but positive to glutamine synthetase or S100B protein do not show hypertrophic changes in the aged brain thus suggesting that brain senescence is not associated with widespread astrogliosis. He also performed first detailed analysis of functional properties of glutamate transporters, glutamate and purinoceptors in old astrocytes in situ and found that brain ageing is associated with significant decrease in the density of these signalling molecules.
Since volume grows faster than surface area, this controls the ultimate size of the organism. Alfred Russel Wallace wrote this in a letter to E. B. Poulton in 1865.see Finch, C. 1990 Longevity, senescence, and the genome Univ Chicago Press Appendix 3 The surface area that is of importance is the part that is involved in substrate uptake (e.g. the gut surface), which is typically a fixed fraction of the total surface area in an isomorph.
A cell strain is derived either from a primary culture or a cell line by the selection or cloning of cells having specific properties or characteristics which must be defined. Cell strains are cells that have been adapted to culture but, unlike cell lines, have a finite division potential. Non-immortalized cells stop dividing after 40 to 60 population doublings and, after this, they lose their ability to proliferate (a genetically determined event known as senescence).
In populations where extrinsic mortality is low, the drop in reproductive probability after maturity is less severe than in other cases. The mutation accumulation theory therefore predicts that such populations would evolve delayed senescence. One such example of this scenario can be seen when comparing birds to organisms of equivalent size. It has been suggested that their ability to fly, and therefore lower relative risk of predation, is the cause of their longer than expected life span.
WRKY transcription factors (pronounced ‘worky’) are proteins that bind DNA. They are transcription factors that regulate many processes in plants and algae (Viridiplantae), such as the responses to biotic and abiotic stresses, senescence, seed dormancy and seed germination and some developmental processesRushton PJ, Somssich IE, Ringler P, Shen QJ: WRKY transcription factors. Trends in plant science 2010, 15(5):247-258Bakshi and Oelmüller (2014) WRKY transcription factors: Jack of many trades in plants. Plant Signaling & Behavior. 9(1).
As a result, Septoria produces pycnidia, an asexual flask shaped fruiting body, on the leaves of potato and other tuber-bearing spp. causing small black to brown necrotic lesions ranging in size from 1-5mm. The necrotic lesions can fuse together forming large necrotic areas susceptible to leaf drop, early senescence, dieback, and dwarfing. Septoria malagutii has been found only in the Andean countries of Bolivia, Ecuador, Peru, and Venezuela at altitudes of near 3000 meters.
These relations are extensively discussed in the neo-Piagetian theories of cognitive development. During senescence, RT deteriorates (as does fluid intelligence), and this deterioration is systematically associated with changes in many other cognitive processes, such as executive functions, working memory, and inferential processes. In the theory of Andreas Demetriou, one of the neo-Piagetian theories of cognitive development, change in speed of processing with age, as indicated by decreasing RT, is one of the pivotal factors of cognitive development.
Loss of epidermal SOD2 in mice induced cellular senescence, which irreversibly arrested proliferation of a fraction of keratinocytes. In older mice SOD2 deficiency delayed wound closure and reduced epidermal thickness. Mutant mice with a connective tissue specific lack of SOD2 had a reduced lifespan and a premature onset of aging-related phenotypes such as weight loss, skin atrophy, kyphosis (curvature of the spine), osteoporosis, and muscle degeneration. SOD2 over- expression was found to extend lifespan in mice.
Climacteric is the final physiological process that marks the end of fruit maturation and the beginning of fruit senescence. Its defining point is a sudden rise in respiration of the fruit, and normally takes place without any external influences. After the climacteric period, respiration rates (noted by carbon dioxide production) return to or dip below the pre- climacteric rates. The climacteric event also leads to other changes in the fruit, including pigment changes and sugar release.
Progenitor cells have become a hub for research on a few different fronts. Current research on progenitor cells focuses on two different applications: regenerative medicine and cancer biology. Research on regenerative medicine has focused on progenitor cells, and stem cells, because their cellular senescence contributes largely to the process of aging. Research on cancer biology focuses on the impact of progenitor cells on cancer responses, and the way that these cells tie into the immune response.
The syncytiotrophoblast layer is the interface between the developing fetus and the maternal blood supply, which forms, together with the underlying basal membrane and the fetal endothelium the placental barrier. The placental barrier enables nutrient and waste exchange, while blocking maternal immune and other cells, particles and molecules from passing into the fetal blood circulation. Cytotrophoblasts are forced into senescence by fusion into the syncytiotrophoblast. Therefore, cytotrophoblast proliferation is necessary for growth and maintenance of the syncytiotrophoblast layer.
The average cell will divide between 50 and 70 times before cell death. As the cell divides the telomeres on the end of the chromosome get smaller. The Hayflick limit is the theoretical limit to the number of times a cell may divide until the telomere becomes so short that division is inhibited and the cell enters senescence. The phenomenon of limited cellular division was first observed by Leonard Hayflick, and is now referred to as the Hayflick limit.
The main large-scale disturbances in the northern Inland rainforest patches in British Columbia are infrequent periodic fires and insect outbreaks of the western hemlock looper (Lambdina fiscellaria lugubrosa). On a small scale, these forests are characterized by gap dynamics as results of senescence, heart rot and root rots. Avalanches, wind and snow loading can have varying effects from small-scale events like tree snapping to disturbances that affect large areas.Drinkwater, Bob; Stevenson, Susan K. (2011).
Downregulation of ATG5 protein and mutations in the Atg5 gene have also been linked with prostate, gastrointestinal and colorectal cancers as ATG5 plays a role in both cell apoptosis and cell cycle arrest. Upregulation of Atg5 on the other hand has been shown to suppress melanoma tumorigenesis through induction of cell senescence. ATG5 also plays a protective role in M. tuberculosis infections by preventing PMN-mediated immunopathology. An Atg5−/− mutation in mice is known to be embryonic lethal.
Mild hyperoxia shortens telomeres and inhibits proliferation of fibroblasts: a model for senescence? Experimental cell research 220, 186-193.Harley, C.B., and Villeponteau, B. (1995). Telomeres and telomerase in aging and cancer. Current Opinion in Genetics & Development 5, 249-255. Geron's academic collaborators Elizabeth Blackburn and Carol Greider later shared the 2009 Nobel prize in Physiology or Medicine with Jack Szostak for their early discovery of how chromosomes are protected by telomeres and the enzyme telomerase.
The International Day of Older Persons is observed on October 1 each year. On December 14, 1990 the United Nations General Assembly voted to establish October 1 as the International Day of Older Persons as recorded in Resolution 45/106.Resolution 45/106 The holiday was observed for the first time on October 1, 1991.Ideas for observing this day The holiday is celebrated by raising awareness about issues affecting the elderly, such as senescence and elder abuse.
An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells can therefore be grown for prolonged periods in vitro. The mutations required for immortality can occur naturally or be intentionally induced for experimental purposes. Immortal cell lines are a very important tool for research into the biochemistry and cell biology of multicellular organisms.
The neurohacking trend has been heavily commercialized, with companies such as Lumosity and CogniFit marketing games that allegedly optimize the performances of the brain as well as alleviate the symptoms of senescence-related cognitive decline and other neurodegenerative disorders. Several studies have called into question the effectiveness of these softwares. The Federal Trade Commission (FTC) has filed claims against some companies producing brain training software for misleading marketing. Claims against Lumosity for misleading advertisement are over $2 million.
The network theory of aging supports the idea that multiple connected processes contribute to the biology of aging. Kirkwood and Kowald helped to establish the first model of this kind by connecting theories and predicting specific mechanisms. In departure of investigating a single mechanistic cause or single molecules that lead to senescence, the network theory of aging takes a systems biology view to integrate theories in conjunction with computational models and quantitative data related to the biology of aging.
In an expansion of their research on adult neurogenesis, the laboratory of Zupanc discovered the first vertebrate organism that lacks any of the hallmarks of brain senescence common to humans and all mammalian species examined thus far. In contrast to the latter, brown ghost knifefish (Apteronotus leptorhynchus) do not exhibit any significant age-related decline in stem/progenitor cell proliferation, neuronal and glial differentiation, or long-term survival of newly generated cells. The availability of this first vertebrate model of ‘negligible senescence’ provides unprecedented opportunities for a better understanding of the biology of aging and of the cellular mechanisms that protect brains from senescing. As the first investigator in the field of adult neurogenesis, Zupanc and his laboratory succeeded in generating three-dimensional, high- resolution maps of adult stem cells and their progeny, as well as molecular profiles of these cells, in the spinal cord. This work led to the development of a novel mapping approach (‘statistical mapping’), which enables researchers to produce global maps of central nervous system structures with cellular resolution.
Although chondrocyte senescence occurs with aging, mitotic figures are not seen in normal adult articular cartilage. The structure, density, and synthetic activity of an adult chondrocyte are various according to its position. Flattened cells are oriented parallel to the surface, along with the collagen fibers, in the superficial zone, the region of highest cell density. In the middle zone, chondrocytes are larger and more rounded and display a random distribution, in which the collagen fibers also are more randomly arranged.
BHLHE41 has been shown to suppress the expression of vascular endothelial growth factor (VEGF) in sarcoma cells and oral cancer cells. BHLHE41 also suppresses cytochrome P450 2D6 (CYP2D6) in hepatocellular carcinoma cells. While BHLHE40 induces apoptosis, senescence, and epithelial-mesenchymal transition (EMT) in tumor cells, BHLHE41 shows a circadian expression and inhibits EMT, apoptosis, and metastasis in sarcoma cells and hepatocellular carcinoma cells. It has been shown that the normal tissue adjacent to colon carcinomas show high levels of BHLHE41 expression.
Zeatin, a cytokinin Cytokinins or CKs are a group of chemicals that influence cell division and shoot formation. They also help delay senescence of tissues, are responsible for mediating auxin transport throughout the plant, and affect internodal length and leaf growth. They were called kinins in the past when they were first isolated from yeast cells. Cytokinins and auxins often work together, and the ratios of these two groups of plant hormones affect most major growth periods during a plant's lifetime.
Cysteine proteases play multifaceted roles, virtually in every aspect of physiology and development. In plants they are important in growth and development and in accumulation and mobilization of storage proteins such as in seeds. In addition, they are involved in signalling pathways and in the response to biotic and abiotic stresses. In humans and other animals, they are responsible for senescence and apoptosis (programmed cell death), MHC class II immune responses, prohormone processing, and extracellular matrix remodeling important to bone development.
This bud induction can be pinpointed to differentiation of a specific single cell, and thus is a very specific effect of cytokinin. Cytokinins have been shown to slow aging of plant organs by preventing protein breakdown, activating protein synthesis, and assembling nutrients from nearby tissues. A study that regulated leaf senescence in tobacco leaves found that wild-type leaves yellowed while transgenic leaves remained mostly green. It was hypothesized that cytokinin may affect enzymes that regulate protein synthesis and degradation.
In 1940, Jane Sherman married Ned Lehac, a high school Science Teacher who was also a composer and lyricist for revues, contributing material to 14 shows from 1930 to 1942. In the 1990s they moved together to the Lillian Booth Actors Home, run by the Actors Fund, where he died in 1999, aged 99. In 2003, Jane began publishing poems, gathering them into little books, some of which commented on aging. In a poem from her self-published book "Songs of Senescence".
Chinese scientists published a draft genome of Ginkgo biloba in 2016. The tree has a large genome of 10.6 billion DNA nucleobase "letters" (the human genome has three billion) and about 41,840 predicted genes which enable a considerable number of antibacterial and chemical defense mechanisms. In 2020, a study in China of gingko trees up to 667 years old showed little effects of aging, finding that the trees continued to grow with age and displayed no genetic evidence of senescence.
The majority of GM crops have been modified to be resistant to selected herbicides, usually a glyphosate or glufosinate based one. In 2014, 154 million hectares were planted with a herbicide resistant crop and 78.8 million hectares had insect resistant. This include 51.4 million hectares planted in thirteen countries that contained both herbicide tolerance and insect resistance. Less than one million hectares contained other traits, which include providing virus resistance, delaying senescence, modifying flower colour and altering the plants composition.
The tobacco budworm goes through 4 life stages: egg, larval, pupal, and adult. The life cycle generally occurs during the warmer months of late spring to early fall, depending on the region that the budworm is found. During this time, Heliothis virescens can undergo around 4 to 5 generations depending on the region. For larval, pupal, and adult stages, warmer temperatures encourage faster maturation but also faster senescence, while colder climates allow the budworm to mature at a slower rate.
The same model suggested that B. prionotes is quite susceptible to reductions in fire intervals. On the other hand, it shows little susceptibility to increases in fire interval: although senescence and death are often observed in plants older than about 30 years, healthy stands have been observed that have escaped fire for 50 years. These stands have a multi-aged structure, demonstrating the occurrence of successful inter-fire recruitment. Fire response may also furnish an explanation for the evolution of this species.
Morphological characteristics of pyknosis and other forms of nuclear destruction Apoptosis Karyorrhexis (from Greek κάρυον karyon, "kernel, seed or nucleus", and ῥῆξις rhexis, "bursting") is the destructive fragmentation of the nucleus of a dying cell whereby its chromatin is distributed irregularly throughout the cytoplasm. It is usually preceded by pyknosis and can occur as a result of either programmed cell death (apoptosis), cellular senescence, or necrosis. In apoptosis, the cleavage of DNA is done by Ca2+ and Mg2+ -dependent endonucleases.
The lesions exhibit pronounced concentric ridges with 1 to 3 erumpent black pycnidia within the central ring. Other symptoms on the leaves include: the lesions often fusing together to create large necrotic areas, making the leaves brittle and susceptible to leaf drop or wind damage. Additionally, the stems can become discolored and resemble bark and the whole plant can exhibit dwarfing, early senescence, and dieback. Stem lesions are more elongated than leaf lesions reaching up to 15mm in length and 2mm in diameter.
Cells from people with A–T demonstrate genomic instability, slow growth and premature senescence in culture, shortened telomeres and an ongoing, low-level stress response. These factors may contribute to the progeric (signs of early aging) changes of skin and hair sometimes observed in people with A–T. For example, DNA damage and genomic instability cause melanocyte stem cell (MSC) differentiation which produces graying. Thus, ATM may be a “stemness checkpoint” protecting against MSC differentiation and premature graying of the hair.
Chronic alcoholism decreases the levels of IGF1, which suppresses the ability of GH to increase bone mineral density. Increasing alcohol consumption is linked with decreasing testosterone and serum estradiol levels, which in turn lead to the activation of RANK (a TNF receptor) protein that promote osteoclast formation. Oxidative stress results when ethanol induces NOX expression, resulting in ROS production in osteoblasts which can ultimately result in cell senescence. Direct effects of chronic alcoholism are apparent in osteoblasts, osteoclasts and osteocytes.
Chronic systemic exposure of mice, rats, and Drosophila to D-galactose causes the acceleration of senescence (aging). It has been reported that high dose exposure of D-galactose (120 mg/Kg) can cause reduced sperm concentration and sperm motility in rodent and has been extensively used as an aging model when administered subcutaneous. Two studies have suggested a possible link between galactose in milk and ovarian cancer. Other studies show no correlation, even in the presence of defective galactose metabolism.
The cGAS–STING pathway is a component of the innate immune system that functions to detect the presence of cytosolic DNA and, in response, trigger expression of inflammatory genes that can lead to senescence or to the activation of defense mechanisms. DNA is normally found in the nucleus of the cell. Localization of DNA to the cytosol is associated with tumorigenesis, viral infection, and invasion by some intracellular bacteria. The cGAS – STING pathway acts to detect cytosolic DNA and induce an immune response.
The golden nematode negatively affects plants of the family Solanaceae by forming cysts on the roots of susceptible species. The cysts, which are composed of dead nematodes, are formed to protect the female's eggs and are typically yellow-brown in color. The first symptoms of infestation are typically poor plant growth, chlorosis, and wilting. Heavy infestations can lead to reduced root systems, water stress, and nutrient deficiencies, while indirect effects of an infestation include premature senescence and increased susceptibility to fungal infections.
This liberates E2F1 from its bound state in the cytoplasm and allows it to enter the nucleus. Once in the nucleus, E2F1 promotes the transcription of target genes that are essential for transition from G1 to S phase. This pathway connects the processes of tumor oncogenesis and senescence, fixing them on opposite ends of a spectrum. On one end, p16 hypermethylation, mutation, or deletion leads to downregulation of the gene and can lead to cancer through the dysregulation of cell cycle progression.
Davies research has been on the role of plant hormones in whole plant physiology, including stem growth, whole-plant senescence, tomato ripening and potato tuberization. In 1866, Gregor Mendel, the father of genetics, demonstrated that height in peas was controlled by a single factor. More than a century later, Davies discovered that Mendel's stem length gene (Le) in peas encoded a gibberellin 3β-hydroxylase. This enzyme converts GA20, an inactive form of gibberellin to GA1, the form of gibberellin that stimulates stem growth in peas.
Different speeds with which mortality increases with age correspond to different maximum life span among species. For example, a mouse is elderly at 3 years, a human is elderly at 80 years, and gingko trees show little effect of age even at 667 years. Almost all organisms senesce, including bacteria which have asymmetries between "mother" and "daughter" cells upon cell division, with the mother cell experiencing aging, while the daughter is rejuvenated. There is negligible senescence in some groups, such as the genus Hydra.
One major factor that affects wild guppies' senescence patterns is the mortality rate caused by predation. Guppies from high-predation environments suffer high extrinsic mortality rate because they are more likely to be killed by predators. Female guppies from high-predation habitats experience a significant increase in mortality at 6 months of age, while those from low-predation habitats do not suffer increased mortality until 16 months. However, guppies from high- predation environments were found to have longer lifespans because their reproductive lifespans are longer.
Telomestatin is a macrocyclic chemical compound that acts by inhibiting the telomerase activity of in vitro cancer cells. It was first isolated from the bacteria Streptomyces anulatus. Telomestatin induces the formation of basket- type G-quadruplex (G4) structures from hybrid-type G-quadruplexes in the telomeric region. Upon formation of G4 structure there will be a decrease in the activity of the telomerase, which is involved in the replication of the telomeres and as a result the cell dies due to Hayflick type senescence.
Ageing or aging (see spelling differences) is the process of becoming older. The term refers especially to human beings, many animals, and fungi, whereas for example bacteria, perennial plants and some simple animals are potentially biologically immortal. In the broader sense, aging can refer to single cells within an organism which have ceased dividing (cellular senescence) or to the population of a species (population ageing). In humans, aging represents the accumulation of changes in a human being over time and can encompass physical, psychological, and social changes.
During a controlled diatom bloom, TEP concentrations saw exponential growth during bloom growth, flocculation, and senescence, but the production of TEP did not increase after nutrient depletion. In fact, TEP concentration was found to be a linear function of chlorophyll a and POC, suggesting that TEP production is linked to phytoplankton growth. The ratio of TEP to phytoplankton was a determining factor in bloom flocculation. During flocculation, TEP, due to its high stickiness, aggregated with itself and phytoplankton, but phytoplankton did not independently flocculate to themselves.
Loss of telomeric DNA through repeated cycles of cell division is associated with senescence or somatic cell aging. In contrast, germ line and cancer cells possess an enzyme, telomerase, which prevents telomere degradation and maintains telomere integrity, causing these types of cells to be very long-lived. In humans, the role of subtelomere disorders is demonstrated in facioscapulohumeral muscular dystrophy (FSHD), Alzheimer's disease, and peculiar syndromic diseases (malformation and mental retardation). For example, FSHD is associated with a deletion in the subtelomeric region of chromosome 4q.
Clinically important research of gel based in vitro 3D model for the osteocytic potentiality of human CD34+ stem cells has been described. The results confirm that the human CD34+ stem cells possess unique osteogenic differentiation potential and can be used in the early regeneration of injured bone. Osteocytes die as a consequence of senescence, degeneration/necrosis, apoptosis (programmed cell death), and/or osteoclastic engulfment. The percentage of dead osteocytes in bone increases with age from less than 1% at birth to 75% after age 80.
Climate change is expected to alter the phenology, or timing of lifecycle events, of species worldwide. Environmental cues such as seasonal shifts in temperature and photoperiod influence processes such as germination, spring growth, breeding or flowering season, seed set, metamorphosis, migration, and senescence. Increasing winter and spring temperatures over the last century, particularly in northern latitudes, have resulted in rapid phenological shifts in many species. The magnitude and direction of these shifts are unpredictable and vary with latitude, topography, and the species in question.
Recent data suggests that an increased frequency of senescent CD8+ T cells in the peripheral blood is associated with the development of hyperglycemia from a pre-diabetic state suggestive of senescence playing a role in metabolic aging. Senescent Cd8+ T cells could be utilized as a biomarker to signal the transition from pre-diabetes to overt hyperglycemia. Recently, Hashimoto and coworkers profiled thousands of circulating immune cells from supercentenarians at single-cell resolution. They identified a very unique increase in cytotoxic CD4 T cells in these supercentenarians.
Senescent cells increase with aging, and senescent cells secrete a pro- inflammatory cocktail of chemicals, a condition known as senescence-associated secretory phenotype (SASP). Inflamm-aging has been also associated with persistent Cytomegalovirus infection. Cytomegalovirus drives up production of a variety of inflammatory cytokines and also results in expansion of CMV specific memory T cells. Other possible factors that may lead to inflamm-aging include overnutrition, altered gut microbiome, impaired intestinal epithlial barrier, and chronic stress occurring in any stage of the individual's life.
Gene Targeting In 2006, he published the first comprehensive in vivo quantification of cellular senescence in aging primates. That year, his lab also discovered how (through the Polycomb pathway) c-Myc contributes to the regulation of chromatin states. His research has found that mice missing one copy of the Myc transcription factor live longer than wild-type mice.Benefits of Missing MYC He is co-Editor-in-Chief of the journal Aging Cell, and is chair of the 2015 Gordon Research Conference on the Biology of Aging.
Herbaceous (non-wooded) vegetation dominates grasslands and, unlike forests, carbon is stored in the roots and soil underground. Furthermore, this above-ground biomass carbon is relatively short-lived due to grazing, fire, and senescence. In contrast, grassland species have an extensive fibrous root system, with grasses often accounting for 60-80% of the biomass carbon in this ecosystem. This underground biomass can extend several meters below the surface and store abundant carbon into the soil, resulting in deep, fertile soils with high organic matter content.
Furthermore, 14-3-3ζ may regulate glucose receptor trafficking in response to insulin levels through its interaction with IRS1. In addition to cell survival, 14-3-3ζ regulates cell cycle progression through various ligands and processes. For instance, 14-3-3ζ controls cellular senescence by complexing with BIS to chaperone protein folding of STAT3 and activate the signaling pathway. Also, 14-3-3ζ can negatively regulate the G2-M phase checkpoint by binding and sequestering the cyclin-dependent kinases to the cytoplasm, thus inhibiting their activity.
Bmi-1 is a subunit of the Polycomb Repressive Complex 1 (PRC1) and assists in preventing differentiation of stem cells. Though PRC1 isn't as well-studied as PRC2, Bmi-1 has had a great deal of focus for its involvement in numerous cancers. It has been found to regulate cell senescence and proliferation through repressing cell cycle regulating genes such as p16 and p19 (sometimes referred to as Ink4A/Arf locus). Normally, this function allows it to assist stem cells in maintaining their self-renewing capacity.
Catabiosis is the process of growing older, aging and physical degradation. The word comes from Greek "kata"--down, against, reverse and "biosis"--way of life and is generally used to describe senescence and degeneration in living organisms and biophysics of aging in general. One of the popular catabiotic theories is the entropy theory of aging, where aging is characterized by thermodynamically favourable increase in structural disorder. Living organisms are open systems that take free energy from the environment and offload their entropy as waste.
When leaves change color in the autumn, it is due to the loss of green chlorophyll, which unmasks preexisting carotenoids. In this case, relatively little new carotenoid is produced—the change in plastid pigments associated with leaf senescence is somewhat different from the active conversion to chromoplasts observed in fruit and flowers. There are some species of flowering plants that contain little to no carotenoids. In such cases, there are plastids present within the petals that closely resemble chromoplasts and are sometimes visually indistinguishable.
Some flowers will change color at the same rate regardless of pollinator visitation, while others can be induced by pollen deposition on the stigma. However, inducible flowers will eventually change color due to senescence even without pollinator activity. Depending on the species, floral color change can affect an entire flower or it can occur in localized parts. Previous research has found that moth-pollinated flowers are more likely to have whole flower color changes, while other insect-pollinated flowers are more likely to have localized color changes.
DNA-SCARS (short for DNA segments with chromatin alterations reinforcing senescence) are nuclear substructures with persistent DNA damage and DNA damage response proteins found in senescent cells. DNA-SCARS are associated with PML nuclear bodies and the accumulation of activated ATM, ATR, CHK2 and p53 proteins. DNA-SCARS lack most of the characteristics of transient, reversible DNA damage foci, such as single-stranded DNA, active DNA synthesis, and DNA repair proteins RPA and RAD51. Telomere dysfunction-induced foci (TIF) are generally associated with DNA-SCARS.
Continuing declines in the number of mature individuals, and number of locations and subpopulations are projected for several reasons including: lack of formal protection or management programs, the vulnerability of small populations to stochastic disturbance events (e.g. cyclones), ongoing competition with invasive weeds, predation by rats, senescence of over-mature plants, and sex ratio bias. The species is adapted to moist forest conditions and is therefore susceptible to unfavourable climate change (projected increases in the incidence of drought and extreme rainfall events that cause physical damage).
If increased telomerase activity is associated with malignancy, then possible cancer treatments could involve inhibiting its catalytic component, hTERT, to reduce the enzyme's activity and cause cell death. Since normal somatic cells do not express TERT, telomerase inhibition in cancer cells can cause senescence and apoptosis without affecting normal human cells. It has been found that dominant-negative mutants of hTERT could reduce telomerase activity within the cell. This led to apoptosis and cell death in cells with short telomere lengths, a promising result for cancer treatment.
Hannah M. Dee, Cohn, A. G. and Hogg, D. C. "Building semantic scene models from unconstrained video" Volume 116, Issue 3, March 2012, Pages 446.456 Paul Robson, Michal Mos, Hannah Dee, John Clifton-Brown and Iain Donnison (2011). Improving bioenergy crop yield and quality through manipulating senescence. In: Biomass and Bioenergy Crops IV. Aspects of Applied Biology 112, pp. 323–328. Hannah M. Dee & Paulo E. Santos (2011): The Perception and Content of Cast Shadows: An Interdisciplinary Review, Spatial Cognition & Computation, 11:3, 226–25.
The reliability theory of aging is an attempt to apply the principles of reliability theory to create a mathematical model of senescence. The theory was published in Russian by Leonid A. Gavrilov and Natalia S. Gavrilova as Biologiia prodolzhitelʹnosti zhizni in 1986, and in English translation as The Biology of Life Span: A Quantitative Approach in 1991. One of the models suggested in the book is based on an analogy with the reliability theory. The underlying hypothesis is based on the (previously suggested) premise that humans are born in a highly defective state.
From 2003–2009, Methuselah Foundation served as the backbone organization for the Strategies for Engineered Negligible Senescence (SENS) program, a long-term research framework developed by Aubrey de Grey. The SENS program aims to prevent or reverse seven forms of molecular or cellular damage associated with aging. During that time, de Grey and David Gobel established SENS-related research programs on human bioremedial biology – "getting the crud out" in Methuselah's parlance – at Rice University and Arizona State University. The programs were the first use of environmental remediation principles directed at reversing "pollution" in human cells.
The adult specimens of this protea are killed when they are caught in the wildfires which periodically pass through the native habitat, but the seeds can survive such events. Protea species which have adapted to frequent fire regimes in their habitat in such a manner are called 'reseeders', or, more technically, serotinous. The fruit are stored in the old, dried inflorescences, which are persistently retained on the plant after senescence, although they eventually fall off. According to Rourke, drought-stricken plants in their natural habitat shed their seeds much faster than those growing in cultivation.
Despite the fact that cellular senescence likely evolved as a means of protecting against cancer early in life, SASP promotes the development of late-life cancers. Cancer invasiveness is promoted primarily though the actions of the SASP factors metalloproteinase, chemokine, interleukin 6 (IL-6), and interleukin 8 (IL-8). In fact, SASP from senescent cells is associated with many aging-associated diseases, including not only cancer, but atherosclerosis and osteoarthritis. For this reason, senolytic therapy has been proposed as a generalized treatment for these and many other diseases.
In differentiated cells, which make up the majority of cells in the body and are assumed to be in irreversible G0, Rb maintains both arrest and differentiation. Loss of Rb therefore exhibits multiple different responses within different cells that ultimately all could result in cancer phenotypes. For cancer initiation, loss of Rb may induce cell cycle re-entry in both quiescent and post-mitotic differentiated cells through dedifferentiation. In cancer progression, loss of Rb decreases the differentiating potential of cycling cells, increases chromosomal instability, prevents induction of cellular senescence, promotes angiogenesis, and increases metastatic potential.
Regardless of whether the plots were fertilised or not, grazing by Neohelice granulata also reduced the length specific leaf growth rates of the leaves in summer, while increasing their length-specific senescence rates. This may have been assisted by the increased fungal effectiveness on the wounds left by the crabs.Alberti, J., Cebrian, J., Casariego, A. M., Canepuccia, A., Escapa, M. and Iribarne, O. (2011). "Effects of nutrient enrichment and crab herbivory on a SW Atlantic salt marsh" productivity. Journal of Experimental Marine Biology and Ecology, 405: 99–104.
Epigenetic medicine encompasses a new branch of neuroimmunology that studies the brain and behavior, and has provided insights into the mechanisms underlying brain development, evolution, neuronal and network plasticity and homeostasis, senescence, the etiology of diverse neurological diseases and neural regenerative processes. It is leading to the discovery of environmental stressors that dictate initiation of specific neurological disorders and specific disease biomarkers. The goal is to "promote accelerated recovery of impaired and seemingly irrevocably lost cognitive, behavioral, sensorimotor functions through epigenetic reprogramming of endogenous regional neural stem cells".
Thus, females try to enhance offspring survival by laying egg masses on cool moist slopes where host plant senescence is most delayed. Once the larvae reach the diapause stage and become post- diapause larvae, they must grow by basking in the sunlight to regulate their body temperature. Larval body temperature is about 10-12 °C (18-22 °F) above ambient temperature, and the fastest growth rate occurs at 30-35 °C (86-95 °F). They must receive enough insolation to terminate the diapause stage and become a fully-grown butterfly.
There are nine series of bracts surrounding the flower head, the outer ones being ovate in shape, with a rounded apex, and are covered in silky hairs and have a fringe of hairs along their margins (ciliate). The inner bracts are more oblong and concave in shape, also ciliate, but with less silky hairs, with the innermost bracts glabrous and the length of the flowers. The plant is monoecious with both sexes in each flower. The fruits are woody and persistent, which means they are retained on the plant after senescence.
Bureau of Land Management, California State Office. The fruit is a long, cylindrical capsule approximately 2 to 3 centimeters in length that matures May through July, becoming dry at full maturity with plant senescence. The fruits typically either do not open or only open part way near the tip and do not disperse most of the seed at maturity. It has been observed that most fruits fully open and seeds disperse with rain drop impact on the dry fruits - either during infrequent summer rain storms or with the first rains in fall.
The Yang cycle Ethylene is produced from essentially all parts of higher plants, including leaves, stems, roots, flowers, fruits, tubers, and seeds. Ethylene production is regulated by a variety of developmental and environmental factors. During the life of the plant, ethylene production is induced during certain stages of growth such as germination, ripening of fruits, abscission of leaves, and senescence of flowers. Ethylene production can also be induced by a variety of external aspects such as mechanical wounding, environmental stresses, and certain chemicals including auxin and other regulators.
One such motif, outspoken by Mitsurugi, is the discriminatory notion that marionettes are of no importance to humans beyond their menial labor, and should be disenfranchised to the affection or privileges of people. This idea becomes more recurrent later in the series when Otaru finds himself growing closer to the girls and questions himself for it. Another visited theme is the exploration of life, its senescence, and death. These truths have a major impact on the girls' developmental identity as they come to terms with themselves and humans.
Chlorophyll(ide) b reductase (), chlorophyll b reductase, Chl b reductase) is an enzyme with systematic name 71-hydroxychlorophyllide-a:NAD(P)+ oxidoreductase. This enzyme catalyses the following chemical reaction : 71-hydroxychlorophyllide a + NAD(P)+ \rightleftharpoons chlorophyllide b + NAD(P)H + H+ This enzyme carries out the first step in the conversion of chlorophyll b to chlorophyll a. It is involved in chlorophyll degradation, which occurs during leaf senescence, and it also forms part of the chlorophyll cycle, which interconverts chlorophyll a and b in response to changing light conditions.
However, there is more than one theory out there for aging. The competing model to explain senescence is Medawar's "mutation accumulation" hypothesis, saying that "over evolutionary time, late-acting mutations will accumulate at a much faster rate than early-acting mutation. These late-acting mutations will thus lead to declining viability and/or fertility as an organism ages." Medawar's theory is based around the older concept of selection shadow that had been discussed throughout the early 1900s and led to Medawar's theory after discussions with J. B. S. Haldane in the 1940s.
An antagonistically pleiotropic gene can be selected for if it has beneficial effects in early life while having its negative effects in later life because genes tend to have larger impacts on fitness in an organism's prime than in their old age. An example of this is testosterone levels in male humans. Higher levels of this hormone lead to increased fitness in early life, while causing decreased fitness in later life due to a higher risk for prostate cancer. This is an example of antagonistic pleiotropy being an explanation for senescence.
Passaging (also known as subculture or splitting cells) involves transferring a small number of cells into a new vessel. Cells can be cultured for a longer time if they are split regularly, as it avoids the senescence associated with prolonged high cell density. Suspension cultures are easily passaged with a small amount of culture containing a few cells diluted in a larger volume of fresh media. For adherent cultures, cells first need to be detached; this is commonly done with a mixture of trypsin- EDTA; however, other enzyme mixes are now available for this purpose.
Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2) is a gene located on human chromosome 12p11. It encodes a protein of 377 amino acid residues. ERGIC2 protein is also known as PTX1, CDA14 or Erv41. The biological function of ERGIC2 protein is unknown, although it was initially identified as a candidate tumor suppressor of prostate cancer, and has been shown to induce cell growth arrest and senescence, to suppress colony formation in soft agar, and to decrease invasive potential of human prostate cancer cell line (PC-3 cells).
Atropa baetica is one of the food plants of the larva of the Noctuid moth Heliothis peltigera Schiff. However, the toxicity of the leaves before the onset of senescence is such that the moth imagoes can display developmental abnormalities resulting from larval consumption of the plant e.g. deformities of the wings. The common name of H. peltigera in German (Bilsenkraut-Blüteneule) translates as 'the henbane-blossom owl (moth)', revealing the species' penchant for another plant in the Hyoscyameae – namely Hyoscyamus niger, black henbane – the chemistry of which is similar to that of Atropa baetica.
In general, dissolved organic carbon (DOC) is introduced into the ocean environment from bacterial lysis, the leakage or exudation of fixed carbon from phytoplankton (e.g., mucilaginous exopolymer from diatoms), sudden cell senescence, sloppy feeding by zooplankton, the excretion of waste products by aquatic animals, or the breakdown or dissolution of organic particles from terrestrial plants and soils. Bacteria in the microbial loop decompose this particulate detritus to utilize this energy-rich matter for growth. Since more than 95% of organic matter in marine ecosystems consists of polymeric, high molecular weight (HMW) compounds (e.g.
Specimens belonging to these species are subject to biological aging (or senescence), and loose their vitality. The maximum life expectancy differs between twenty-five to thirty years in smaller species like L. truncatulum and L. oleifolia, to fifty to eighty years in L. praemorsum. For this group of species, fire is a prerequisite to rejuvenate and so maintain the population. If the fires occur as frequent as every two or three year however, the soil seed bank gets depleted because no new seeds are added, and the species may locally disappear.
She completed her Ph.D. in molecular biology in 1987 at the University of California, Berkeley, under Elizabeth Blackburn. While at UC Berkeley, Greider co-discovered telomerase, a key enzyme in cancer and anemia research, along with Blackburn. Greider joined Blackburn's laboratory in April 1984 looking for the enzyme that was hypothesized to add extra DNA bases to the ends of chromosomes. Without the extra bases, which are added as repeats of a six base pair motif, chromosomes are shortened during DNA replication, eventually resulting in chromosome deterioration and senescence or cancer-causing chromosome fusion.
However, telomeres do not fully prevent the loss of coding DNA at the terminal ends of linear chromosomes. In fact, the eventual loss of coding DNA in cellular lines within an organism is thought to play a role in senescence. Furthermore, evidence suggests that telomeres can be unstable and can be prone to mutations which lead to tumor development. Mutations which lead to the constitutive activity of telomerase can result in the loss of cellular mortality in tumor cell lines, which is associated with the development of cancer.
A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc. Natl. Acad. Sci. USA 85, 6622–6626 (1988). in human white blood cells, and a semi- automated method for doing so was published in Nature Protocols. Telomere length in white blood cells has been a subject of interest because telomere length in these cell types (and also of other somatic tissues) declines gradually over the human lifespan, resulting in cell senescence, apoptosis,Harley, C.B., Futcher, A.B. & Greider, C.W. Telomeres shorten during ageing of human fibroblasts.
Often associated with aging and age-related diseases in vivo, senescent cells can be found in many renewable tissues, including the stroma, vasculature, hematopoietic system, and many epithelial organs. Resulting from accumulation over many cell divisions, senescence is often seen in age-associated degenerative phenotypes. Senescent fibroblasts in models of breast epithelial cell function have been found to disrupt milk protein production due to secretion of matrix metalloproteinases. Similarly, senescent pulmonary artery smooth muscle cells caused nearby smooth muscle cells to proliferate and migrate, perhaps contributing to hypertrophy of pulmonary arteries and eventually pulmonary hypertension.
Bast, F., Shimada, S., Hiraoka, M., & Okuda, K. 2009. Asexual life history by biflagellate zoids in Monostroma latissimum (Ulotrichales). Aquatic Botany, 91: 213-218. Patterns of seasonal fluctuations in its thallus lengths were habitat specific and recur annually.Bast, F., Shimada, S., Hiraoka, M., & Okuda, K. 2009. Seasonality and thallus ontogeny of edible seaweed Monostroma latissimum (Kützing) Wittrock (Chlorophyta, Monostromataceae) from Tosa Bay, Kochi, Japan. Hydrobiologia, 630: 161-167. Both appearance and decay of thalli were earlier at high saline habitats, suggesting that salinity positively influences either maturation of sporophytes or senescence of gametophytes.
The ability of E. solidaginis to survive the freezing temperatures of winter has been the subject of much research. In response to dropping temperatures and the senescence of surrounding plant tissues, the larva begins to synthesize and accumulate sorbitol and glycerol in its tissues. These compounds help protect the larvae against freezing damage by lowering the melting point of their bodily fluids, thus reducing the amount of ice that can form. Aquaporins, membrane proteins involved in the channeling of water, have also been shown to play a key role in E. solidaginis’ freezing tolerance.
In addition to the core histones, H2A, H2B, H3, and H4, there are other versions of the histone proteins that can be significantly different in their sequence and are important for regulating chromatin dynamics. Histone H3.3 is a variant of histone H3 that is incorporated into the genome independent of replication. It is the major form of histone H3 seen in the chromatin of senescent human cells, and it appears that excess H3.3 can drive senescence. There are multiple variants of histone 2, the one most notably implicated in aging is macroH2A.
In the literature, mega-telomeres are referred to as Class III telomeres based on the characteristics of their arrays. Many studies in model organisms have established the significance of telomere structure and function in regulating genome stability, cellular aging, and oncogenesis. It has been suggested that mega-teleomeres may serve as protective mechanism against senescence in long-lived organisms. However, there is some debate on the topic, since telomeric length does not seem to affect lifespan in mice and birds with both long and short life-spans have been shown to have mega-telomeres.
Aisenberg & Costa (2008) In captivity, these spiders have been maintained from wild-collected eggs to maturity and senescence in petri dishes, one spider per dish. A thin layer of sea sand and a watered lump of clean cotton wool create a favorable microclimate and allow the spiders to drink. Spiderlings fared well in dishes of 3.5 cm diameter and about 1 cm height; as they grow (around the third to fourth instar) they will need to be housed in larger dishes (about 10 cm in diameter and over 1 cm in height).
Flight of the adult codling moths starts near the beginning of May with the eclosion of second generation moths and stops around the end of August as the first generation moths reach senescence every year. The first and second generation flight period overlap anywhere from 10 to 20 days. Overlap of second and first generation moth flight period means there will be continuous damage done by the codling moth during the summer months. Adult moths are generally sedentary and tend to spend the day resting on leaves or branches.
Furthermore, it acts in a fully reversible manner, readily converting 5-oxo- ETE back to 5(S)-HETE. Since cells typically maintain very high levels of NADPH compared to their NADP+ levels, they generally have little or no ability to convert 5(S)-HEE to 5-oxo-ETE, and when confronted with 5-oxo-ETE rapidly metabolize it to 5(S)-HETE. However, cells undergoing aging, senescence, apoptosis, oxidative stress, or other conditions that raise their levels of reactive oxygen species (e.g. superoxide anion, oxygen radicals, and peroxides) either physiologically (e.g.
As part of the DNA damage response during induction of cellular senescence, cells upregulate the expression of NKG2D ligands that enable NK-mediated killing of senescent cells via the granule exocytosis pathway.Sagiv A, Biran A, Yon M, Simon J, Lowe SW, Krizhanovsky V. (2013). Granule exocytosis mediates immune surveillance of senescent cells Oncogene, 32, 1971–197, doi:10.1038/onc.2012.206 Specifically, MICA and ULBP2 proteins on senescent cells are recognized by the NKG2D receptor on Natural Killer cells, which is necessary for efficient recognition and elimination of senescent cells.
Cysteine-rich angiogenic inducer 61 (CYR61) or CCN family member 1 (CCN1), is a matricellular protein that in humans is encoded by the CYR61 gene. CYR61 is a secreted, extracellular matrix (ECM)-associated signaling protein of the CCN family (CCN intercellular signaling protein). CYR61 is capable of regulating a broad range of cellular activities, including cell adhesion, migration, proliferation, differentiation, apoptosis, and senescence through interaction with cell surface integrin receptors and heparan sulfate proteoglycans. During embryonic development, CYR61 is critical for cardiac septal morphogenesis, blood vessel formation in placenta, and vascular integrity.
Murine models instead require induction of typical anaemic phenotypes by elevated dosing with MMC that does not affect wild-type animals, before they can be used experimentally as preclinical models for bone marrow failure and potential stem cell transplant or gene therapies. Both female and male mice homozygous for a FANCA mutation show hypogonadism and impaired fertility. Homozygous mutant females exhibit premature reproductive senescence and an increased frequency of ovarian cysts. In spermatocytes, the FANCA protein is ordinarily present at a high level during the pachytene stage of meiosis.
ROS is a double-edged sword. On one hand, at low levels, ROS facilitates cancer cell survival since cell-cycle progression driven by growth factors and receptor tyrosine kinases (RTK) require ROS for activation and chronic inflammation, a major mediator of cancer, is regulated by ROS. On the other hand, a high level of ROS can suppress tumor growth through the sustained activation of cell-cycle inhibitor and induction of cell death as well as senescence by damaging macromolecules. In fact, most of the chemotherapeutic and radiotherapeutic agents kill cancer cells by augmenting ROS stress.
These functions then allow DNAJA3 to mediate mitochondrial fission through DRP1 and, by extension, cellular processes such as cell movement, growth, proliferation, differentiation, senescence, and apoptosis. However, though both isoforms of DNAJA3 are involved with cell survival, they are also observed to influence two opposing outcomes. The proapoptotic long isoform induces apoptosis by stimulating cytochrome C release and caspase activation in the mitochondria, whereas the antiapoptotic short isoform prevents cytochrome C release and, thus, apoptosis. In neuromuscular junctions, only the short isoform clusters acetylcholine receptors for efficient synaptic transmission.
Cancer can be seen as a disruption of normal restriction point function, as cells continually and inappropriately reenter the cell cycle, and do not enter G0. Mutations at many steps in the pathway towards the restriction point can result in cancerous growth of cells. Some of the genes most commonly mutated in cancer include Cdks and CKIs; overactive Cdks or underactive CKIs lower the stringency of the restriction point, allowing more cells to bypass senescence. The restriction point is an important consideration in the development of new drug therapies.
Linear motif mediated protein-protein interactions have shown promise in recent years as novel drug targets. Success stories include the MDM2 motif analog Nutlin-3 and integrin targeting RGD-mimetic Cilengitide: Nutlin-3 antagonises the interaction of MDM2's SWIB domain with p53 thus stabilising p53 and inducing senescence in cancer cells. Cilengitide inhibits integrin-dependent signaling, causing the disassembly of cytoskeleton, cellular detachment and the induction of apoptosis in endothelial and glioma cells. In addition, peptides targeting the Grb2 and Crk SH2/ SH3 adaptor domains are also under investigation.
FOXO transcription factors have been shown to be the down downstream effector molecules of insulin-like growth factor (IGF) signaling pathway. In the absence of insulin, PI3K is inactive, so the FOXO homolog daf-16 is able to translocate to the nucleus and turn on many genetic pathways associated with longevity in the roundworm Caenorhabditis elegans. FOXO's activation of these pathways produces an increase in lifespan for worms, flies, mice; similar variants of FOXO3a have been associated with longer human lives as well. FOXO4 can bind with p53 protein to induce cellular senescence.
Studies are also underway to understand if there is a relation between these pathologies or these mutations and a predisposition to cancer. Currently proposed mechanisms by which POLD1 defects are pathogenic focus on the idea of replication defects leading to genomic instability and checkpoint activation, ultimately leading to cell death or cellular senescence. Alternatively, Polδ is associated with lamins and the nuclear envelope during G1/S arrest or early S phase; mutations in lamins cause nuclear envelope-related lipodystrophies with phenotypes similar to MDPL/MDP and Werner’s syndrome.
Heat shock 70 kDa protein 1L is a protein that in humans is encoded by the HSPA1L gene on chromosome 6. As a member of the heat shock protein 70 (Hsp70) family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins. Its functions contribute to biological processes including signal transduction, apoptosis, protein homeostasis, and cell growth and differentiation. It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence and aging, and Graft-versus-host disease.
This species has also been involved in the rotting of strawberry blossoms. Infection of strawberry blossoms by C. cladosporioides has been associated with simultaneous infections by Xanthomonas fragariae (in California), and more recently C. tenuissimum (in Korea). C. cladosporioides infects the anthers, sepals, petals and pistils of the strawberry blossom and is typically observed on older flowers with dehisced anthers and signs of senescence. From 1997-2000, there was a higher proportion of misshapen fruits due to C. cladosporioides infection, and their culling affected the strawberry industry in California.
The biomedical gerontologist Aubrey de Grey has initiated a project, Strategies for Engineered Negligible Senescence (SENS), to study how to reverse the damage caused by aging. He has proposed seven strategies for what he calls the seven deadly sins of aging: # Cell loss can be repaired (reversed) just by suitable exercise in the case of muscle. For other tissues it needs various growth factors to stimulate cell division, or in some cases it needs stem cells. # Senescent cells can be removed by activating the immune system against them.
The arrows with flat heads are a notation meaning "inhibits," used in the literature of gene expression and gene regulation. The ultimate objective of SENS is the eventual elimination of age- related diseases and infirmity by repeatedly reducing the state of senescence in the organism. The SENS project consists in implementing a series of periodic medical interventions designed to repair, prevent or render irrelevant all the types of molecular and cellular damage that cause age- related pathology and degeneration, in order to avoid debilitation and death from age-related causes.
ACF1 and NuRD are downregulated in senescent cells which suggests that chromatin remodeling is essential for maintaining a mitotic phenotype. Genes involved in signaling for senescence can be silenced by chromatin confirmation and polycomb repressive complexes as seen in PRC1/PCR2 silencing of p16. Specific remodeler depletion results in activation of proliferative genes through a failure to maintain silencing. Some remodelers act on enhancer regions of genes rather than the specific loci to prevent re-entry into the cell cycle by forming regions of dense heterochromatin around regulatory regions.
Senescent cells undergo widespread fluctuations in epigenetic modifications in specific chromatin regions compared to mitotic cells. Human and murine cells undergoing replicative senescence experience a general global decrease in methylation; however, specific loci can differ from the general trend. Specific chromatin regions, especially those around the promoters or enhancers of proliferative loci, may exhibit elevated methylation states with an overall imbalance of repressive and activating histone modifications. Proliferative genes may show increases in the repressive mark H3K27me3 while genes involved in silencing or aberrant histone products may be enriched with the activating modification H3K4me3.
When considering food storage and preservation, the technologies of modified atmosphere and controlled atmosphere are widely used for the storage and packing of several types of foods. They offer several advantages such as delay of ripening and senescence of horticultural commodities, control of some biological processes such as rancidity, insects, bacteria and decay, among others. Controlled atmosphere (CA) storage refers to atmospheres that are different than normal air and strictly controlled at all times. This type of storage manipulates the CO2 and O2 levels within airtight stores of containers.
A male Nothobranchius furzeri GRZ (from Gonarezhou National Park) Some strains have a lifespan as short as several months and can thus serve as a model for biogerontological studies. The African turquoise killifish (Nothobranchius furzeri) is the shortest- living vertebrate that can be bred in captivity, having a lifespan of between three and nine months. Sexual maturation occurs within 3–4 weeks, with fecundity peaking in 8–10 weeks. Nothobranchius furzeri shows no signs of telomere shortening, reduced telomerase activity, or replicative senescence with age, despite its short lifespan.
As host plant quality begins to deteriorate in late August and early September, soybean aphids take on a paler color and experience decreased growth and reproductive rates. High densities of soybean aphids during these late plant stages have less of a significant negative impact on soybean yield. During this period of declining temperatures and decreasing rainfall, soybean plants undergo senescence gradually from bottom to top, causing an upward movement of soybean aphids to higher plant tissue. After going through approximately 15 generations on soybean, soybean aphids begin to transition back to their primary host, buckthorn.
Greco-Roman texts were preserved, copied and extended although new texts always emphasised the medicinal aspects of plants. Kurdish biologist Ābu Ḥanīfah Āḥmad ibn Dawūd Dīnawarī (828–896 AD) is known as the founder of Arabic botany; his Kitâb al-nabât ('Book of Plants') describes 637 species, discussing plant development from germination to senescence and including details of flowers and fruits. The Mutazilite philosopher and physician Ibn Sina (Avicenna) (c. 980–1037 AD) was another influential figure, his The Canon of Medicine being a landmark in the history of medicine treasured until the Enlightenment.
Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component that serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells, resulting in progressive shortening of telomeres. Studies in mice suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks.
Here, telomere act as a barrier against cells from dividing abnormally, hence providing a stable environment for body functions. The withdrawal process also prevents diseased cells, or cells with mutated or damaged DNA, from continuing to divide and increasing the percentage of abnormal cells inside the body. It can further allow these cells to stop their functions and differentiations to undergo a programmed cell death process called apoptosis. Furthermore, the withdrawal process could allow cells to encounter further parts of their cell life, namely senescence and natural apoptosis.
The cytoplasmic distension is a direct result of the G2/M cell cycle arrest. The cell enlarges in preparation for mitosis, but cannot divide to restore its normal size. Aside from classical apoptosis, signs of cellular senescence has also been observed in normal and cancer cell lines (fibroblasts, HeLa and U2-OS) after CDT intoxication In lymphocytes, cell death occurs quickly and is not preceded by significant cytoplasmic distension. The ability of these toxins to effect lymphocytes differently may be advantageous to the bacteria that utilize these toxins, but the mechanism behind this phenomenon is not yet well understood.
In addition to testing drug candidates that exploit cancer cell's dependence on telomerase, Geron is researching the possible applications of activating the enzyme in normal cells to delay cellular senescence. The company is in the early stages of developing a telomerase based treatment for HIV called TAT0002, which is the saponin cycloastragenol in Chinese herb Astragalus propinquus. Geron has granted a license to Telomerase Activation Sciences to sell TA-65, the telomerase activator agent also derived from astragalus. In October 2010 Intertek/AAC Labs, an ISO 17025 internationally recognized lab, found the largest component of TA-65 to be cycloastragenol.
Ryu SB, Karlsson BH, Ozgen M, Palta JP, Proc Natl, Acad Sci. 94(1997), 12717-12721 More recently, it is reported that LPE can also accelerate color development and promote shelf life of cranberries,Ozgen M, Palta JP, ISHS Acta Horticulturae 628: XXVI International Horticultural Congress and increase fruit qualities of Thompson seedless grapes, in such as soluble solids content (SSC), titratable acidity (TA), firmness, and size.Hong J-H, Hwang SK, Chung G-H, Cowan AK, J Appl Hortic. 9(2007) 112-114 Along with these results show that LPE can accelerate ripening of fruit and also, have potential to protect senescence.
Animal corpses, like this African buffalo, are recycled by the ecosystem, providing energy and nutrients for living creatures Death is the permanent termination of all vital functions or life processes in an organism or cell. It can occur as a result of an accident, medical conditions, biological interaction, malnutrition, poisoning, senescence, or suicide. After death, the remains of an organism re-enter the biogeochemical cycle. Organisms may be consumed by a predator or a scavenger and leftover organic material may then be further decomposed by detritivores, organisms that recycle detritus, returning it to the environment for reuse in the food chain.
Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc70 or Hsp73 is a heat shock protein that in humans is encoded by the HSPA8 gene on chromosome 11. As a member of the heat shock protein 70 family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins. Its functions contribute to biological processes including signal transduction, apoptosis, autophagy, protein homeostasis, and cell growth and differentiation. It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence, and aging.
The DCLRE1B/SNM1B/Apollo protein is a repair exonuclease that digests double-stranded and single-stranded DNA with a 5’ to 3’ directionality. Using an SNM1B/Apollo knockout mouse model, evidence was obtained that SNM1B/Apollo protein is required to protect telomeres against illegitimate non-homologous end joining that can result in genomic instabilityy and consequently in multi-organ developmental failure. In a human patient with Hoyeraal-Hreidarsson syndrome, a dominant negative mutation in the SNM1B/Apollo gene was discovered. This mutation hampered the proper replication of telomeres, leading to major telomeric dysfunction and cellular senescence.
Telomeres are DNA tandem repeats at the end of chromosomes that shorten during each cycle of cell division. Recently, the role of telomeres in cellular senescence has aroused general interest, especially with a view to the possible genetically adverse effects of cloning. The successive shortening of the chromosomal telomeres with each cell cycle is also believed to limit the number of divisions of the cell, contributing to aging. After sufficient shortening, proteins responsible for maintaining telomere structure, such as TRF2, are displaced, resulting in the telomere being recognized as a site of a double-strand break.
Regarding downstream factors, the Tnmd knockout mouse model suggested correlation to collagen I based on the observed abnormal collagen fibrillogenesis resulting in pathologically thicker fibres. The lower cellular density and proliferation in the mutant tendons, as well as the reduced self-renewal and earlier senescence of Tnmd-deficient tendon stem/progenitor cells was coupled with downregulation of the proliferative marker Cyclin D1 and upregulation of the senescent marker p53. A study analysing ruptures of human chordae tendineae cordis revealed loss of Tnmd expression in the affected area coupled with upregulation of VEGF-A and MMP1, 2 and 13.
Tnmd exerts a positive effect on tendon-derived stem/progenitor cells by supporting self- renewal and preventing senescence, actions in which the C-terminal cysteine- rich domain alone is sufficient. The first studies on Tnmd expression during tendon healing suggested a time-dependent role, which needs to be further elucidated. \- In periodontal ligaments mediating the teeth connection to the jaw bones, Tnmd contributes to proper fibroblast adhesion. \- In tendinous structures chordae tendineae cordis, which connect papillary muscle to the atrioventricular valves in the heart, local absence of Tnmd leads to enhanced angiogenesis, VEGF-A production and MMPs activation.
The elderly often suffer from progressive muscle weakness and regenerative failure owing in part to elevated activity of the p38α and p38β mitogen-activated kinase pathway in senescent skeletal muscle stem cells. Subjecting such stem cells to transient inhibition of p38α and p38β in conjunction with culture on soft hydrogel substrates rapidly expands and rejuvenates them that result in the return of their strength. In geriatric mice, resting satellite cells lose reversible quiescence by switching to an irreversible pre-senescence state, caused by derepression of p16INK4a (also called Cdkn2a). On injury, these cells fail to activate and expand, even in a youthful environment.
Although the role of KDM2 in eukaryotic developmental differentiation is still largely a mystery, both KDM2A and KDM2B have been shown to play roles in tumor growth and suppression. KDM2B has been shown to be over-expressed in human lymphomas and adenocarcinomas; prostate cancers and glioblastomas, however, show reduced expression of both KDM2A and KDM2B. Additionally, KDM2B has been shown to prevent senescence in some cells through ectopic expression further indicating its potential as an oncogene. ;KDM3:The KDM3 family includes KDM3A, KDM3B and JMJD1C. KDM3A (also referred to as JHDM2A/JMJD1A/TSGA) can act on mono- and dimethylated H3K9.
Another adaptation to life on discarded antlers is an astonishing degree of site fidelity: males spend their entire lives competing on the same antler (only leaving to spend the night in nearby vegetation), making it possible to mark flies individually and obtain longitudinal field data on these tiny insects. This unique ecology made it possible to document senescence in wild insects for the first time. The waltzing fly, Prochyliza xanthostoma, occurs in North America. It is one of the carrion-feeding piophilids and is remarkable for its sexual dimorphism and its patterns of behavioural adaptation and associated morphological adaptations.
Upon senescence, plant residues, animals and microorganisms enter the dead organic matter pool and become a source of nutrients and energy for other organisms. Extracellular enzymes target macromolecules such as carbohydrates (cellulases), lignin (oxidases), organic phosphates (phosphatases), amino sugar polymers (chitinases) and proteins (proteases) and break them down into soluble sugars that are subsequently transported into cells to support heterotrophic metabolism. Biopolymers are structurally complex and require the combined actions of a community of diverse microorganisms and their secreted exoenzymes to depolymerize the polysaccharides into easily assimilable monomers. These microbial communities are ubiquitous in nature, inhabiting both terrestrial and aquatic ecosystems.
An often cited reason for the dependence of larvae, especially 2nd-brood larvae, on shaded habitat is the possibility of early senescence of wild lupine in open areas resulting in a lack of larval food. Shade-grown wild lupine being more nutritious, possibly due to nitrogen content limiting photosynthesis to a greater extent in open areas, was one of several explanations. The size of wild lupine has been positively associated with Karner blue butterfly larval length and amount of feeding damage. In addition, there may be shade-related effects on Karner blue butterflies that are related to the density of wild lupine.
Emerald Ash Borer, United States Department of Agriculture, National Forest Service Forest Service and Michigan State University An infested tree can be recognized by premature fall color and leaf senescence observed on affected branches between August and last week of September. Before the EAB was officially identified, such dieback symptoms were thought to have been caused by a vascular disease classified as ash yellows. It was assumed damage was caused by the EAB taking advantage of weakened trees. Other recognizable signs regularly observed have been upper crown dieback, epicormic shoots or sprouts, bark lesions, frass filled larval galleries, and deformed exit holes.
This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper- dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family.
Highly elevated cortisol levels mediate the post-spawning death of semelparous Oncorhynchus Pacific salmon by causing tissue degeneration, suppressing the immune system, and impairing various homeostatic mechanisms. After swimming for such a long distance, salmon expend all of their energy on reproduction. One of the key factors in salmon rapid senescence is that these fish do not feed during reproduction so body weight is extremely reduced. In addition to physiological degradation, pacific salmon become more lethargic as mating goes on, which makes some individuals more susceptible to predation because they have less energy to avoid predators.
Geneticists studying these premature-aging syndromes propose that caretaker genes that determine cell fate also play a significant role in aging. Similarly, gatekeeper genes have been identified as having a role in aging disorders that exhibit mutations in such genes without an increased susceptibility to cancer. Experiments with mice that have increased gatekeeper function in the p53 gene show reduced cancer incidence (due to the protective activities of products encoded by p53) but a faster rate of aging. Cellular senescence, also encoded by a gatekeeper gene, is arrest of the cell cycle in the G1 phase.
In cells that lack telomerase expression, it is well-established that most cells instead maintain the ends of their telomeres through the recombination-based Alternative Lengthening of Telomeres (ALT) pathway. It is proposed that TERRA may work to delay the onset of cellular senescence in these cells and instead promote mechanisms of homologous recombination, thereby driving the ALT phenotype as an alternative means of maintaining telomere ends.Ng L. J., Cropley J. E., Pickett H. A., Reddel R. R., Suter C. M. (2009). Telomerase activity is associated with an increase in DNA methylation at the proximal subtelomere and a reduction in telomeric transcription.
Olshansky has been a vocal supporter of scientific attempts to increase the human healthspan. He is an advocate for prolonging the healthy life-span compared to increasing the overall length of life as such. In an interview he advocated for further study of calorie restriction, genetic study of humans centenarians, and for further study on life extension and senescence. He is co-author with Bruce A Carnes of The Quest for Immortality: Science at the Frontiers of Aging (Norton, 2001) and with Jim Kirkland and George Martin he co-edited "Aging: The Longevity Dividend", published in 2015.
In one such pathway, caspase-independent apoptosis, the E3 ligase C-terminal of Hsc-70 interacting protein (CHIP), a regulator of EndoG expression, functions as a protective mechanism against oxidative stress. Under normal conditions, EndoG remains bound to Hsp70 and CHIP; however, when undergoing oxidative stress, EndoG dissociates from Hsp70 and CHIP and translocates to the nucleus, where it degrades DNA to effect apoptosis. Therefore, maintaining low levels of EndoG could prevent cell death caused by stress conditions. In epithelial cells, the nuclear localization and proapoptotic function of EndoG leads it to play a role in cell senescence.
Previous studies reported greater efficacy of anticancer drugs when used in conjunction with high EndoG levels. Thus, regulators of EndoG, such as CHIP, could serve as therapeutic targets for oxidative stress-induced cell death in cancer and aging. Through its association with cell senescence in epithelial cells, EndoG may also contribute to age-related vascular diseases such as arteriosclerosis. Similarly, myonuclear localization of EndoG is correlated with atrophied aging skeletal muscle, leading to increased apoptotic signaling and muscle mass loss. EndoG has also been implicated in Parkinson’s disease (PD), as it induces DNA fragmentation in neurons when translocated from the mitochondria to nuclei.
Unripe berries may be seen from late June up until the third week of September. Ripe berries are present from the beginning of September to mid-October, nearly all being ripe by the end of September.Senescence is observable between early/mid-September and late October: the first signs of foliar senescence have become noticeable by mid- September and by mid-October practically all plants are reduced to stands of leafless stems, the non -flowering basal rosettes being the last to lose their leaves. The last vestiges of aerial growth disappear shortly after the first rains or heavy falls of snow.
To provide required nutrients, embryonic stem cells of chickens may have been re-added to the culture daily. This would have easily allowed the cultivation of new, fresh cells in the culture, so there was not an infinite reproduction of the original cells. It has been speculated that Carrel knew about this error, but he never admitted it. Also, it has been theorized that the cells Carrel used were young enough to contain pluripotent stem cells, which, if supplied with a supporting telomerase-activation nutrient, would have been capable of staving off replicative senescence, or even possibly reversing it.
Methyl CpG-binding protein 2 (MeCP2) is a transcriptional regulator that must be phosphorylated before releasing from the BDNF promoter, allowing transcription. Rett syndrome is underlain by mutations in the MeCP2 gene despite no large-scale changes in expression of MeCP2 being found in microarray analyses. BDNF is downregulated in the MECP2 mutant resulting in Rett syndrome, as well as the increase of early neural senescence and accumulation of damaged DNA. In the Överkalix study, paternal (but not maternal) grandsonsA person's paternal grandson is the son of a son of that person; a maternal grandson is the son of a daughter.
The hormonal control of growth, differentiation and development in plants was Osborne's lifelong interest. She is particularly known for her work establishing that the gas ethylene is a natural plant hormone, rather than a by-product or pollutant, and for demonstrating that ethylene, rather than abscisic acid, is the major regulator of senescence (ageing) and abscission (shedding of parts such as leaves).Society for Experimental Biology: Jackson M. Daphne J Osborne (1925–2006). SEB Bulletin (October 2006) (accessed 7 January 2009) She conducted extensive research into interactions between ethylene and auxin (another key plant hormone) in controlling numerous aspects of plant development.
During this first stage, the terrain is steeper and more irregular. Over time, the currents can carve wider valleys ("maturity") and then start to wind, towering hills only ("senescence"). Finally, everything comes to what is a plain flat plain at the lowest elevation possible (called "baseline") This plain was called by Davis' "peneplain" meaning "almost plain" Then river rejuvenation occurs and there is another mountain lift and the cycle continues. Although Davis's theory is not entirely accurate, it was absolutely revolutionary and unique in its time and helped to modernize and create a geography subfield of geomorphology.
Preterm births (births taking place before 37 weeks) can be the result of a number of causes such as, in utero infection, inflammation, vascular disease and uterine overdistension. The risk of spontaneous preterm birth is increased by a previous preterm birth, black race, periodontal diseases and low maternal body-mass index. Key indicators of preterm birth are short cervical length and a raised cervical- vaginal fetal fibronectin concentration. Pathophysiology of the fetal membranes, such as microfractures, senescence of cells in the fetal membrane and inflammation can lead to an increased chance of preterm premature rupture of the fetal membranes (pPROM).
PPRHs could be used as gene silencing tools acting by different mechanisms than triplex forming oligonucleotides (TFOs), antisense oligonucleotides or siRNAs. Upon binding to their targets, PPRHs can decrease the mRNA and protein levels of the selected genes. Their action has been demonstrated in vitro for a number of genes involved in metabolism (DHFR), proliferation (mTOR), DNA topology (TOP1), lifespan and senescence (telomerase), apoptosis (survivin, BCL2), transcription factors (MYC), proto-oncogenes (MDM2), replication stress (WEE1, CHK1) and Thymidilate synthase (TYMS) as part of a cancer gene therapy strategy. Their preclinical proof of principle has been proven in vivo using the antiapoptotic survivin gene.
At first, this was thought to increase RLS by up-regulating the sir2 enzyme, however it was later discovered that this effect is independent of sir2. Over-expression of the genes sir2 and fob1 has been shown to increase RLS by preventing the accumulation of extrachromosomal rDNA circles, which are thought to be one of the causes of senescence in yeast. The effects of dietary restriction may be the result of a decreased signaling in the TOR cellular pathway. This pathway modulates the cell's response to nutrients, and mutations that decrease TOR activity were found to increase CLS and RLS.
Giant Pacific octopuses are semelparous; they breed once before death. After reproduction, they enter a stage called senescence, which involves obvious changes in behavior and appearance, including a reduced appetite, retraction of skin around the eyes giving them a more pronounced appearance, increased activity in uncoordinated patterns, and white lesions all over the body. While the duration of this stage is variable, it typically lasts about one to two months. Death is typically attributed to starvation, as the females stop hunting and instead protect their eggs; males often spend more time in the open, making them more likely to be preyed upon.
The 2017 95% prediction interval of 2090 average life expectancy rises as high as +6 (106, in Century Representation Form) by 2090, with dramatic, ongoing, layered consequences on world population and demography should that happen. The prediction interval is extremely wide, and the United Nations can not be certain. Organizations like the Methuselah Foundation are working toward an end to senescence and practically unlimited human lifespan. If successful, the demographic implications for human population will be greater in effective multiplier terms than any experienced in the last five centuries if maximum lifespan or the birthrate remain unlimited by law.
Fisetin, like some other flavonoids, has been found in lab studies to be a topoisomerase inhibitor, which may turn out to be a carcinogenic activity or an anti-cancer activity - further research is needed. Fisetin has been shown to be an effective senolytic agent in wild-type mice, with effects of increased lifespan, reduced senescence markers in tissues, and reduced age-related pathologies. Studies of cell cultures of senescent human umbilical vein endothelial cells have shown that fisetin induces apoptosis by inhibition of the anti-apoptotic protein Bcl-xL. Fisetin has roughly twice the senolytic potency as quercetin.
In skin wound healing, CYR61 is highly expressed in the granulation tissue by myofibroblasts, which proliferate and rapidly synthesize ECM to maintain tissue integrity and to promote regeneration of parenchymal cells. However, excessive matrix deposition can lead to fibrosis, scarring, and loss of tissue function. In skin wounds, CYR61 accumulates in the granulation tissue as myofibroblasts proliferate, and eventually reaches a sufficiently high level to drive the myofibroblasts themselves into senescence, whereupon these cells cease to proliferate and express matrix-degrading enzymes. Thus, CYR61 limits synthesis and deposition of ECM by myofibroblasts, reducing the risk of fibrosis during wound healing.
From Aguamilpa, the river descends to the coastal lowlands, passing by Santiago Ixcuintla and empties into the Pacific Ocean, northwest of San Blas, in Nayarit. The river is viewed by some sources as a continuation of the Lerma River, which flows into Lake Chapala. Mexico possesses a small percentage of the world's freshwater reserve, 0.1%. According to an article named Water use (and abuse) and its effects on the crater-lakes of Valle de Santiago, Mexico “most Mexican lakes are in an advanced state of desiccation or senescence, with volumes and surface area greatly reduced because of human activities”.
Memory capabilities decline with age, evident in human degenerative diseases such as Alzheimer's disease, which is accompanied by an accumulation of oxidative damage. Current studies demonstrate that the accumulation of ROS can decrease an organism's fitness because oxidative damage is a contributor to senescence. In particular, the accumulation of oxidative damage may lead to cognitive dysfunction, as demonstrated in a study in which old rats were given mitochondrial metabolites and then given cognitive tests. Results showed that the rats performed better after receiving the metabolites, suggesting that the metabolites reduced oxidative damage and improved mitochondrial function.
Several studies have concluded that ADT has demonstrated benefit in patients with metastatic disease, and as an adjunct to radiation therapy in patients with locally advanced disease, as well as those with unfavorable intermediate-risk or high- risk localized disease. However, in patients with low-risk prostate cancer, ADT has demonstrated no survival advantage, and significant harm, such as impotence, diabetes and bone loss. The therapy can also eliminate cancer cells by inducing androgen deprivation-induced senescence. Lowering androgen levels or stopping them from getting into prostate cancer cells often makes prostate cancer shrink or grow more slowly for a time.
The transfer of nitrogen and carbon as discussed above readily occurs through live pelotons, but it has been observed by Kuga 2014 and Rasumussen 2009 that large amount of carbon and nitrogen may also be taken up by the plant during the senescence and digestion of fungal pelotons. This process is called mycophagy. Lysis of pelotons begins between 30 and 40 hours after contact and initial peloton formation within the majority of observed orchid plants. As mentioned above as pelotons are formed they are covered by a plant derived membrane, which eventually takes on the properties of endoplasmic reticulum surrounded by Golgi apparatuses.
This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family.
Turesson's ideas and findings have had a lasting effect on evolutionary biology of plants. At the main campus of the Swedish University of Agricultural Sciences in Ultuna, one may still see a long row of birch trees of provenances ranging from Scania to Lappland, planted by Turesson. Spectacularly, bud burst in spring starts in the end of the southern provenances and proceeds 'northwards', while autumn leaf colouring and senescence starts in the northern provenances and proceeds 'southwards'. Thus, Turesson continues to remind SLU students that phenology has a genetic basis and that local adaption may be revealed in common garden experiments.
If the rate of DNA damage exceeds the capacity of the cell to repair it, the accumulation of errors can overwhelm the cell and result in early senescence, apoptosis, or cancer. Inherited diseases associated with faulty DNA repair functioning result in premature aging, increased sensitivity to carcinogens, and correspondingly increased cancer risk (see below). On the other hand, organisms with enhanced DNA repair systems, such as Deinococcus radiodurans, the most radiation- resistant known organism, exhibit remarkable resistance to the double-strand break-inducing effects of radioactivity, likely due to enhanced efficiency of DNA repair and especially NHEJ.
Relationship between fully differentiated "old" cells, pluripotent stem cells produced through classical cloning, and "young" cells produced by partial cloning. In the field of cell biology, the method of partial cloning (PCL) converts a fully differentiated old somatic cell into a partially reprogrammed young cell that retains all the specialised functions of the differentiated old cell but is simply younger. The method of PCL reverses characteristics associated with old cells. For example, old, senescent, cells rejuvenated by PCL are free of highly condensed senescence-associated heterochromatin foci (SAHF) and re-acquire the proliferation potential of young cells.
Another study in a mouse model shows that stem cells do age and their aging can lead to heart failure. Findings of the study indicate that diabetes leads to premature myocyte senescence and death and together they result in the development of cardiomyopathy due to decreased muscle mass. Recent work has suggested that, although adult tissue stem cells may the key cell type in the aging process, they may contribute via reducing their differentiation rates, rather than via becoming exhausted. Under this model, when stem cells divide but do not differentiate, they produce an excess of daughter stem cells.
In turn, it is well known from Williams' theory of the evolution of senescence that strong selection for enhanced early function readily accommodates, through antagonistic pleiotropy, deleterious later occurring effects, thus potentially accounting for the especially early demise of the thymus. The disposable soma hypothesis and life history hypothesis say similarly that tradeoffs are involved in thymic involution. Since the immune system must compete with other bodily systems, notably reproduction, for limited physiological resources, the body must invest in the immune system differentially at different stages of life. There is high immunological investment in youth since immunological memory is low.
Linopirdine is a putative cognition-enhancing drug with a novel mechanism of action. Linopirdine blocks the KCNQ2\3 heteromer M current with an IC50 of 2.4 micromolar disinhibiting acetylcholine release, and increasing hippocampal CA3-schaffer collateral mediated glutamate release onto CA1 pyramidal neurons. In a murine model linopirdine is able to nearly completely reverse the senescence-related decline in cortical c-FOS, an effect which is blocked by atropine and MK-801, suggesting Linopirdine can compensate for the age related decline in acetylcholine release. Linopirdine also blocks homomeric KCNQ1 and KCNQ4 voltage gated potassium channels which contribute to vascular tone with substantially less selectivity than KCNQ2/3.
Interestingly, even after oncogenic activation of a tissue, several researchers have identified a senescent phenotype. Researchers have identified a senescent phenotype in benign lesions of the skin carrying oncogenic mutations in neurofibroma patients with a defect that specifically causes an increase in Ras. This finding has been highly reproducible in benign prostate lesions, in melanocytic lesions of UV-irradiated HGF/SF-transgenic mice, in lymphocytes and in the mammary gland from N-Ras transgenic mice, and in hyperplasias of the pituitary gland of mice with deregulated E2F activity. The key to these findings is that genetic manipulations that abrogated the senescence response led to full-blown malignancy in those carcinomas.
Presence of un-phosphorylated Rb drives cell cycle exit and maintains senescence. At the end of mitosis, PP1 dephosphorylates hyper- phosphorylated Rb directly to its un-phosphorylated state. Furthermore, when cycling C2C12 myoblast cells differentiated (by being placed into a differentiation medium), only un-phosphorylated Rb was present. Additionally, these cells had a markedly decreased growth rate and concentration of DNA replication factors (suggesting G0 arrest). This function of un-phosphorylated Rb gives rise to a hypothesis for the lack of cell cycle control in cancerous cells: Deregulation of Cyclin D - Cdk 4/6 phosphorylates un-phosphorylated Rb in senescent cells to mono-phosphorylated Rb, causing them to enter G1.
A tawny owl of around fledgling age in Scotland. Breeding success averages fairly high in this species. A study within oak- hornbeam-birch forest in Hungary on the breeding output of males, 77 males examined from the 1st breeding year until 9 years of age, increase breeding output from 2 to 4 years of age thence peaking at 5–6 in age. However, at older than this the male breeding output begins to decline, possibly due to senescence, perhaps since males may be unable to continue withhold high- quality territories from competition. The 5 to 9-year-old males were flexible to prey variations in ways younger males were not.
Elongation of a corn silk strand stops soon after a grain of pollen is captured, or due to senescence of the silk 10 days after its emergence. If an ovule is successfully fertilized, the corn silk will detach from it two or three days later. Otherwise, the silk will remain attached indefinitely, and fertilization remains possible (with decreasing chances of success) for 10 days after silk emergence. For this reason, it is possible to sample developing ears of corn from a field, husking them gently with a sharp knife, then shaking them to assess the progress of pollination based on how much of the corn silk falls away.
The first and still most widely used immortal cell line is HeLa, developed from cells taken from the malignant cervical tumor of Henrietta Lacks without her consent in 1951. Prior to the 1961 work of Leonard Hayflick, there was the erroneous belief fostered by Alexis Carrel that all normal somatic cells are immortal. By preventing cells from reaching senescence one can achieve biological immortality; telomeres, a "cap" at the end of DNA, are thought to be the cause of cell aging. Every time a cell divides the telomere becomes a bit shorter; when it is finally worn down, the cell is unable to split and dies.
The advantages of subtelomeres have been studied in different species such as Plasmodium_falciparum, Drosophila melanogaster, Saccharomyces cerevisiae, since they have similar genetic elements to humans, not accounting for length and sequence. Subtelomeres might have the same role in plants since the same advantage have been found in a common bean plant known as Phaseolus vulgaris. Different varieties of subtelomeres are frequently rearranging during meiotic and mitotic recombination, indicating that subtelomeres are frequently shuffling, which causes new and rapid genetic changes in chromosomes. In Saccharomyces cerevisiae, 15kb region of chromosome 7L in subtelomeres maintained cell viability in the removal of telomerase, while the removal of the last 15kb increased chromosome senescence.
Reduced DNA repair causes increased impairment of transcription and progressive loss of cell and tissue function. However, these harmful effects of DNA damage are cumulative and most severe in chronologically older individuals whose numbers diminish with time (by causes of death that can be independent of senescence). As a consequence, the beneficial effects of the genetic elements that control the reduction of DNA repair early in life would predominate. Thus regulatory genetic elements that reduce expression of DNA repair genes in post-mitotic cells appear to be important examples of the postulated pleiotropic "genes" that are beneficial in youth but deleterious at an older age.
For the majority of isolated primary cells, they undergo the process of senescence and stop dividing after a certain number of population doublings while generally retaining their viability (described as the Hayflick limit). A bottle of DMEM cell culture medium Aside from temperature and gas mixture, the most commonly varied factor in culture systems is the cell growth medium. Recipes for growth media can vary in pH, glucose concentration, growth factors, and the presence of other nutrients. The growth factors used to supplement media are often derived from the serum of animal blood, such as fetal bovine serum (FBS), bovine calf serum, equine serum, and porcine serum.
Ending Aging: The Rejuvenation Breakthroughs that Could Reverse Human Aging in Our Lifetime is a 2007 book written by Aubrey de Grey, a biomedical gerontologist, with his research assistant Michael Rae. Ending Aging describes de Grey's proposal for eliminating aging as a cause of debilitation and death in humans, and restoring the body to an indefinitely youthful state, a project plan that he calls the "Strategies for Engineered Negligible Senescence", or "SENS". De Grey argues that defeating aging is feasible, possibly within a few decades, and he outlines steps that can be taken to hasten the development of regenerative medicine treatments that will save lives.
Older man from Faridabad, Haryana, India The mutation accumulation theory of ageing was first proposed by Peter Medawar in 1952 as an evolutionary explanation for biological ageing and the associated decline in fitness that accompanies it. Medawar used the term 'senescence' to refer to this process. The theory explains that, in the case where harmful mutations are only expressed later in life, when reproduction has ceased and future survival is increasingly unlikely, then these mutations are likely to be unknowingly passed on to future generations. In this situation the force of natural selection will be weak, and so insufficient to consistently eliminate these mutations.
The implication that flight, and therefore lower predation, increases lifespan is further born out by the fact that bats live on average 3 times longer than similarly sized mammals with comparable metabolic rates. Providing further evidence, insect populations are known to experience very high rates of extrinsic mortality, and as such would be expected to experience rapid senescence and short life spans. The exception to this rule, however, is found in the longevity of eusocial insect queens. As expected when applying the mutation accumulation theory, established queens are at almost no risk of predation or other forms of extrinsic mortality, and consequently age far more slowly than others of their species.
EMBO J. 15, 5690–5700 The parsley WRKY proteins also provided the first evidence that WRKY transcription factors play roles in regulating plant responses to pathogens. Numerous papers have now shown this to be a major function of WRKY transcription factors. Since these initial publications, it has become clear that the WRKY family is among the ten largest families of transcription factors in higher plants and that these transcription factors play key roles in regulating a number of plant processes including the responses to biotic and abiotic stresses, germination, senescence, and some developmental processes.Eulgem, T. and Somssich, I.E. (2007) Networks of WRKY transcription factors in defense signaling. Curr. Opin.
Structurally, hepaCAM is a glycoprotein containing an extracellular domain with 2 Ig-like loops, a transmembrane region and a cytoplasmic domain. Matched to chromosome 11q24, gene HEPACAM is ubiquitously expressed in normal human tissues, with particularly high expression levels in the central nervous system (CNS), and is frequently suppressed in a variety of tumour types. Functionally, hepaCAM is involved in cell-extracellular matrix interactions and growth control of cancer cells, and is able to induce differentiation of glioblastoma cells. In cell signaling, hepaCAM directly interacts with F-actin and calveolin 1, and is capable of inducing senescence-like growth arrest via a p53/p21-dependent pathway.
"Bose began by applying delicate instrumentation he had invented in his semiconductor research to deliver electrical stimuli and record electrical responses from various plant parts... He discovered that both living animal and plant tissues exhibited a diminution of sensitivity after continuous stimulation, recovery after rest, a 'staircase' or summation of electrical effects following mechanical stimulation, abolition of current flow after applying poisons and reduced sensitivity at low temperature." He stated from his experiments that an electrical spasm occurs during the end of life for a plant.Biswal, Basanti; Krupinska, Karin; Biswal, Udaya C. (2013). Plastid Development in Leaves During Growth and Senescence. Springer. p. 303.
These studies also provided a paradigm for Jackson's later work on DNA-damage signalling by the ATM serine/threonine kinase and ATR (Ataxia telangiectasia and Rad3 related), and his studies on how these and additional DNA repair factors interact with and influence one another, often in ways regulated by post-translational modifications. Jackson's work has also helped establish how DSB repair is controlled during the cell cycle, at telomeres in response to cell aging/senescence, and within chromatin. In 1997 Jackson founded KuDOS Pharmaceuticals with the aim of translating knowledge of DNA damage response pathways into new treatments for cancer. KuDOS developed small-molecule inhibitors of several DNA damage response enzymes.
Nutlins are cis-imidazoline analogs which inhibit the interaction between mdm2 and tumor suppressor p53, and which were discovered by screening a chemical library by Vassilev et al. Nutlin-1, nutlin-2, and nutlin-3 were all identified in the same screen; however, Nutlin-3 is the compound most commonly used in anti-cancer studies. Nutlin small molecules occupy p53 binding pocket of MDM2 and effectively disrupt the p53–MDM2 interaction that leads to activation of the p53 pathway in p53 wild-type cells. Inhibiting the interaction between mdm2 and p53 stabilizes p53, and is thought to selectively induce a growth-inhibiting state called senescence in cancer cells.
This elevated mortality rate continued throughout adulthood, perhaps due to the high physiological demands of procreation, including stress and injuries received during intraspecific competition for mates and resources, and eventually, the ever- increasing effects of senescence. The higher mortality rate in adults may explain their more common preservation. Very large animals were rare because few individuals survived long enough to attain such sizes. High infant mortality rates, followed by reduced mortality among juveniles and a sudden increase in mortality after sexual maturity, with very few animals reaching maximum size, is a pattern observed in many modern large mammals, including elephants, African buffalo, and rhinoceros.
Murphy's lab at Princeton focuses on identifying transcriptional targets related to longevity, using the roundworm Caenorhabditis elegans as a model. Early in her career, Murphy and her postdoctoral mentor Cynthia Kenyon determined that by deactivating one C. elegans gene, called "daf-2", the worms' life expectancy doubled and they expressed a delayed senescence, showing marked behavioral improvements in long-term memory, working memory, and navigational capabilities as compared to the control. The specific longevity genes she is interested in relate to communication between different types of tissue. Once these genetic pathways in different tissue types are identified, they can be monitored in vitro in C. elegans.
Loss of function mutations of the PML protein, particularly resulting from the fusion of the PML gene with RARα gene in Acute promyelocytic leukemias, is implicated in several tumor suppressing apoptotic pathways, particularly those that rely on p53 as noted above. Thus, the loss of PML function confers a cellular survival and proliferation advantage, impedes cellular senescence through loss of SAHFs, and puts a block on cellular differentiation. Both humans and mice have been found to demonstrate an increased propensity for tumor formation upon loss of PML function. PML disruption occurs in a wide variety of cancer types, and results in more metastatic tumors, and correspondingly poorer prognoses.
Hayflick's discovery later contributed to the determination of the biological roles of telomeres. Hayflick claimed that the finite capacity of normal human cells to replicate was an expression of aging or senescence at the cellular level. During this period of research, Hayflick also discovered that if cells were properly stored in a freezer, cells would remain viable and that an enormous number of cells could be produced from a single starting culture. One of the cell strains that Hayflick isolated, which he named WI-38, was found to be free of contaminating viruses, unlike the primary monkey kidney cells then in use for virus vaccine production.
It will be a round- trip journey, returning to the solar system after five million years, though only a thousand years will elapse on board, due to relativistic time dilation effects. The crew is broken into three factions—the primitives, the virtuals, and a survivalist faction, Superet. Among the factions, the primitives are a eugenics project for Garry Uvarov who hopes to lengthen the lives of humanity without the use of Anti-Senescence (anagathic or life-extension) technology. The Superet faction relies heavily on failing technology and maintains a totalitarian government which refuses to acknowledge the existence of other decks on the ship; the virtuals remain aloof.
CpTI was first approved for use cotton in 1999 and is currently undergoing trials in rice. Less than one percent of GM crops contained other traits, which include providing virus resistance, delaying senescence and altering the plants composition. Adoption by farmers has been rapid, between 1996 and 2013, the total surface area of land cultivated with GM crops increased by a factor of 100.ISAAA 2013 Annual Report Executive Summary, Global Status of Commercialized Biotech/GM Crops: 2013 ISAAA Brief 46-2013, Retrieved 6 August 2014 Geographically though the spread has been uneven, with strong growth in the Americas and parts of Asia and little in Europe and Africa.
Elevated Hsp70 levels in tumor cells may increase malignancy and resistance to therapy by complexing, and hence, stabilizing, oncofetal proteins and products and transporting them into intracellular sites, thereby promoting tumor cell proliferation. As a result, tumor vaccine strategies for Hsp70s have been highly successful in animal models and progressed to clinical trials. Alternatively, overexpression of Hsp70 can mitigate the effects of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease (PD), Huntington’s disease, and spinocerebellar ataxias, and aging and cell senescence, as observed in centenarians subjected to heat shock challenge. HSPA1L may fight against PD by co-regulating the translocation of parkin to damaged mitochondria, thus facilitating their removal.
Though he refused the offer, Baraggan was forced to submit after Aizen easily killed many of his followers and bore a grudge against the Soul Reaper through his entire career as an Espada. As an Espada, Baraggan's representation of death is senescence, the death brought on by age. He has the unique ability to control entropy, weakening and slowing down the bodies of enemies who come near to him as if they had become elderly; thus, he can easily avoid the attacks of his opponents. His touch can make the body parts of his enemies age to the point of becoming immovable and useless.
The disposable soma theory of aging states that organisms age due to an evolutionary trade-off between growth, reproduction, and DNA repair maintenance. Formulated by Thomas Kirkwood, the disposable soma theory explains that an organism only has a limited amount of resources or "soma" that it can allocate to its various cellular processes. Therefore, a greater investment in growth and reproduction would result in reduced investment in DNA repair maintenance, leading to increased cellular damage, shortened telomeres, accumulation of mutations, compromised stem cells, and ultimately, senescence. Although many models, both animal and human, have appeared to support this theory, parts of it are still controversial.
When his career began, the medical profession largely treated aging like a disease, but Cohen argued based on his research that the brain would continue creating new cells at any age so long as it was engaged in new and challenging intellectual activities. His work in a number of studies on aging supported this belief, including a 2002 study which suggested that involvement in the arts late in life led to a lower incidence of illness and injury. According to Dr. Walter Reich, a colleague at George Washington University, "Single-handedly he changed the image of aging from one of senescence to a period of creativity." Cohen was a prolific writer.
IPF is believed to be the result of an aberrant wound healing process including/involving abnormal and excessive deposition of collagen (fibrosis) in the pulmonary interstitium with minimal associated inflammation. Cellular senescence is suspected to be a central contributing cause, a belief which is supported by benefits seen in patients given senolytic therapy. It is hypothesized that the initial or repetitive injury in IPF occurs to the lung cells, called alveolar epithelial cells (AECs, pneumocytes), which line the majority of the alveolar surface. When type I AECs are damaged or lost, it is thought that type II AECs undergo proliferation to cover the exposed basement membranes.
The use of electron microscopy to view the DNA in the mitochondrial matrix helped to verify the actuality of the mitochondrial genome. S. cerevisiae has since become a useful model for aging. It has been shown that as yeast ages, it loses functional mitochondrial DNA, which leads to replicative senescence, or the inability to further replicate. It has been suggested that there is a link between mitochondrial DNA loss and replicative life span (RLS), or the number of times a cell can reproduce before it dies, as it has been found that an increase in RLS is established with the same changes in the genome that enhance the propagation of cells that do not contain mitochondrial DNA.
However, iPSCs were found to be potentially tumorigenic, and, despite advances, were never approved for clinical stage research in the United States. Setbacks such as low replication rates and early senescence have also been encountered when making iPSCs, hindering their use as ESCs replacements. Additionally, it has been determined that the somatic expression of combined transcription factors can directly induce other defined somatic cell fates (transdifferentiation); researchers identified three neural-lineage-specific transcription factors that could directly convert mouse fibroblasts (skin cells) into fully functional neurons. This result challenges the terminal nature of cellular differentiation and the integrity of lineage commitment; and implies that with the proper tools, all cells are totipotent and may form all kinds of tissue.
It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells. Hsp70 member proteins, including Hsp72, inhibit apoptosis by acting on the caspase-dependent pathway and against apoptosis-inducing agents such as tumor necrosis factor-α (TNFα), staurosporine, and doxorubicin. This role leads to its involvement in many pathological processes, such as oncogenesis, neurodegeneration, and senescence. In particular, overexpression of HSP72 has been linked to the development some cancers, such as hepatocellular carcinoma, gastric cancers, colon cancers, breast cancers, and lung cancers, which led to its use as a prognostic marker for these cancers.
Microsatellites in non-coding regions may not have any specific function, and therefore might not be selected against; this allows them to accumulate mutations unhindered over the generations and gives rise to variability that can be used for DNA fingerprinting and identification purposes. Other microsatellites are located in regulatory flanking or intronic regions of genes, or directly in codons of genes – microsatellite mutations in such cases can lead to phenotypic changes and diseases, notably in triplet expansion diseases such as fragile X syndrome and Huntington's disease. The telomeres at the ends of the chromosomes, thought to be involved in ageing/senescence, consist of repetitive DNA, with the hexanucleotide repeat motif TTAGGG in vertebrates. They are thus classified as minisatellites.
Some critics have cast doubt on the hypothesis because while it addresses how grandparental care could have maintained longer female post-reproductive lifespans, it does not provide an explanation for how it would have evolved in the first place. Some versions of the grandmother hypothesis asserted that it helped explain the longevity of human senescence. However, demographic data has shown that historically rising numbers in older people among the population correlated with lower numbers of younger people. This suggests that at some point grandmothers were not helpful toward the survival of their grandchildren, and does not explain why the first grandmother would forgo her own reproduction to help her offspring and grandchildren.
Two individual nebulae, Bright Heart and Fire Bolt, who embody the human types by which Stapledon was most, namely the saint and the revolutionary. Bright Heart preaches peace, and is martyred; Fire Bolt brings about revolution and changes the social order of the cosmos. With Bright Heart dead, and Fire Bolt crumbling into senescence, the remaining nebulae attempt to bring about universal peace and harmony, but a quarrel over how to do this once again results in war. The history of the nebulae is thus one of tragedy, and as they dissolve into the stars and planets of our own cosmical time, the narrator wonders at the creator who could author such a complex dance of hope and futility.
GeroScience covers topics like chronic low-grade inflammation, cellular senescence, macromolecular damage, oxidative-nitrative stress, maladaptation to cellular and molecular stresses, impaired stem cell function and regeneration, alterations in proteostasis, epigenetic dysregulation, impaired mitochondrial function and cellular metabolism; strategies to improve cardiovascular, neurocognitive, and musculoskeletal health-span; studies using a variety of experimental approaches, including in vivo studies and investigations using isolated tissue preparations and cultured cells; the molecular and cellular mechanisms underlying aging processes; evolutionary biology, biophysics, genetics, genomics, proteomics, molecular biology, cell biology, biochemistry, alternative and complementary medicine (including studies on natural compounds in the context of aging research), endocrinology, immunology, physiology, pharmacology, neuroscience, and veterinary sciences (including veterinary pathology).
Sphingolipids are commonly believed to protect the cell surface against harmful environmental factors by forming a mechanically stable and chemically resistant outer leaflet of the plasma membrane lipid bilayer. Certain complex glycosphingolipids were found to be involved in specific functions, such as cell recognition and signaling. Cell recognition depends mainly on the physical properties of the sphingolipids, whereas signaling involves specific interactions of the glycan structures of glycosphingolipids with similar lipids present on neighboring cells or with proteins. Recently, simple sphingolipid metabolites, such as ceramide and sphingosine-1-phosphate, have been shown to be important mediators in the signaling cascades involved in apoptosis, proliferation, stress responses, necrosis, inflammation, autophagy, senescence, and differentiation.
Greider then completed her postdoctoral work, and also held a faculty position, at the Cold Spring Harbor Laboratory, Long Island, New York. Greider continued to study Tetrahymena telomerase, cloning the gene encoding the RNA component and demonstrating that it provided the template for the TTGGGG telomere repeats (1989) as well as establishing that telomerase is processive (1991). She was also able to reconstitute Tetrahymena telomerase in vitro (1994) and define the mechanisms of template utilization (1995). Greider also worked with Calvin Harley to show that telomere shortening underlies cellular senescence (1990). To further test this idea mouse and human telomerase were characterized (1993) (1995) and the mouse telomerase RNA component was cloned (1995).
Cells damaged using gamma irradiation without drug treatment showed cell cycle arrest and then recovered, while the same cells treated with drug to simulate UV-type p53 dynamics entered senescence and failed to divide. These results led Lahav to investigate whether the schedule of drug administration might affect the response to common types of combination therapy in cancer, in which drugs are given in combination with radiation therapy. She found that if radiation was given shortly after addition of an Mdm2 inhibitor the treatment enhanced the effect of radiation, whereas a longer gap between the two treatments led to resistance. There is growing consensus that dynamics are important for signaling in multiple biological pathways.
After just two years, juveniles were larger than any other predator in the region aside from adult Albertosaurus, and more fleet of foot than most of their prey animals. This resulted in a dramatic decrease in their mortality rate and a corresponding rarity of fossil remains. Mortality rates doubled at age twelve, perhaps the result of the physiological demands of the rapid growth phase, and then doubled again with the onset of sexual maturity between the ages of fourteen and sixteen. This elevated mortality rate continued throughout adulthood, perhaps due to the high physiological demands of procreation, including stress and injuries received during intraspecific competition for mates and resources, and eventually, the ever-increasing effects of senescence.
Flowering in some plants signals senescence while in others plants the production of fruits and seeds causes changes within the plants which lead to death. These changes are induced by chemicals that act as hormones, redirecting the resources of the plants from the roots and leaves to the production of fruits and or seeds. The century plant in the genus Agave, some terrestrial bromeliads of the genus Puya, Tillandsia utriculata, some yuccas, and many bamboos can take 8 to 20 years or in the case of some bamboos even over 100 years to bloom and then die. Hawaiian silverswords and their relatives in the genus Wilkesia may take 10–50 years before flowering.
Thus there is a net increase in cell number as the number of cells that die by apoptosis or senescence remains the same. The cells which are actively undergoing cell cycle are targeted in cancer therapy as the DNA is relatively exposed during cell division and hence susceptible to damage by drugs or radiation. This fact is made use of in cancer treatment; by a process known as debulking, a significant mass of the tumor is removed which pushes a significant number of the remaining tumor cells from G0 to G1 phase (due to increased availability of nutrients, oxygen, growth factors etc.). Radiation or chemotherapy following the debulking procedure kills these cells which have newly entered the cell cycle.
Anti-aging drugs are a potential tool for extending life. Aubrey de Grey, a theoretical gerontologist, has proposed that aging can be reversed by Strategies for Engineered Negligible Senescence. De Grey has established The Methuselah Mouse Prize to award money to researchers who can extend the maximum life span of mice. So far, three Mouse Prizes have been awarded: one for breaking longevity records to Dr. Andrzej Bartke of Southern Illinois University (using GhR knockout mice); one for late-onset rejuvenation strategies to Dr. Stephen Spindler of the University of California (using caloric restriction initiated late in life); and one to Dr. Z. Dave Sharp for his work with the pharmaceutical rapamycin.
IGF-1 activates the insulin receptor at approximately 0.1 times the potency of insulin. Part of this signaling may be via IGF1R/Insulin Receptor heterodimers (the reason for the confusion is that binding studies show that IGF1 binds the insulin receptor 100-fold less well than insulin, yet that does not correlate with the actual potency of IGF1 in vivo at inducing phosphorylation of the insulin receptor, and hypoglycemia). IGF-1 binds and activates its own receptor, IGF-1R, through the cell surface expression of Receptor Tyrosine Kinase's (RTK's) and further signal through multiple intracellular transduction cascades. IGF-1R is the critical role-playing inducer in modulating the metabolic effects of IGF-1 for cellular senescence and survival.
The WI-38 cell line stemmed from earlier work by Hayflick growing human cell cultures. In the early 1960s, Hayflick and his colleague Paul Moorhead at the Wistar Institute in Philadelphia, Pennsylvania discovered that when normal human cells were stored in a freezer, the cells remembered the doubling level at which they were stored and, when reconstituted, began to divide from that level to roughly 50 total doublings (for cells derived from fetal tissue). Hayflick determined that normal cells gradually experience signs of senescence as they divide, first slowing before stopping division altogether. This finding is the basis for the Hayflick limit, which specifies the number of times a normal human cell population will divide before cell division stops.
The steady shortening of telomeres with each replication in somatic (body) cells may have a role in senescence and in the prevention of cancer. This is because the telomeres act as a sort of time-delay "fuse", eventually running out after a certain number of cell divisions and resulting in the eventual loss of vital genetic information from the cell's chromosome with future divisions. Telomere length varies greatly between species, from approximately 300 base pairs in yeast to many kilobases in humans, and usually is composed of arrays of guanine-rich, six- to eight-base-pair-long repeats. Eukaryotic telomeres normally terminate with 3′ single-stranded-DNA overhang, which is essential for telomere maintenance and capping.
It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells. Hsp70 member proteins, including Hsp72, inhibit apoptosis by acting on the caspase-dependent pathway and against apoptosis-inducing agents such as tumor necrosis factor-α (TNFα), staurosporine, and doxorubicin. This role leads to its involvement in many pathological processes, such as oncogenesis, neurodegeneration, and senescence. In particular, overexpression of HSP72 has been linked to the development some cancers, such as hepatocellular carcinoma, gastric cancers, colon cancers, breast cancers, and lung cancers, which led to its use as a prognostic marker for these cancers.
Windthrow is common in all forested parts of the world that experience storms or high wind speeds. The risk of windthrow to a tree is related to the tree's size (height and diameter), the 'sail area' presented by its crown, the anchorage provided by its roots, its exposure to the wind, and the local wind climate. A common way of quantifying the risk of windthrow to a forest area is to model the probability or 'return time' of a wind speed that would damage those trees at that location. Tree senescence can also be a factor, where multiple factors contributing to the declining health of a tree reduce its anchorage and therefore increase its susceptibility to windthrow.
It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells. Hsp70 member proteins, including Hsp72, inhibit apoptosis by acting on the caspase-dependent pathway and against apoptosis- inducing agents such as tumor necrosis factor-α (TNFα), staurosporine, and doxorubicin. This role leads to its involvement in many pathological processes, such as oncogenesis, neurodegeneration, and senescence. In particular, overexpression of HSP72 has been linked to the development some cancers, such as hepatocellular carcinoma, gastric cancers, colon cancers, breast cancers, and lung cancers, which led to its use as a prognostic marker for these cancers.
In early 1992, Villeponteau was recruited as the first senior scientist at Geron Corporation with the goal of cloning the human telomerase genes. Telomerase is a two component enzyme (RNA and protein components) that maintains telomere length, which protects the ends of all chromosomes from damage or dysfunction. Since telomere length tends to shorten with age in humans leading to cellular senescence, telomerase was a potential key factor in promoting human aging from human cancer cells that led to the successful cloning of the first human telomerase gene in early 1994.Feng, J., Funk, W.D., Wang, S.S., Weinrich, S.L., Avilion, A.A., Chiu, C.P., Adams, R.R., Chang, E., Allsopp, R.C., Yu, J., et al. (1995).
L. delicatula damages plants directly due to feeding on the sap from the trunk or branches; substantial damage can occur when many insects concurrently feed on the same plant and can present as the senescence of the branches or whole plant. An example of indirect damage is the formation of honeydew, the lanternfly's waste secretions, as sap collects on their trunks as it weeps from the wounds; the accumulation of this sweet sap can attract ants, bees, hornets, and paper wasps. This fosters the growth of molds on the sap as it collects at the base of the plant, which results in a reduction of photosynthetic potential of the plant, even resulting in the death of the plant.
The transgenerational design concept establishes a common ground for those who are committed to integrating age and ability within the consumer population. Its underlying principle is that people, including those who are aged or impaired, have an equal right to live in a unified society. Transgenerational design practice recognizes that human aging is a continuous, dynamic process that starts at birth and ends with death, and that throughout the aging process, people normally experience occurrences of illness, accidents and declines in physical and sensory abilities that impair one's independence and lifestyle. But most injuries, impairments and disabilities typically occur more frequently as one grows older and experiences the effects of senescence (biological aging).
Williams suggested that some genes responsible for increased fitness in the younger, fertile organism contribute to decreased fitness later in life, which may give an evolutionary explanation for senescence. An example is the p53 gene, which suppresses cancer but also suppresses stem cells, which replenish worn-out tissue. Unfortunately, the process of antagonistic pleiotropy may result in an altered evolutionary path with delayed adaptation, in addition to effectively cutting the overall benefit of any alleles by roughly half. However, antagonistic pleiotropy also lends greater evolutionary "staying power" to genes controlling beneficial traits, since an organism with a mutation to those genes would have a decreased chance of successfully reproducing, as multiple traits would be affected, potentially for the worse.
Mutations in the SLC25A46 gene, inherited in an autosomal recessive manner, cause type 6B hereditary motor and sensory neuropathy. Symptoms include early- onset optic atrophy, progressive visual loss, and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease, with variable age at onset and severity. Overexpression of this protein causes mitochondrial fragmentation while knockdown of this protein causes mitochondrial hyperfusion and hyperfilamentous mitochondria due to decreased mitochondrial fission. Loss of this gene also has many other effects: premature cellular senescence, impaired cellular respiration, destabilization of the MICOS (mitochondrial contact site and cristae organizing system) complex, loss of and shortened cristae, altered ER morphology, impaired cell migration, and changes in mitochondrial phospholipid composition.
Congregation of the Regent House on 9 December 2000, Cambridge University Reporter, 13 December 2000. Special regulations available only to Cambridge degree holders (of whatever discipline) permit the submission of "...a significant contribution to scholarship" instead. Though the awardee has not been registered as a PhD student, the degree is not honorary; applicants are evaluated by the usual methods, with examiners appointed and an oral defense of the submitted work. The degree was based on his 1999 book The Mitochondrial Free Radical Theory of Aging, in which de Grey wrote that obviating damage to mitochondrial DNA might by itself extend lifespan significantly, though he said it was more likely that cumulative damage to mitochondria is a significant cause of senescence, but not the single dominant cause.
Certain metal ions found in the body, such as copper and iron, may participate in the process. (In Wilson's disease, a hereditary defect that causes the body to retain copper, some of the symptoms resemble accelerated senescence.) These processes termed oxidative stress are linked to the potential benefits of dietary polyphenol antioxidants, for example in coffee, red wine and tea. Sugars such as glucose and fructose can react with certain amino acids such as lysine and arginine and certain DNA bases such as guanine to produce sugar adducts, in a process called glycation. These adducts can further rearrange to form reactive species, which can then cross-link the structural proteins or DNA to similar biopolymers or other biomolecules such as non-structural proteins.
Elevated Hsp70 levels in tumor cells may increase malignancy and resistance to therapy by complexing, and hence, stabilizing, oncofetal proteins and products and transporting them into intracellular sites, thereby promoting tumor cell proliferation. As a result, tumor vaccine strategies for Hsp70s have been highly successful in animal models and progressed to clinical trials. One treatment, a Hsp72/AFP recombined vaccine, elicited robust protective immunity against AFP-expressing tumors in mice experiments. Therefore, the vaccine holds promise for treating hepatocellular carcinoma. Alternatively, overexpression of Hsp70 can mitigate damage from ischemia-reperfusion in cardiac muscle, as well damage from neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and spinocerebellar ataxias, and aging and cell senescence, as observed in centenarians subjected to heat shock challenge.
His second and third tenures as minister took place in a time of increasing political instability following the assassination of King Carlos I of Portugal by republicans. Teles's parliamentary career and multiple tenures as minister gained a him reputation for significant involvement in party politics generally and the Progressive Party specifically, despite the short duration of many governments during the Portuguese monarchy's twilight. He was a nominee for leader of the Progressive Party during the prolonged senescence of José Luciano de Castro. Portuguese historian Maria Filomena Mónica suggests Teles's relative permanence in government from 1908 through 1909 may be attributed to his desire to elbow out Francisco da Veiga Beirão as the Progressive Party leader, though Teles did not succeed in doing so.
Among the latter, it shows a preference for poppies (Papaver species), burdock (Arctium tomentonum), fat-hen (Chenopodium album), saltbush (Atriplex rosea), chamomile (Matricaria chamomilla), thistles (Cirsium arvense), and docks (Rumex spp.). Two conflicting factors are involved in host preferences, the species and the age of the leaf. Offered spindle and beet leaves on growing plants throughout the year, winged aphids moved from one to the other depending on the active growth state of each and the senescence of each host plant. Thus, in late summer and autumn, the beet leaves were old and unattractive to the aphids in comparison with the leaves of the spindle, whereas in spring, the young unfolding leaves of the beet were more attractive than those of the spindle.
Michael B. Fossel, M.D., Ph.D. (born 1950, Greenwich, Connecticut) is a former professor of clinical medicine at Michigan State University and is the author of several books on aging, who is best known for his views on telomerase therapy as a possible treatment for cellular senescence. Fossel has appeared on many major news programs to discuss aging and has appeared regularly on National Public Radio (NPR). He is also a respected lecturer, author, and the founder and former editor-in-chief of the Journal of Anti-Aging Medicine (now known as Rejuvenation Research). Michael Fossel Prior to earning his M.D. at Stanford Medical School, Fossel earned a joint B.A. (cum laude) and M.A. in psychology at Wesleyan University and a Ph.D. in neurobiology at Stanford University.
Neither vertebrates nor invertebrates consume A. baetica during the earlier stages of its growth cycle; however, during the month of September, when the onset of senescence causes the levels of tropanes in the aerial parts of the plant to fall, it often sustains severe damage from being browsed by the Southeastern Spanish ibex Capra pyrenaica Schinz. ssp. hispanica Schimper. Plants are stripped almost bare of leaves, fruit (both ripe and unripe) and even stem tips. Plants damaged in this way respond by producing small rosettes of leaves – either at ground level or upon the lower third of the flowering stem – which tend to sustain no further browsing damage before winter dormancy, possibly because of alkaloid levels raised as a defense mechanism activated by the check to growth.
This decrease is caused by the increasing likelihood of death due to external pressures such as predation or illness, as well as the internal pressures inherent to organisms that experience senescence. In such cases deleterious mutations which are expressed early on are strongly selected against due to their major impact on the number of offspring produced by that individual. Mutations that present later in life, by contrast, are relatively unaffected by selective pressure, as their carriers have already passed on their genes, assuming they survive long enough for the mutation to be expressed at all. The result, as predicted by Medawar, is that deleterious late-life mutations will accumulate and result in the evolution of ageing as it is known colloquially.
Under most assumptions, the mutation accumulation theory predicts that mortality rates will reach close to 100% shortly after reaching post-reproductive age. Experimental populations of Drosophila Melanogaster, and other organisms, however, exhibit age-specific mortality rates that plateau well before reaching 100%, making mutation accumulation alone an insufficient explanation. It is suggested instead that mutation accumulation is only one factor among many, which together form the cause of ageing. In particular, the mutation accumulation theory, the antagonistic pleiotropy hypothesis and the disposable soma theory of ageing are all believed to contribute in some way to senescence Somatic accumulation of protein truncating variants (PTVs), a form of deleterious or loss of function mutations, may account for only a small fraction of mortality and morbidity acceleration in humans.
Guo, Guo, Xu, Gao, Li, et al. (2014) Evolution and expression analysis of the grape (Vitis vinifera L.) WRKY gene family. Journal of Experimental Botany. 65(6). 1513-1528 In Arabidopsis thaliana, two important WRKY transcription factors are WRKY57 and WRKY70. WRKY57 mediates crosstalk between jasmonate and auxin signaling cascades,Jiang, Liang, Yang and Yu (2014) Arabidopsis WRKY57 Functions as a Node of Convergence for Jasmonic Acid– and Auxin-Mediated Signaling in Jasmonic Acid–Induced Leaf Senescence. The Plant Cell. 26(1). 230-245 whereas WRKY70 moderates signaling between the jasmonate and salicylic acid pathways.Li, Brader and Palva (2004) The WRKY70 Transcription Factor: A Node of Convergence for Jasmonate-Mediated and Salicylate-Mediated Signals in Plant Defense. Plant Cell. 16(2).
The cells of the inner cell mass (embryoblast), which are known as human embryonic stem cells (hESCs), will further differentiate to form four structures: the amnion, the yolk sac, the allantois, and the embryo itself. Human embryonic stem cells are pluripotent, that is, they can differentiate into any of the cell types present in the adult human, and into any of the intermediate progenitor cell types that eventually turn into the adult cell lines. hESCs are also immortal, in that they can divide and grow in number indefinitely, without undergoing either differentiation or cellular aging (cellular senescence). The first differentiation of the hESCs that form the embryo proper, is into three cell types known as the germ layers: the ectoderm, the mesoderm, and the endoderm.
The idea that people develop through adulthood was first explored by G. Stanley Hall, who examined adult development and aging and published the book "Senescence: The Last Half of LIfe", in 1922. Through Hall's research and theorizing on adulthood and old age, he developed the view that aging involved creativity and reviving oneself mentally and emotionally rather than physical and cognitive deterioration. In addition to Hall's work on adult development, Levinson was also influenced by Erik Erikson, who is well known for theory on the stages of psychosocial development. Erikson was one of the pioneers in adult development, as his theory included stages for adulthood, while other theories, such as Jean Piaget's theory of cognitive development, did not extend past adolescence.
However, even though convincing experimental data have identified NF-κB as a critical promoter of tumorigenesis, which creates a solid rationale for the development of antitumor therapy that is based upon suppression of NF-κB activity, caution should be exercised when considering anti-NF-κB activity as a broad therapeutic strategy in cancer treatment as data has also shown that NF-κB activity enhances tumor cell sensitivity to apoptosis and senescence. In addition, it has been shown that canonical NF-κB is a Fas transcription activator and the alternative NF-κB is a Fas transcription repressor. Therefore, NF-κB promotes Fas-mediated apoptosis in cancer cells, and thus inhibition of NF-κB may suppress Fas- mediated apoptosis to impair host immune cell-mediated tumor suppression.
Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Deficits in MMP14 leads to premature aging, short lifespan, and cell senescence in mice, suggesting an important role of MMP14 in extracellular matrix remodeling during aging. Most MMP's are secreted as inactive pro-proteins which are activated when cleaved by extracellular proteinases. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily; each member of this subfamily contains a potential transmembrane domain suggesting that these proteins are tethered to the cell surface rather than secreted.
For more than five decades S. cerevisiae has been studied as a model organism to better understand aging and has contributed to the identification of more mammalian genes affecting aging than any other model organism. Some of the topics studied using yeast are calorie restriction, as well as in genes and cellular pathways involved in senescence. The two most common methods of measuring aging in yeast are Replicative Life Span (RLS), which measures the number of times a cell divides, and Chronological Life Span (CLS), which measures how long a cell can survive in a non-dividing stasis state. Limiting the amount of glucose or amino acids in the growth medium has been shown to increase RLS and CLS in yeast as well as other organisms.
MA/MH technology is achieved by combining proprietary blends of polymers to obtain the desired MVTR and then manipulating the oxygen () and carbon dioxide () transmission rates of the polymer by laser and/or mechanical microperforations. The result is a film which is tailored to provide the optimum modified atmosphere and modified humidity for the produce to be packaged. “Film composition and extent of microperforation are tailored in accordance with the respiratory activity and weight of the produce packaged, anticipated temperature fluctuations during storage and shipment, and expected physiological and pathological responses of the produce to / concentrations and humidity levels inside the package. . . . [MA/MH] packaging allow[s] the formation of a desirable modified atmosphere, retarding ripening and senescence of the produce.
Modifying the atmosphere inside fresh produce packaging to provide lowered levels of and elevated levels of is beneficial for many fresh produce items and “can reduce respiration, decrease ethylene production and action, retard tissue ripening and softening, retard chlorophyll degradation and biosynthesis of carotenoids and anthocyanins, reduce enzymatic browning, alleviate physiological disorders and chilling injury, retard development of decay, and maintain nutritional quality of produce. The effect of decreased and increased on senescence and ripening process are additive and can be synergistic.”Kadar et al., 1989; kader and Saltveit, 2003; Zagory and Kader, 1988 “In vegetative tissues MAP can also reduce leaf regrowth (green onion and leek), stem toughening (asparagus),and leaf sprouting and rooting in root vegetables (parsnip, radishes).
Elevated Hsp70 levels in tumor cells may increase malignancy and resistance to therapy by complexing, and hence, stabilizing, oncofetal proteins and products and transporting them into intracellular sites, thereby promoting tumor cell proliferation. As a result, tumor vaccine strategies for Hsp70s have been highly successful in animal models and progressed to clinical trials. One treatment, a Hsp72/AFP recombined vaccine, elicited robust protective immunity against AFP-expressing tumors in mice experiments. Therefore, the vaccine holds promise for treating hepatocellular carcinoma. Alternatively, overexpression of Hsp70 can mitigate damage from ischemia-reperfusion in cardiac muscle, as well damage from neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and spinocerebellar ataxias, and aging and cell senescence, as observed in centenarians subjected to heat shock challenge.
The functions of AGPs in plant growth and development processes rely heavily on the incredible diversity of their glycan and protein backbone moieties. In particular, it is the AG polysaccharides that are most likely to be involved in development. Most of the biological roles of AGPs have been identified through T-DNA insertional mutants characterization of genes or enzymes involved in AGP glycosylation, primarily in Arabidopsis thaliana. The galt2-6 single mutants revealed some physiological phenotypes under normal growth conditions, including reduced root hair length and density, reduced seed set, reduced adherent seed coat mucilage, and premature senescence. However, galt2galt5 double mutants showed more severe and pleiotropic physiological phenotypes than the single mutants with respect to root hair length and density and seed coat mucilage.
This requirement follows not only from the discussion above but also from in vivo evidence showing the function of this checkpoint in precancerous lesions and its dysfunction in late-stage tumors. Second, to survive after disabling the DNA damage checkpoint, precancerous cells must activate mechanisms to extend their telomeres. As a result of the continued division past the point of normal senescence, the telomeres of these cells become too short to prevent NHEJ(Non Homologous End Joining) and HR(Homologous Recombination) of chromosome ends, causing a state known as crisis. The application of these DSB (double strand breaks)repair mechanisms to chromosome ends leads to genetic instability, and while this instability can promote carcinogenesis, it induces apoptosis if experienced for too long.
De Grey argues that most of the fundamental knowledge needed to develop effective anti-aging medicine already exists, and that the science is ahead of the funding. He works to identify and promote specific technological approaches to the reversal of various aspects of aging, or, as de Grey puts it, "... the set of accumulated side effects from metabolism that eventually kills us."Hang in There: The 25-Year Wait for Immortality interview with LiveScience , his work centered on a detailed plan called Strategies for Engineered Negligible Senescence (SENS), which is aimed at preventing age- related physical and cognitive decline. In March 2009, he cofounded the SENS Research Foundation (named SENS Foundation until early 2013), a non-profit organisation based in California, United States, where he currently serves as Chief Science Officer.
Power, Sex, Suicide: Mitochondria and the Meaning of Life is a 2005 popular science book by Nick Lane of University College London, which argues that mitochondria are central to questions of the evolution of multicellularity, the evolution of sexual reproduction, and to the process of senescence. Amongst the theories advanced in the book, Lane endorses the hydrogen hypothesis for the formation of the eukaryotic cell, whereby mitochondria are the original defining characteristic of the structure. He argues that the event was an exceedingly improbable one and questions the likelihood of it having happened elsewhere in the Universe. He also suggests that the necessity for genetic compatibility between mitochondrial and nuclear DNA lies behind the differentiation of biological genders, ensuring that only one sexual partner contributes mitochondrial DNA to offspring.
From 1940-1960 Gemant was a staff physicist at the Detroit Edison Company. He subsequently held positions as a research associate at Grace Hospital in Detroit, Michigan from 1961-1971 and in Wayne State University's Department of Biochemistry from 1972-1983. He died in February 1983 at the age of 87. Andrew Gemant performed research in the areas of: X-ray fluorescence; pH of aqueous solutions; high voltage physics; dielectrics; colloids; acoustics; viscosity and internal friction of solids; electrets; electrochemistry of oils; radioactive tracers in solutions; high voltage cables; oxidative and photochemical ions in hydrocarbons; ion-exchange resins in hydrocarbons; solubilization of cholesterol; carcinogenesis; enzymic oxidative degradation of protein in senescence; and the reduction by chemical means of the reactivity of DNA (deoxyribonucleic acid) toward hydrogen peroxide in order to mitigate symptoms of aging.
The un-phosphorylated Rb tumour suppressor functions in inducing cell cycle exit and maintaining G0 arrest (senescence). In the last few decades, a model has been widely accepted whereby pRB proteins are inactivated by cyclin D-Cdk4/6-mediated phosphorylation. Rb has 14+ potential phosphorylation sites. Cyclin D-Cdk 4/6 progressively phosphorylates Rb to hyperphosphorylated state, which triggers dissociation of pRB–E2F complexes, thereby inducing G1/S cell cycle gene expression and progression into S phase. However, scientific observations from a recent study show that Rb is present in three types of isoforms: (1) un- phosphorylated Rb in G0 state; (2) mono-phosphorylated Rb, also referred to as “hypo-phosphorylated’ or ‘partially’ phosphorylated Rb in early G1 state; and (3) inactive hyper-phosphorylated Rb in late G1 state.
The longest living person whose dates of birth and death were verified according to the modern norms of Guinness World Records and the Gerontology Research Group was Jeanne Calment (1875–1997), a French woman who reportedly lived to 122. Reduction of infant mortality has accounted for most of the increased average life span longevity, but since the 1960s mortality rates among those over 80 years have decreased by about 1.5% per year. "The progress being made in lengthening lifespans and postponing senescence is entirely due to medical and public-health efforts, rising standards of living, better education, healthier nutrition and more salubrious lifestyles." Animal studies suggest that further lengthening of median human lifespan as well as maximum lifespan could be achieved through "calorie restriction mimetic" drugs or by directly reducing food consumption.
In Showcase #95, the general submitted her to a mind scan to find the secret to immortality, and managed to become young for the briefest moment on his Moon Base until the Doom Patrol got free and started to destroy the base as he began regressing to his former senescence. It turned out the immortality treatment failed because it had been prepared specifically for Arani's physiology. In 2004, DC writer John Byrne restarted the Doom Patrol series and declared that the previous history had never happened, though this revision did not tamper with the history of all its villains, since their history had also been chronicled in various Teen Titans books. Since Infinite Crisis, all Doom Patrol continuity Byrne attempted to wipe out is now largely restored, including that of General Immortus.
The study of its growth rate and the oxygen isotope data showed that it had a highly variable growth at the peak of the Little Ice Age around 1550–1620 and mild climate near its end around 1765–1780 and had recorded the volcanic eruption of Mount Tambora in 1815. One study found that in animals aged 4–192 years, antioxidant enzymes declined rapidly in the first 25 years, which includes the growth and sexual maturity stages, but afterwards remained stable for over 150 years. Though more detailed studies are warranted, it appears this species is a case of negligible senescence. In contrast to the exceptionally long-lived populations in relatively deep, cold parts of its range, more southern populations that experience greater seasonal variations in salinity and temperature are typically far shorter-lived.
Chording mycobacterium tuberculosis culture - luminescent microscope image Focusing his early researches on the molecular basis of homologous genetic recombination and employing RecA paradigm, Muniyappa demonstrated the effects of chromatization of DNA on homologous pairing and strand exchange and his studies are known to have assisted in exploring ways for gene targeting, cell senescence and genome stability. His studies on chromosome synapsis, genetic recombination and telomere dynamics attempted to widen the understanding of cellular recombination and Holliday junction and he is credited with the discovery of a negative regulatory mechanism of homologous recombination. His contributions in deciphering genetic recombination in mycobacterium tuberculosis are also reported to have influenced further researches on the mechanism of genetic exchange and lateral gene transfer. His researches have been published in a number of articles, 136 of which have been listed by ResearchGate, an online article repository.
Extent of the Roman Empire under Augustus. The yellow legend represents the extent of the Republic in 31 BC, the shades of green represent gradually conquered territories under the reign of Augustus, and pink areas on the map represent client states; areas under Roman control shown here were subject to change even during Augustus' reign, especially in Germania. The Julio-Claudians continued to rule Rome after Augustus' death and remained in power until the death of Nero in 68 AD. Augustus' favorites for succeeding him were already dead in his senescence: his nephew Marcellus died in 23 BC, his friend and military commander Agrippa in 12 BC and his grandson Gaius Caesar in 4 AD. Influenced by his wife, Livia Drusilla, Augustus appointed her son from another marriage, Tiberius, as his heir. Suetonius, The Twelve Caesars, Augustus, LXIII.
The ultimate objective of IHEC is to determine how the Epigenome has shaped human populations over generations and in response to the environment. The first phase of IHEC’s operations involves coordinating the production of at least 1,000 reference epigenomes from healthy and diseased human cells, as well as a limited number of model organisms relevant to specific human diseases. The initial focus is on cellular states including stemness, immortality, proliferation, differentiation, senescence, and stress. The reference epigenome for each sample comprises high resolution maps of DNA methylation and key regulatory histone modifications, with corresponding information about the type and expression level of all transcribed genes (protein coding as well as non-coding / small RNAs).Protocols and Standards’ The data produced are made freely available to the research community via the IHEC Data Portal, European Genome-phenome Archive (EGA), and other venues.
Plant Physiology. 143(4). 1789-1801 WRKYs also contribute to determination of seed size and seed coat color in Arabidopsis.Johnson, Kolevski and Smyth (2002) TRANSPARENT TESTA GLABRA2, a Trichome and Seed Coat Development Gene of Arabidopsis, Encodes a WRKY Transcription Factor. The Plant Cell. 14(6). 1359-1375, Luo, Dennis, Berger, Peacock and Chaudhury (2005) MINISEED3 (MINI3), a WRKY family gene, and HAIKU2 (IKU2), a leucine-rich repeat (LRR) KINASE gene, are regulators of seed size in Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America. 102(48). 17531-17536 Furthermore, WRKY transcription factors have been shown to play key roles in regulation of developmentally programmed leaf senescence.Robatzek and Somssich (2001) A new member of the Arabidopsis WRKY transcription factor family, AtWRKY6, is associated with both senescence- and defence-related processes.
In her postdoctoral work in the Alon lab, Lahav investigated the response of p53 to DNA damage. p53 is highly studied due to its role as "guardian of the genome"; in response to DNA damage, p53 activation may lead to a delay in the cell cycle to allow DNA repair, or may cause the cell to undergo senescence or apoptosis. Previous work had shown that the feedback loop between p53 and its regulator Mdm2 could theoretically cause oscillations in the level of p53. Oscillations were in fact observed in cells exposed to radiation, using a Western blot technique that measures the average p53 level in a population of cells. Lahav developed a novel system for following p53 levels and Mdm2 levels simultaneously in individual living cells and demonstrated that individual cells show discrete pulses of p53 after gamma irradiation.
Shelterin (also called telosome) is a protein complex known to protect telomeres in many eukaryotes from DNA repair mechanisms, as well as to regulate telomerase activity. In mammals and other vertebrates, telomeric DNA consists of repeating double-stranded 5'-TTAGGG-3' (G-strand) sequences (2-15 kilobases in humans) along with the 3'-AATCCC-5' (C-strand) complement, ending with a 50-400 nucleotide 3' (G-strand) overhang. Much of the final double- stranded portion of the telomere forms a T-loop (Telomere-loop) that is invaded by the 3' (G-strand) overhang to form a small D-loop (Displacement- loop). The absence of shelterin causes telomere uncapping and thereby activates damage-signaling pathways that may lead to non-homologous end joining (NHEJ), homology directed repair (HDR), end-to-end fusions, genomic instability, senescence, or apoptosis.
Life history theory is a prominent analytical framework used in evolutionary anthropology, biology, and reproductive ecology that seeks to explain growth and development of an organism through various life history stages of the entire lifespan. The life history stages include early growth and development, puberty, sexual development, reproductive career, and post-reproductive stage. Life history theory is based in evolutionary theory and suggests that natural selection operates on the allocation of different types of resources (material and metabolic) to meet the competing demands of growth, maintenance, and reproduction at the various life stages. Life history theory is applied to reproductive ecology in the theoretical understandings of puberty, sexual growth and maturation, fertility, parenting, and senescence because at every life stage organisms are bound to encounter and cope with unconscious and conscious decisions that hold trade-offs.
When animals are exercised at a relatively high work rate, exercise training promotes an increase in myocardial MnSOD activity. Increased MnSOD activity is required to achieve optimal training-induced protection against both ischemia/reperfusion(IR)-induced cardiac arrhythmias and infarction Using an antisense oligonucleotide against MnSOD to prevent ExTr-induced increases in myocardial MnSOD activity, it was demonstrated that an increase in myocardial MnSOD activity is required to provide training-induced protection against IR- induced myocardial infarction. Using a MnSOD gene silencing approach, reported that prevention of the ExTr-induced increase in myocardial MnSOD resulted in a loss of training-induced protection against IR-mediated arrhythmias. In a mouse model, mitochondrial oxidative stress caused by SOD2 deficiency promoted cellular senescence and aging phenotypes in the skin including an increase in DNA double-strand breaks (see DNA damage theory of aging).
Dr. Ethan Urquhart, Chief of Biology at the Sevarin District Reproduction Centre on Athos, is upset to find that his long-awaited shipment of ovarian tissue cultures from off-planet consists of an unusable mixture of dead and animal tissues. An exclusively male-populated planetary colony, continuing reproduction on Athos relies on uterine replicator technology, but the centuries-old cultures introduced by the original colonists have recently begun deteriorating into senescence. With their entire shipment purchased from the planet Jackson's Whole inexplicably consisting of genetic trash, the Population Council of Athos sends a reluctant Ethan offworld in search of a fresh batch of tissue cultures and (if possible) a refund from the original supplier, House Bharaputra. This is a very daring assignment as it means contact with women, who Athosians are taught are demonic and terrifying.
As cyborgs currently are on the rise some theorists argue there is a need to develop new definitions of aging and for instance a bio-techno- social definition of aging has been suggested. There is a current debate as to whether or not the pursuit of longevity and the postponement of senescence are cost-effective health care goals given finite health care resources. Because of the accumulated infirmities of old age, bioethicist Ezekiel Emanuel, opines that the pursuit of longevity via the compression of morbidity hypothesis is a "fantasy" and that human life is not worth living after age 75; longevity then should not be a goal of health care policy. This opinion has been contested by neurosurgeon and medical ethicist Miguel Faria, who states that life can be worthwhile during old age, and that longevity should be pursued in association with the attainment of quality of life.
The skin thus drawn upon is thrown into folds, especially radiating from the lateral angle of the eyelids; these folds become permanent in senescence, and form the so-called "crow's feet". The Levator palpebræ superioris is the direct antagonist of this muscle; it raises the upper eyelid and exposes the front of the bulb of the eye. In addition, the orbital and palpebral portions can work independent of each other, as in the furrowing of the brows by contraction of the orbital to reduce glare while keeping the eyes open by virtue of the relaxation of the palpebral. Each time the eyelids are closed through the action of the orbicularis, the medial palpebral ligament is tightened, the wall of the lacrimal sac is thus drawn lateralward and forward, so that a vacuum is made in it and the tears are sucked along the lacrimal canals into it.
Working with Laurence D. Mueller, Graves found that population density is an important factor in determining both the immediate chances of survival and the course of natural selection for small organisms such as fruit flies."Population density effects on longevity" Genetica Volume 91, Numbers 1-3 / February 1993 In "Chance, Development, and Aging", Human Biology December 2001, Graves wrote that the explanation of individual patterns of aging must take into account subtle mechanisms such as extensive chance variations in cell number and connections, in cell fates during differentiation, and in physiological patterns that arise during development. Graves has studied the tiny insects for more than a decade in pursuit of greater understanding of senescence, the process of aging. In addition to the study of aging, Graves is interested in the history and philosophy of science as it relates to the biology of race and racism in western society.
The ground hornbills (Bucorvidae) are a family of the order Bucerotiformes, with a single genus Bucorvus and two extant species. The family is endemic to sub-Saharan Africa: the Abyssinian ground hornbill occurs in a belt from Senegal east to Ethiopia, and the southern ground hornbill occurs in southern and East Africa. Ground hornbills are large, with adults around a metre tall. Both species are ground-dwelling, unlike other hornbills, and feed on insects, snakes, other birds, amphibians and even tortoises.Kinnaird Margaret F. and O‘Brien< Timothy G.; The Ecology and Conservation of Asian Hornbills: Farmers of the Forest; pp. 20-23. They are among the longest-lived of all birds,Wasser, D. E. and Sherman, P.W.; “Avian longevities and their interpretation under evolutionary theories of senescence” in Journal of Zoology 2 November 2009 and the larger southern species is possibly the slowest-breeding (triennially) and longest-lived of all birds.
In addition, her work on the survival of Paramecium cultures led to important insights on cellular senescence and methods of genetic transmission Her work at Yale and Princeton was interrupted by World War I. Wartime hysteria cast suspicion on German citizens; as a German citizen working in biology, people began to suspect Erdmann of culturing malicious bacteria. In 1918 Erdmann was accused of poisoning the New Haven drinking water supply and introducing chicken cholera to the U.S. She lost her job at Yale in February 1918, and was jailed from May until September, when she was bailed out by Harrison and a number of female friends. She was then deported to Germany the following spring. Erdmann struggled to find work in Germany, and it was a full year before she got a position at the Institute for Cancer Research at the Charité Hospital of the Friedrich‐Wilhelms University of Berlin.
Stable isotope imaging reveals that C13 and N15 applied to mycorrhizal hyphea webs was found to be readily transferred to the plant via fungal pelotons, leading to a disproportionate amount of these isotopes within the peloton containing plant cells and the peloton itself, but in senescencing pelotons the concentrations of these C13 and N15 containing compound was even more pronounced, and significantly higher than in live pelotons. This indicates that as plant pelotons start to senescence they are loaded with carbon and nitrogen nutritive compounds, hypothetically to be transferred to the plant during lysis. Morphological changes in the hyphea further support this proposition, in that the last morphological change in the peloton before is collapses is a swelling, perhaps due to the increased nutritive compound load. Once digestion is complete, reinfection of the digestive cell will occur shortly after and a new peloton will form, and eventually will be degraded.
A cell that has accumulated a large amount of DNA damage, or one that no longer effectively repairs damage incurred to its DNA, can enter one of three possible states: # an irreversible state of dormancy, known as senescence # cell suicide, also known as apoptosis or programmed cell death # unregulated cell division, which can lead to the formation of a tumor that is cancerous The DNA repair ability of a cell is vital to the integrity of its genome and thus to the normal functionality of that organism. Many genes that were initially shown to influence life span have turned out to be involved in DNA damage repair and protection. Paul Modrich talks about himself and his work in DNA repair. The 2015 Nobel Prize in Chemistry was awarded to Tomas Lindahl, Paul Modrich, and Aziz Sancar for their work on the molecular mechanisms of DNA repair processes.
Studies observing unrestricted sugar intake of females correlated sucrose intake level with maximum accumulation of stored energy reserves. In contrast, sucrose intake level does not correlate with decreased activity or changes in senescence. Carbohydrate feedings of female mosquitoes in a laboratory setting indicated that carbohydrates glucose, fructose, mannose, galactose, sucrose, trehalose, melibiose, maltose, raffinose, melizitose, dextrin, mannitol, and sorbitol are most effective to aid survival; arabinose, rhamnose, fucose, sorbose, lactose, cellobiose, inulin, a-methyl mannoside, dulcitol, and inositol are not used by the species; xylose, glycogen, a-methyl glucoside, and glycerol are used but at a slow metabolic rate; and sorbose could not be metabolized. Feeding with glucose allowed for maximum flight speed while other carbohydrates, such as all pentoses, sorbose, lactose, cellobiose, glycogen, inulin, a-methyl mannoside, dulcitol, and inositol were insufficient to allow flight, indicated by a delay in flight after feeding.
Mortality can be used to define biological aging, which refers to an organism's increased rate of death as it progresses throughout its lifecycle and increases its chronological age. Another possible way to define aging is through functional definitions, of which there are two main types The first describes how varying types of deteriorative changes that accumulate in the life of a post-maturation organism can leave it vulnerable, leading to a decreased ability of the organism to survive. The second is a senescence-based definition; this describes age-related changes in an organism that increase its mortality rate over time by negatively affecting its vitality and functional performance. An important distinction to make is that biological aging is not the same thing as the accumulation of diseases related to old age; disease is a blanket term used to describe a process within an organism that causes a decrease in its functional ability.
It has been found that when the neuroblastoma cells that are resistant to chemotherapy are grown in co-culture with the wild type (WT), or chemotherapy-sensitive cells, the resistance to chemotherapy is conferred to the wild type cells, and thus no cell death or senescence occurs in either cell type, despite the chemotherapeutic treatment. MK has been identified as one of the factors that "transfers" this chemoresistance from the resistant cells to the WT cells. MK is a secreted protein, and is therefore found in the microenvironment (media) of the resistant neuroblastoma cells. Following co-culture experiments and the determination that MK was one of the factors that was conferring chemo- resistance to the wild, non-resistant cell type, the gene for MK was transfected into WT cells to determine if MK was overexpressed in the WT cells themselves, would the cells become resistant to chemotherapy independent of resistant cell influence.
Molecular cloning has led directly to the elucidation of the complete DNA sequence of the genomes of a very large number of species and to an exploration of genetic diversity within individual species, work that has been done mostly by determining the DNA sequence of large numbers of randomly cloned fragments of the genome, and assembling the overlapping sequences. At the level of individual genes, molecular clones are used to generate probes that are used for examining how genes are expressed, and how that expression is related to other processes in biology, including the metabolic environment, extracellular signals, development, learning, senescence and cell death. Cloned genes can also provide tools to examine the biological function and importance of individual genes, by allowing investigators to inactivate the genes, or make more subtle mutations using regional mutagenesis or site-directed mutagenesis. Genes cloned into expression vectors for functional cloning provide a means to screen for genes on the basis of the expressed protein's function.
The hand of an older adult Biogerontology is the sub-field of gerontology concerned with the biological aging process, its evolutionary origins, and potential means to intervene in the process. It involves interdisciplinary research on biological aging's causes, effects, and mechanisms. Conservative biogerontologists such as Leonard Hayflick have predicted that the human life expectancy will peak at about 92 years old, while others such as James Vaupel have predicted that, in industrialized countries, life expectancies will reach 100 for children born after the year 2000. Some surveyed biogerontologists have predicted life expectancies of two or more centuries, with Aubrey de Grey offering the "tentative timeframe" that with adequate funding of research to develop interventions in aging such as Strategies for Engineered Negligible Senescence, "we have a 50/50 chance of developing technology within about 25 to 30 years from now that will, under reasonable assumptions about the rate of subsequent improvements in that technology, allow us to stop people from dying of aging at any age", leading to life expectancies of 1,000 years.
In 1956, a karyotype analysis was carried out on 40 species of Iris, belonging to the subgenera Eupogoniris and Pogoniris. It found that 24-chromosome tall bearded species could e divided into 3 karyotypes of Iris pallida. Iris kashmiriana has 2 pairs of median-constricted marker chromosomes, Iris illyrica, Iris cengialti, and Iris imbricata, lastly Iris variegata, Iris reginae(now classified as a synonym of Iris variegata), and Iris perrieri all have no median-constricted chromosomes. In 1990, 'Iriskashmirianin' flavonoid was found in Iris kashmiriana by Kacheroo.J.B. Harborne In 1996, a study was carried out on the rhizomes of Iris kashmiriana, two new isoflavones, 'isocladrastin' and 'kashmigenin', were found. In 1998, a study was carried out on flower senescence (aging) in Iris kashmiriana. In 2008, a chemical study was carried out on the rhizomes of Iris kashmiriana led to the isolation of three isoflavones characterized as (4'-hydroxy-8-methoxy-6,7-methylenedioxyisoflavone) 'isonigricin', (5,6-dihydroxy-4',7-dimethoxyisoflavone) 'isoirisolidone', and (5,7-dihydroxy-4',6-dimethoxyisoflavone) 'irisolidone'. In June 2012, a phytochemical study was carried out on 5 iris species growing in Kashmir, India.
The Twilight Years, a 1972 novel by Sawako Ariyoshi, sold over a million copies in her home country and was praised by the Japan-studies community in foreign countries as a singular novel, "the closest representation of modern Japanese life" according to Donald Keene and a forthright, insightful work into the experience of modern Japanese women. The work, which begins with the married protagonist's father-in-law seemingly doddering around in senility on a winter street underdressed, deals with the twin issues of Aging of Japan and role of women in Japan, who were/are de facto expected to be caretakers of elderly parents or grandparents in a household. Although the novel at times digresses into what may be characterized as a mere extended complaint about the subservient role women experience in Japan (most poignantly, as the protagonist realizes that her husband may very well forget her name as he grows dodderingly old), the work was prescient in that it foreshadowed the current demographic crisis facing Japan, i.e. a population rapidly entering old age without sufficient young workers to take care of the problems of advanced senescence.
El-Deiry made the discoveries of the consensus binding site for p53 and the discovery of WAF1 while working with Bert Vogelstein at Johns Hopkins University. p21(WAF1) was the first mammalian cell cycle inhibitor to be discovered, and was found independently by Wade Harper and Steve Elledge as a CDK2-interacting protein p21(CIP1), Yue Xiong and David Beach as a cyclin- CDK-PCNA interacting protein (p21), and as a senescence derived inhibitor by Noda. Multiple CDK inhibitors have become approved as cancer therapeutics, including palbociclib, abemaciclib and ribociclib. In 2017, El-Deiry's group discovered a micro-RNA family that inhibits CDK4/6. In total, El-Deiry has >61,000 citations and an H-index of 114 according to Google Scholar. He was recognized through an award from the American Cancer Society in 2016. As an independent investigator at University of Pennsylvania, El-Deiry discovered TRAIL death receptor 5 (DR5) in 1997. His group was first to combine gene silencing with bioluminescence imaging in vivo and to use molecular imaging for drug screening. His group created a knockout mouse of death receptor 5 (DR5) that shows reduced apoptosis in vivo after exposure to gamma-radiation, and increased tumor susceptibility in tumor-prone genetic backgrounds.

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