The Marind Anim of New Guinea bury senescent elders alive.
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Germany is senescent, with a median age of about 46.
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For instance, DNA damage causes increased senescent cell accumulation, Kirkland said.
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To see what role, if any, senescent cells were playing in the their diminishing brainpower, Dr Baker genetically altered some mice such that their senescent cells could be eliminated with a twice-weekly dose of a specific chemical.
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Unity targets senescent cells—cells that, as they age, start producing a colorless, odorless, noxious goo called SASP , which Unity's researchers call "the zombie toxin," because it makes other cells senescent and spreads chronic inflammation throughout the body.
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Another study found that senescent cells contribute to diseases like atherosclerosis and arthritis.
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Basically, most cells divide and replicate some fifty-plus times before becoming senescent.
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In animal trials, clearing senescent cells from an organism has shown promising results, as a groundbreaking aging study on destroying senescent cells published in 2016 by Jan van Deursen, a molecular biologist at the Mayo Clinic and fellow Unity Biotechnology co-founder, demonstrated.
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Or the protein could work through senescent cells, which accumulate in aging tissues and cause inflammation.
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Those processes include inflammation, changes in your DNA, cell damage or dysfunction and the accumulation of senescent cells.
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Not nearly as inactive as the name suggests, senescent cells contribute to chronic inflammation and interfere with protective collagens.
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One study cited by Citi said the elimination of senescent cells could increase the human lifespan by about 35%.
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Our immune system clears out senescent cells on a regular basis, but this process becomes less effective over time.
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So an intervention that targets senescent cells could attenuate other aging processes as well, according to the new paper.
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In humans, senescent cells play a role in many age-related chronic diseases like diabetes, cardiovascular disease and arthritis.
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As we age, we accumulate senescent cells, which are damaged cells that resist dying off but stay in our bodies.
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Senolytic drugs are agents capable of killing problem-causing senescent cells in your body without harming your normal, healthy cells.
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Ultimately, the thinking is that such a drug can destroy senescent cells, effectively halting or reversing osteoarthritis in the knee.
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For years it was assumed that, apart from their refusal to divide, senescent cells were otherwise identical to their replicating compatriots.
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In contrast, mice whose brains were full of senescent cells approached the objects tentatively, as if they had never seen them before.
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Tellingly, the accumulation of abnormal amounts of senescent cells tends to happen where disease occurs, including in our lungs, joints, and arteries.
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One study in 2016 reported that senescent cells in the kidneys and heart produce a protein that causes nearby healthy tissues to deteriorate.
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Specifically, when lab mice had senescent cells removed, they demonstrated healthier joints and better eyesight as they aged than those that did not.
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Then, last year, the researchers demonstrated in a study in Aging Cell that clearing senescent cells in mice can improve their vascular health.
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PAI-1 is one of the inflammatory agents that senescent cells typically secrete, and it's possible that the Amish mutation disrupts that process.
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Elimination of senescent cells can counter chronic inflammation, said Steven N. Austad, director of aging studies at the University of Alabama at Birmingham.
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Trump has turned out to be the Norma Desmond of authoritarians, a senescent has-been whose delusions are propped up by obsequious retainers.
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That left a subgroup of mice that were still genetically predisposed to neurological diseases, but which also had their brains rinsed of senescent cells.
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Another anti-aging start-up is San Francisco-based Unity Biotechnology, which is developing medicines that selectively target and eliminate so-called senescent cells.
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One company, Unity Biotechnology, aims to be the first to demonstrate that removing senescent cells can cure human diseases, said its president, Nathaniel David.
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It worked quite well, clearing out about 60 to 70 percent of senescent cells in middle-aged mice (which for mice is about 12 months).
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Senescent cells play a role in many age-related chronic diseases, such as diabetes, cardiovascular disease, most cancers, dementia, arthritis, osteoporosis and blindness, Kirkland said.
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"Senescent cells are really one of the first bona fide targets of aging that we've found we've been able to do something about," Perrott said.
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Taking aim at senescent cells is a treatment paradigm being used not only by Unity Biotechnology, but also by research hospitals in the United States.
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Rather than indulging mobs of senescent villagers, another suggests, the government should give the authority to resolve petty disputes to nazims, the lowliest of elected officials.
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One anti-senescent drug is in a clinical trial on humans with osteoarthritis in their knees, and researchers expect data in the first quarter of next year.
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Since it is not possible to do pre-emptive genetic engineering on humans, some pharmaceutical method of clearing out senescent cells will have to be developed instead.
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America's nuclear arsenal is in the hands of a senescent Twitter troll, but those with political power have refused to treat this fact as a national emergency.
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This research strongly suggests that the accumulation of senescent cells is largely a bad thing; not only do they shorten life, they shorten the healthy parts of our lives.
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Another consequence of aging is the accumulation of so-called senescent cells, normal cells that stop dividing, contribute to tissue aging and secrete substances like cytokines that induce inflammation.
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It has been long known that cultured human cells seem able to replicate no more than 40 to 60 times (called the Hayflick limit) before they stop and become senescent.
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Or any of the moments when the usually senescent Aunt Maggie Far Away (Fionnula Flanagan) swerves into focus, with visions of those baleful spirits, the banshees, that feel all too real.
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A combination of two drugs, dasatinib and quercetin, was shown in a Mayo Clinic study in obese mice to remove senescent cells and permit cell growth to resume in the brain.
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Eventually, after a few hundred years of technology optimization, with a combination of reprogramming, hormesis-stimulating molecules, senescent cell deletion, and organ replacement, we could live thousands of years or more.
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Assuming Unity Biotechnology's phase 1 trial goes smoothly, David said the next step will be further trials to determine what effects the company's senolytic drugs have on senescent cells in patients.
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The details: Among the most promising drugs under development are ones that would attack "senescent cells," which Citi says are blamed for numerous age-related diseases including arthritis, retinal degeneration and Alzheimer's.
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They develop an odd, culturally freighted relationship — the senescent past reconciling itself to Europe's future — until the last act blows up the script's character-building for the sake of a shock ending.
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What's more, van Deursen demonstrated that killing senescent cells in mice extended their lifespans by as much as one-third, while improving kidney function and making their hearts more resilient to stress.
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When the mice were four months old, Dr Baker collected brain tissue from some, and found senescent cells accumulating in the hippocampus, a seahorse-shaped region of the brain involved with learning and memory.
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Indeed, the next project in his lab is to explore whether clearing senescent cells from the brains of mice that are already suffering from the murine version of Alzheimer's might allow their already damaged brains to recover.
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To explore the role of senescent cells in aging, a team led by Jan van Deursen, Chair of Biochemistry and Molecular Biology at Mayo Clinic, created a mouse model in which these cells could be flushed out.
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Other technologies that will complement this include the ability to kill off old, zombie senescent cells and induce the benefits of diet and exercise with molecules called rapalogs and NAD booster, and tech we can't yet dream of.
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The moment Bloomberg qualified for Wednesday's debate with a last-minute poll showing him at second place nationwide, however, the calculus threatened to change: In the hole left by a senescent Joe Biden, Bloomberg was now a serious threat.
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Going into the study, the Mayo Clinic researchers asked themselves two important questions: are these senescent cells important drivers of disease, and if so, can their removal be used as a therapeutic mechanism to treat patients of age-related diseases?
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While Newman does think that senescent cell research is a promising field for treating some of the effects of aging, he emphasizes that just because a drug proves effective in animals does not necessarily mean it will translate successfully to human beings.
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New work led by Darren Baker, a biologist at the Mayo Clinic in Minnesota, published in Nature this week, suggests the accumulation of senescent cells within the brains of mice causes the animals to develop neurodegenerative diseases—and that clearing out these cells can help prevent them.
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Founded in 21999 by David and a group of professors in the biological sciences, Unity Biotechnology's research focuses in particular on senescent cells — older cells that have stopped dividing and appear to be one of the causes of the onset of the diseases associated with aging.
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They are willing, out of some complex mix of ambition, resentment, cynicism and rationalization, to endanger all of our lives — all of our children's lives — by refusing to tell the country what they know about the senescent fool who boasts of the size of his "nuclear button" on Twitter.
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During one of many RAADfest talks, he pulled up a slide citing new research in the elite Journal of the American Medical Association, outlining the dangers of "zombie-like" senescent cells that spew harmful proteins, and the potential of senolytic drugs to curb the harm done—progress, but again, in mice.
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Taking aim at senescent cells is a treatment paradigm being used not only by Unity Biotechnology, but also by research hospitals in the U.S. A team at the Kogod Center on Aging at the Mayo Clinic is currently testing the use of senolytic drugs in treating chronic kidney disease in humans.
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Senescent cells are especially common in skin and adipose tissue. Senescent cells are usually larger than non-senescent cells. Transformation of a dividing cell into a non- dividing senescent cell is a slow process that can take up to six weeks. The secretome of senescent cells is very complex.
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Senescent-like aging CD8+ cytotoxic T-lymphocytes become more innate in structure and function, resembling NK cells. Immune system cells can be recruited by SASP to senescent cells, after which the SASP from the senescent cells can induce the immune system cells to become senescent. Chimeric antigen receptor T cells have been proposed as an alternative means to senolytic drugs for the elimination of senescent cells. Urokinase receptors have been found to be highly expressed on senescent cells, leading researchers to use chimeric antigen receptor T cells to eliminate senescent cells in mice.
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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.
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CD8+ cytotoxic T-lymphocytes also use NKG2D receptors to detect senescent cells, and promote killing similar to NK cells. Aging of the immune system (immunosenescence) results in a diminished capacity of the immune system to remove senescent cells, thereby leading to an increase in senescent cells. Chronic inflammation dues to SASP from senescent cells can also reduce the capacity of the immune system to remove senescent cells. T cells, B cells, and NK cells have all been reported to become senescent themselves.
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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. Natural killer cells can use NKG2D receptors to detect senescent cells, and kill those cells using perforin pore-forming cytolytic protein. CD8+ cytotoxic T-lymphocytes also use NKG2D receptors to detect senescent cells, and promote killing similar to NK cells.
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Senescent cells contribute to the aging phenotype, including frailty syndrome, sarcopenia, and aging-associated diseases. Senescent astrocytes and microglia contribute to neurodegeneration.
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In animal studies, navitoclax was found to be a senolytic agent, inducing apoptosis in senescent, but not non-senescent cells. Oral administration of ABT263 to either sublethally irradiated or normally aged mice reduced senescent cells, including senescent bone marrow hematopoietic stem cells and senescent muscle stem cells. This depletion mitigated total- body irradiation-induced premature aging of the hematopoietic system and rejuvenated the aged hematopoietic stem cells and muscle stem cells in normally aged mice. On September 19, 2018, an article was published in Nature about using this drug to kill senescent glial cells in mice.
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Chronic inflammation associated with aging has been termed inflammaging, although SASP may be only one of the possible causes of this condition. SASP factors stimulate the immune system to eliminate senescent cells. SASP factors from senescent cells reduce nicotinamide adenine dinucleotide (NAD+) in non- senescent cells, thereby reducing the capacity for DNA repair and sirtuin activity in non-senescent cells. SASP induction of the NAD+ degrading enzyme CD38 on non-senescent cells may be responsible for most of this effect.
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Interventions to increase senescent cell surface ligands of the Natural Killer cell receptor NKG2D have been proposed as a senolytic therapy to remove senescent cells.
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Senescent cells can be phagocytized by neutrophils as well as by macrophages. Senolytic drugs which induce apoptosis in senescent cells rely on phagocytic immune system cells to remove the apoptosed cells. Natural killer cells can use NKG2D killer activation receptors to detect the MICA and ULBP2 ligands which become upregulated on senescent cells. The senescent cells are killed using perforin pore-forming cytolytic protein.
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Giving dasatinib and quercetin to mice eliminated senescent cells and caused a long-term resolution of frailty. A study of fourteen human patients suffering from idiopathic pulmonary fibrosis (a disease characterized by increased numbers of senescent cells) given dasatinib and quercetin showed improved physical function and evidence of reduced senescent cells.
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Targeting senescent cells is a promising strategy to overcome age-related disease, simultaneous alleviate multiple comorbidities, and mitigate the effects of frailty. Removing the senescent cells by inducing apoptosis is the most straightforward option, and there are several agents that have been shown to accomplish this. Some of these senolytic drugs take advantage of the senescent-cell anti-apoptotic pathways (SCAPs); knocking out expression of the proteins involved in these pathways can lead to the death of senescent cells, leaving healthy cells.
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Dasatinib has been shown to eliminate senescent cells in cultured adipocyte progenitor cells. Dasatinib has been shown to induce apoptosis in senescent cells by inhibiting Src kinase, whereas quercetin inhibits the anti-apoptotic protein Bcl-xL. Administration of dasatinib along with quercetin to mice improved cardiovascular function and eliminated senescent cells. Aged mice given dasatinib with quercetin showed improved health and survival.
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Senescent adipose progenitor cells in subcutaneous adipose tissue has been shown to suppress adipogenic differentiation. Reduced adipogenesis in obese persons is due to increased senescent cells in adipose tissue rather than reduced numbers of stem/progenitor cells.
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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.
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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.
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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.
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When the immune system cannot clear senescent cells at the rate at which senescent cells are being produced, possibly as a result of the decline in immune function with age, accumulation of these cells leads to a disruption in tissue homeostasis.
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SASP may also play a role in tissue regeneration by signaling for senescent cell clearance by immune cells, allowing progenitor cells to repopulate tissue. In development, SASP also may be used to signal for senescent cell clearance to aid tissue remodeling.
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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.
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Baar, Marjolein P., et al. "Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging." Cell 169.1 (2017): 132-147. Other research conducted by Campisi has shown that factors secreted by senescent cells can also stimulate growth and angiogenic activity in nearby cells.
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An online SASP Atlas serves as a guide to the various types of SASP. SASP is one of the three main features of senescent cells, the other two features being arrested cell growth, and resistance to apoptosis. SASP factors can include the anti-apoptotic protein Bcl-xL, but growth arrest and SASP production are independently regulated. Although SASP from senescent cells can kill neighboring normal cells, the apoptosis-resistance of senescent cells protects those cells from SASP.
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Chimeric antigen receptor natural killer cells have been proposed as an allogeneic means of eliminating senescent cells.
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Senescent cells within a multicellular organism can be purged by competition between cells, but this increases the risk of cancer. This leads to an inescapable dilemma between two possibilities—the accumulation of physiologically useless senescent cells, and cancer—both of which lead to increasing rates of mortality with age.
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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.
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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.
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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.
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Extension publications (MU), 2008. Senescent corn leaves are an important plant part for the growth and development of C. carbonum, because it provides biochemicals required for the formation of perithecia, asci and ascospores.Fries, R.E. and R.R. Nelson, The influence of extracts from senescent corn leaves on sexual reproduction in Cochliobolus carbonum. Canadian Journal of Microbiology, 1972.
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LIM and senescent cell antigen-like-containing domain protein 1 is a protein that in humans is encoded by the LIMS1 gene.
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Inflammation is only triggered by certain pathogen- or damage-associated molecular patterns (PAMPs or DAMPs), the removal of senescent cells is non-inflammatory.
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The habitat is Fagus sylvatica and Quercus robur forest with mature and senescent trees, and evergreen oak forest of Quercus suber and Quercus ilex.
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Soluble urokinase plasminogen activator receptor (suPAR) has been found to be a biomarker of inflammation. Elevated suPAR is seen in chronic obstructive pulmonary disease, asthma, liver failure, heart failure, cardiovascular disease, and rheumatoid arthritis. Smokers have significantly higher suPAR compared to non-smokers. Urokinase receptors have been found to be highly expressed on senescent cells, leading researchers to use chimeric antigen receptor T cells to eliminate senescent cells in mice.
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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.
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However, it remains as the most widely used biomarker for senescent and aging cells, because it is easy to detect and reliable both in situ and in vitro.
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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.
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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.
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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.
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SASP can aid in signaling to immune cells for senescent cell clearance, with specific SASP factors secreted by senescent cells attracting and activating different components of both the innate and adaptive immune system. But with chronic inflammation, immune system function may be suppressed. SASP can also play a beneficial role by promoting wound healing. However, in contrast to the persistent character of SASP in chronic inflammation, beneficial SASP in wound healing is transitory.
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The dark coloration appeared to be due to higher melanin levels and activity of tyrosinase in the senescent fibroblasts than in the controls, potentially related to lower SDF1 expression. Patients were then administered six weekly treatments of microneedle fractional radiofrequency aimed at eliminating dermal senescent fibroblasts; this led to a marked decrease in epidermal pigmentation compared to baseline, accompanied by a decrease in the synthesis of collagen and the normalization of suppressed SDF1 expression.
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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).
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The doctors said his brain was senescent from several small strokes and hardening of the arteries. His last words, aside from the repeated word "God", were "God bless... God damn", according to his wife, Helen.
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The removal of aggregated p16 INK 4A positive senescent cells can delay tissue dysfunction and ultimately extend life. In the 2011 Nature paper by Baker et al. a novel transgene, INK-ATTAC, was used to inducibly eliminate p16 INK4A-positive senescent cells by action of a small molecule- induced activation of caspase 8, resulting in apoptosis. A BubR1 H/H mouse model known to experience the clinicopathological characteristics of aging- infertility, abnormal curvature to the spine, sarcopenia, cataracts, fat loss, dermal thinning, arrhythmias, etc.
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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.
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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.
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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.
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Saretzki, G., Feng, J., von Zglinicki, T., and Villeponteau, B. (1998). Similar gene expression pattern in senescent and hyperoxic-treated fibroblasts. The journals of gerontology Series A, Biological sciences and medical sciences 53, B438-442.Villeponteau, B. (1997).
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Multicellular organisms replace worn-out cells through cell division. In some animals, however, cell division eventually halts. In humans this occurs, on average, after 52 divisions, known as the Hayflick limit. The cell is then referred to as senescent.
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Ironically, these secreted factors can facilitate the development of cancer in surrounding premalignant cells.Krtolica, Ana, et al. "Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging." Proceedings of the National Academy of Sciences98.21 (2001): 12072-12077.
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Wavy edged and thin, 5 to 15 cm long with a long tip. An occasional senescent red leaf may be seen. Small oil dots may be seen under a lens. The midrib is raised under the leaf, but sunken on the upper side.
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Glossy green above, somewhat duller below. An occasional orange senescent leaf will be seen in the canopy. Leaves 5 to 12 cm long, elliptic in shape, toothed or sometimes not toothed. Leaf stalks 5 to 13 mm long, channeled on the upper surface.
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Minute, usually rod-shaped or granular and yellow or brown colored chloroplasts are characteristic of Dinophysis. The chloroplasts have stacks of three thylakoids and an internal pyrenoid. In senescent cells, chloroplasts tend to aggregate in the middle and form orange patches. Some Dinophysis spp.
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At Middle Brother National Park, there are two senescent individuals. Benaroon is 64 metres tall and 4.1 metres diameter at breast height. Bird Tree, nearby is 69 metres tall 3.59 metres diameter at breast height. An 85-metre tall blackbutt was felled near Bulli.
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Elaeocarpus kirtonii leaves A large and often dominant tree, growing to 45 metres tall, and over 2 metres in diameter. The outer bark is silvery grey and thin, with small pustules. The tree base is significantly buttressed. Another identifying feature is the senescent red leaves.
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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.
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Time wrote of Winters in its October 11, 1972, review, "Winters is one of the few young actresses with comic timing."Senescent Saint, Time, October 11, 1971 Winters continued acting with starring roles in film and episodic television including Blue Sunshine (1978), The Outing (1987), and Lottery!.
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Somatic cells that have divided many times will have accumulated DNA mutations and would be more susceptible to becoming cancerous if cell division continued. As such, it is becoming apparent that senescent cells undergo conversion to an immunologic phenotype that enables them to be eliminated by the immune system.
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Hardisty and Potter, 1971a,b. The sedentary and phytophagous larval period of all lampreys is spent in the sandy silt substratum of cool streams.Moore and Mallatt, 1980. Coloration of live mountain brook lamprey did not change between the ammocoete and senescent periods and ranged from butterscotch to olive brown.
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Rubtsov, M.A., Polikanov, Y.S., Bondarenko, V.A., Wang, Y.H., and Studitsky, V.M. (2006). Chromatin structure can strongly facilitate enhancer action over a distance. Proceedings of the National Academy of Sciences of the United States of America 103, 17690-17695. Villeponteau also studied human cell aging using senescent human cells.
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The fungus grows on the senescent culms of Juncus roemerianus. Because the fruit bodies are found on the middle and upper parts of the culm, typically between above the rhizome, it is considered a terrestrial organism. M. carolinensis is found on the Atlantic Coast of the United States.
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Fur of senescent river otters may become white-tipped, and rare albinos may occur. The North American river otter is sexually dimorphic. Males are, on average, 5% larger than females. In Idaho, juvenile, yearling, and adult males averaged 8, 11, and 17% heavier, respectively, than females of the same age.
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The disease cycle starts with dissemination of ascospores after which germination pycnidia rapidly develop. Pycnidiaspores quickly disperse by rain splashes are responsible for reinfection over short distances. Consequently, production of pseudothecia is initiated on senescent tissues. After rainfall, ascospores are released from the pseudothecia and disperse by wind over long distances.
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They show prominent venation, particularly on the underside. Another identifying feature of this and other Elaeocarpus trees is the senescent red leaves. White flowers appear on paired racemes in November and December. The fruit is a black- or (immature) maroon-coloured drupe, 9 mm long, maturing from March to October.
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This prevents the incremental shortening of telomeres that is implicated in aging and eventual cell death. In this way, the cells circumvent the Hayflick limit, which is the limited number of cell divisions that most normal cells can undergo before becoming senescent. The result is unlimited cell division and immortality.
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Habitat: Fagus and Quercus ancient woodland with over-mature and senescent trees. Arboreal, but descends to visit flowers of white umbellifers, Cornus sanguinea, Crataegus, Photinia, Prunus spinosa, Ribes alpina, Rubus idaeus, Sorbus aucuparia, Sorbus aria.de Buck, N. (1990) Bloembezoek en bestuivingsecologie van Zweefvliegen (Diptera, Syrphidae) in het bijzonder voor België. Doc.Trav. IRSNB, no.
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During the first two years after germination, phosporus compounds concentrated in the leaves. In senescent plants, the phosporus content of the leaves was lower, and phosphorus had moved to the seeds. Such a change over the life cycle is probably representative for many other species in the fynbos and other nutient-poor soils.
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The leaves turn red when senescent, hence the common name of bleeding heart. Flowers are yellow green to red, 2 to 10 cm long. Appearing on racemes mostly in the months of September to December. The fruit matures from December to March, being a two-lobed capsule with an oily yellow aril.
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Among ten known human RAET1/ULBP genes, six encode functional proteins: RAET1E/ULBP4, RAET1G/ULBP5, RAET1H/ULBP2, RAET1/ULBP1, RAET1L/ULBP6, RAET1N/ULBP3. In mice, proteins from orthologous RAET1/ULBP family fall into three subfamilies: Rae-1, H60, and MULT-1. ULBP2 is a stress- induced ligand often found on senescent cells.
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After many divisions, the telomeres reach a critical length and the cell becomes senescent. It is at this point that a cell has reached its Hayflick limit. Hayflick was the first to report that only cancer cells are immortal. This could not have been demonstrated until he had demonstrated that only normal cells are mortal.
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The clinical symptoms are caused by immunological abnormalities (figure 2). These include deficiency in CD27+ B memory cells, overrepresentation of CD10+ transitional B cells, expanded effector (CCR7-) T cells, expanded CD57+ senescent CD8+ T cells, and alterations in serum immunoglobulin concentrations, most with normal to elevated concentrations of IgM and reduced concentrations of IgA.
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Insects and birds avoid the fruit flesh, perhaps because of its astringent properties, that are much reduced in senescent fruits, but still perceptible to the human palate. Apparently mature fruits severed from the tree while still hard often fail to develop the desired climacteric changes in terms of reduced astringency and a texture reminiscent of egg yolk.
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A. arkos and A. argentus are currently listed as endangered. The main threats to these species, indeed all species of Antechinus, are habitat destruction and introduced animals. Deforestation and habitat destruction removes the complex understorey habitat which Antechinus require for protection from predators and for food. Antechinus also nest in tree hollows, which only form in senescent trees.
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PASLI disease is a rare genetic disorder of the immune system. PASLI stands for “p110 delta activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency.” The immunodeficiency manifests as recurrent infections usually starting in childhood. These include bacterial infections of the respiratory system and chronic viremia due to Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV).
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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.
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Navitoclax entered clinical trials, and showed promise in haematologic cancers, but was stalled when it was found to cause thrombocytopenia (severe loss of platelets), which was discovered to be caused by the platelets' requirement for Bcl-xL for survival. Subsequently, it was reported that ABT-737 specifically induces apoptosis in senescent cells in vitro and in mouse models.
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Biliverdin results from the breakdown of the heme moiety of hemoglobin in erythrocytes. Macrophages break down senescent erythrocytes and break the heme down into biliverdin along with hemosiderin, in which biliverdin normally rapidly reduces to free bilirubin. Biliverdin is seen briefly in some bruises as a green color. In bruises, its breakdown into bilirubin leads to a yellowish color.
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Not all types of human cancer have increased telomerase activity. 90% of cancers are characterized by increased telomerase activity. Lung cancer is the most well characterized type of cancer associated with telomerase. There is a lack of substantial telomerase activity in some cell types such as primary human fibroblasts, which become senescent after about 30–50 population doublings.
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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.
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It is also being investigated for plaque psoriasis, alopecia areata, relapsed diffuse large B-cell lymphoma, and peripheral T-cell lymphoma. In Feb 2016, a phase III trial for pancreatic cancer was terminated due to insufficient efficacy. Eight weeks-treatment with ruxolitinib blunted senescent cell-mediated inhibition of adipogenesis and increased insulin sensitivity in 22-month-old mice. As of September 2019.
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Telomerase restores short bits of DNA known as telomeres, which are otherwise shortened when a cell divides via mitosis. In normal circumstances, where telomerase is absent, if a cell divides recursively, at some point the progeny reach their Hayflick limit, which is believed to be between 50–70 cell divisions. At the limit the cells become senescent and cell division stops.Siegel, L (2013).
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The DNA damage response (DDR) arrests cell cycle progression until DNA damage, such as double-strand breaks (DSBs), are repaired. Senescent cells display persistent DDR that appears to be resistant to endogenous DNA repair activities. The prolonged DDR activates both ATM and ATR DNA damage kinases. The phosphorylation cascade initiated by these two kinases causes the eventual arrest of the cell cycle.
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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.
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This protein is localized in the cytoplasm and nucleus. It is responsible for effecting specific muscle adherens junctions and mechanosensory functions of touch receptor neurons. The protein sequence in the LIM domains are linked with very short interdomain peptides and c-terminal extension with high amounts of positive charges. The protein has multiple functions even presenting in senescent enrythrocyte antigens.
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Although older individuals manage to achieve pressures necessary to affect a successful swallow, despite a reduction in overall maximum tongue strength, they achieve these pressures more slowly than young swallowers. It has been suggested that the slowness that characterizes senescent swallowing may reflect the increased time necessary to recruit sufficient motor units to generate pressures necessary to operate an effective, safe swallow.
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A Clockwork Orange was written in Hove, then a senescent seaside town. Burgess had arrived back in Britain after his stint abroad to see that much had changed. A youth culture had grown, including coffee bars, pop music and teenage gangs.A Clockwork Orange (Penguin Modern Classics) (Paperback) by Anthony Burgess, Blake Morrison xv England was gripped by fears over juvenile delinquency.
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It is capable of catching live fish. Based on the extreme lack of aging symptoms and lack of age related decline, these turtles are considered a negligibly senescent species. Blanding's turtle is a timid turtle and may plunge into water and remain on the bottom for hours when alarmed. If away from water, the turtle will withdraw into its shell.
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Or they can be destroyed by gene therapy to introduce "suicide genes" that only kill senescent cells. # Protein cross-linking can largely be reversed by drugs that break the links. But to break some of the cross-links we may need to develop enzymatic methods. # Extracellular garbage (like amyloid) can be eliminated by vaccination that gets immune cells to "eat" the garbage.
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Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose. Ursolic acid enhances mouse liver regeneration after partial hepatectomy. Ursolic acid enhances the cellular immune system and pancreatic beta-cell function in streptozotocin-induced diabetic mice fed a high-fat diet. UA increased skeletal muscle mass, as well as grip strength and exercise capacity.
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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.
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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.
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Several studies have found a positive relationship between measures of wild lupine and Karner blue butterfly abundance. However, available evidence suggests that senescent wild lupine is a poor larval food source. The effects of other phenological stages are more ambiguous. In west-central Wisconsin, Karner blue butterfly abundance was negatively associated with the abundance of reproductive lupine and positively related with the frequency of immature wild lupine.
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Unlike the obvious enhanced immune activation present in CTLA-4 and PD-1 gene knockout mice, KLRG1 knockout mice initially were found to have no abnormal features, though were subsequently found to have enhanced immunity in a tuberculosis challenge model. The characterization of KLRG1 as a “senescent” marker, but other co-inhibitory receptors as “exhaustion” markers, has contributed to relatively fewer studies on this molecule.
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Here the ground is damp and parts of Birch Copse barely see daylight. While some of the tall pines seem senescent, other plantation firs are green and vibrant. Many varieties of fungi can be seen in profusion in October, but dead-wood fungi are common enough throughout the year. At the southeast edge of the forest are good examples of Sweet Chestnut and Yew.
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Studies of cell cultures of senescent human umbilical vein endothelial cells have shown that both fisetin and quercetin induce apoptosis by inhibition of Bcl-xL. Fisetin has roughly twice the senolytic potency as quercetin. Small molecule Bcl-xL inhibitor that directly binds to Bcl-xL and releases their partner such as Bax, a proapoptotic protein, has been suggested as an anticancer strategy via inducing of apoptosis.
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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.
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They are found at depths from , but average is about . In Atlantic waters, most snow crabs are found at depths of . Where male and female snow crabs are found in the ocean, depths may vary. Small adult and senescent adult males occur mainly at intermediate depths over much of the year, while large and hardy adult males are found mostly at depths greater than .
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The Utah valvata snail is univoltine (produces one group of eggs per year) with a lifespan of about 1 year. Reproduction and spawning occur asynchronously between March and October, depending on habitat, with the majority of young spawned between August and October. Emergence of a new cohort follows approximately 2 weeks after oviposition, and senescent snails (i.e., those approximately 374 days old) die shortly after reproduction.
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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.
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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.
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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.
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Macrophages are professional phagocytes in innate immune responses. Activated macrophages are effective killers that eliminate pathogens in both innate and adaptive immune responses, and are also important in tissue homeostasis, through the clearance of senescent cells, and in remodeling and repair of tissue after inflammation. The number of macrophages increases with the progression of caries and is always higher than that of DCs at all stages of the caries invasion.
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In 2010, the company began construction of the world's first commercial algal bio-refinery, a project that was awarded more than $100 million in federal funding. In 2011, David co-founded Unity Biotechnology (NASDAQ: UBX), a company dedicated to lengthening human healthspan by selectively clearing senescent cells from the body. UNITY is creating medicines that target multiple diseases of aging. David is currently the President of Unity Biotechnology.
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The actual form of the plant is rather variable, probably influenced by its environment; in one form the leaves are up to long, while in another they are stubby and clustered at the end of the stems. The stems vary as well, sometimes being hardened and blackish, contrasting with the bright green growth of the foliage in spring and summer. The leaves may become reddened or senescent in the winter.
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Natural antibodies recognize these clusters on senescent erythrocytes. Protection by HbAS involves the enhancement of not only innate but also of acquired immunity to the parasite. Prematurely denatured sickle hemoglobin results in an upregulation of natural antibodies which control erythrocyte adhesion in both malaria and sickle cell disease. Targeting the stimuli that lead to endothelial activation will constitute a promising therapeutic strategy to inhibit sickle red cell adhesion and vaso-occlusion.
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The oldest trees are in the Colbert forest (). It is a parcel, in two pieces, the main stand in a regeneration from the end of the 17th century. These are classified as a directed biological reserve; lumber is no longer taken in order to favour biodiversity around deadwood and senescent trees. The Colbert high forest spanned in 1976, of which 60 ha were regenerated from 1976 to 2001.
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Phagocytosis of a bacterium, showing the formation of phagosome and phagolysosome In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs). A phagosome is formed by the fusion of the cell membrane around a microorganism, a senescent cell or an apoptotic cell. Phagosomes have membrane-bound proteins to recruit and fuse with lysosomes to form mature phagolysosomes.
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Phagosomes degrade senescent cells and apoptotic cells to maintain tissue homeostasis. Erythrocytes have one of the highest turnover rates in the body, and they are phagocytosed by macrophages in the liver and spleen. In the embryo, the process of removing dead cells is not well-characterised, but it is not performed by macrophages or other cells derived from hematopoietic stem cells. It is only in the adult that apoptotic cells are phagocytosed by professional phagocytes.
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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.
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Salix arctica, the Arctic willow, is the larva's primary host plant. G. groenlandica spends much of its life in a larval state, and food resources are necessary for development of the larvae. Salix arctica, the Arctic willow, is the primary host plant and food source for this species. The larvae may also feed on plants of other families, such as the flowers of Saxifraga oppositifolia and the senescent leaves of Dryas integrifolia.
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Hemolysis is sometimes called hematolysis, erythrolysis, or erythrocytolysis. The words hemolysis () and hematolysis () both use combining forms conveying the idea of "lysis of blood" (hemo- or hemato- + -lysis). The words erythrolysis () and erythrocytolysis () both use combining forms conveying the idea of "lysis of erythrocytes" (erythro- ± cyto- + -lysis). Red blood cells (erythrocytes) have a short lifespan (approximately 120 days), and old (senescent) cells are constantly removed and replaced with new ones via erythropoiesis.
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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.
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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".
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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.
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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.
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Males become senescent and die a few weeks after mating. The eggs have large yolks; cleavage (division) is superficial and a germinal disc develops at the pole. During gastrulation, the margins of this grow down and surround the yolk, forming a yolk sac, which eventually forms part of the gut. The dorsal side of the disc grows upwards and forms the embryo, with a shell gland on its dorsal surface, gills, mantle and eyes.
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Phagosomes are large enough to degrade whole bacteria, or apoptotic and senescent cells, which are usually >0.5μm in diameter. This means a phagosome is several orders of magnitude bigger than an endosome, which is measured in nanometres. Phagosomes are formed when pathogens or opsonins bind to a transmembrane receptor, which are randomly distributed on the phagocyte cell surface. Upon binding, "outside-in" signalling triggers actin polymerisation and pseudopodia formation, which surrounds and fuses behind the microorganism.
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With regard to orthopaedic conditions such as arthritis, the paracrine factors of stem cell-based therapies appeared to be responsible for the majority of regenerative effects. Extracellular vesicles have a prominent role in the development of joints and in the regulation of the intra-articular homeostasis. In the case of arthritis, this homeostasis is disrupted due to different reasons. Hypothetically, one reason may be related to the accumulation of senescent cells and their associated secretory phenotype.
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The Vero cell lineage is continuous and aneuploid, meaning that it has an abnormal number of chromosomes. A continuous cell lineage can be replicated through many cycles of division and not become senescent. Vero cells are interferon-deficient; unlike normal mammalian cells, they do not secrete interferon alpha or beta when infected by viruses. However, they still have the Interferon-alpha/beta receptor, so they respond normally when recombinant interferon is added to their culture media.
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Certain Peltodoris individuals will undergo autotomy of the mantle margin before death. During this process, most of the mantle is lost except small parts around the gills and head. Most slugs die right after autotomization, a small number are able to survive for a few hours after autotomization but only for maximum 2-3 hours. Unlike in many other animals, autotomy in Peltodoris is not reversible and is not used for defense, but merely a senescent process.
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Surfactant is synthesised by type II alveolar cells and is made of a complex of phospholipids, proteins and saccharides. It functions to lower surface tension (to allow for lung expansion during inspiration), stabilise alveoli at the end of expiration (to prevent alveolar collapse) and prevents lung oedema. Surfactant also contributes to lung protection and defence as it is also an anti-inflammatory agent. Surfactant enhances the removal of inhaled particles and senescent cells away from the alveolar structure.
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The disease, gray mold, affects more than 200 dicotyledonous plant species and a few monocotyledonous plants found in temperate and subtropical regions. Serious economic losses can be a result of this disease to both field and greenhouse grown crops. The causal agent, Botrytis cinerea can infect mature or senescent tissues, plants prior to harvest, or seedlings. There is a wide variety of hosts infected by this pathogen including protein crops, fiber crops, oil crops, and horticultural crops.
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Méma is a region in Mali, Africa. A plain of alluvial deposits, it is situated north of Massina; west of Lake Debo and the Inner Niger Delta; and southwest of the Lakes Region. The now-senescent basin may have been the first settlement area for communities who migrated from distressed homelands of the Sahara during the last two millennia BC. Historically, Mema was one of the smaller Soninke states; it was also at one time a province of Ghana Empire.
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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).
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As is the case with all leeches, B. weberi is a hermaphrodite; sperm is passed from one individual to another by traumatic insemination. The eggs are fertilised and a cocoon is secreted by the clitellum and receives the from one to five eggs as it passes over the female gonopore. The eggs hatch in about one month and the juvenile leeches that emerge become mature in about four months. The adult can produce weekly cocoons for about three months before becoming senescent.
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Bacteriocyte tissue grows considerably during nymphal and larval development as it organizes into two regular clusters near the gut and developing embryonic chains. As some insects grow older, such as aphids, they begin to exhibit disorganized architecture in the bacteriocyte tissue. Eventually, this trend leads to progressive dis-aggregation of the tissue caused by an increasing lack of intercellular adhesion of the cells that only increases as the insect ages. Dis-aggregation appears prominently in reproductively active as well as senescent adults.
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His research has involved genetic approaches to elucidate the pathobiology of aging and age-related diseases. Important highlights include the discovery of the genetic defect causing Werner syndrome and certain familial forms of Alzheimer's disease. Martin also led research leading to the first evidence that cells from arteries, especially from parts that develop severe atherosclerosis, have limited potential to divide. He and colleagues also demonstrated that senescent cells cannot be "rescued" when their cytoplasm is mixed with cytoplasm from a normal young cell.
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The forest has not suffered from serious natural disturbances such as fires, wind storms or insect infestations for a very long time. The balsam fir (Abies balsamea) trees of the forest have never been disturbed by human activities, although a few northern white-cedar (Thuja occidentalis) have been cut. The forest stands are at least 270 to 290 years old, and have been able to evolve naturally. There are senescent trees and much wood debris in different stages of decomposition.
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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.
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Tetraphis pellucida develops a low-density asexual colony on a bare substrate, and is very susceptible to being out competed by species it commonly occurs with. Sexual colonies are much more likely to be disturbed than asexual colonies. Without disturbance Tetraphis pellucida has a very low probability of reestablishing where senescent or competitor colonies are. This is shown in the fact that Tetraphis pellucida is the dominant species in gaps of bryophyte communities on logs, whereas they are a minor component in an undisturbed community.
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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.
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First experimental result shows a possible high efficiency in partial rejuvenation of senescent mouse cells. Notably PCL rejuvenates exclusively one single tissue or organ, in contrast to classical cloning PCL is therefore unable to reconstitute an entire organism. Furthermore, PCL is feasible in a few hours in opposition to classical cloning or induced pluripotent stem cells (iPS) which all need weeks or months. Classical cloning can rejuvenate old cells but the process demands that the old cells must artificially pass through an embryonic cell stage.
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This has allowed massive stands of balsam fire to become established and to grow to their high proportion of the forest trees. The mature old-growth forest includes very old, senescent trees and the greatly decomposed debris of tree trunks as large as any now living. Renewal occurs when small gaps are created by the fall of isolated trees or small groups of trees. The spruce and fir are roughly equal in numbers, and there are also some white spruce (Picea glauca) and paper birch (Betula papyrifera).
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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.
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During mating, the male Macroctopus maorum will be on top pinning down the female and usually overpowering the female physically or pouncing on them. The male will inserts a sperm packet by passing it along the arms to the oviduct of the female. When it get near to the oviduct, the end of the spermatophore burst open and released the sperm.. Mather, J. A., Anderson, R. C. & Wood, J.B. (2010) Octopus: The Ocean’s Intelligent Invertebrate. Timber Press Male octopus will then become senescent and die after mating.
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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.
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The Window, 1983, Pencil, Aquarell on Paper, 13 x 18,5 cm Elmar Peintner rose to popularity at the beginning of the 1980s. He was a contemporary artist best known for his “Menschenbilder” (senescent children pictures), usually executed with hard pencils and additional water- colour, the models being from the family circle, the neighbourhood, or local rest homes. In the forefront, as with all his work, is not the naturalistic reproduction of nature, but the attempt to penetrate to the physical and mental structure of man via realism of microstructures.
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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.
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Stercobilin results from breakdown of the heme moiety of hemoglobin found in erythrocytes. Macrophages break down senescent erythrocytes and break the heme down into biliverdin, which rapidly reduces to free bilirubin. Bilirubin binds tightly to plasma proteins (especially albumin) in the blood stream and is transported to the liver, where it is conjugated with one or two glucuronic acid residues into bilirubin diglucuronide, and secreted into the small intestine as bile. In the small intestine, some bilirubin glucuronide is converted back to bilirubin via bacterial enzymes in the terminal ileum.
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It removes old red blood cells and holds a reserve of blood, which can be valuable in case of hemorrhagic shock, and also recycles iron. As a part of the mononuclear phagocyte system, it metabolizes hemoglobin removed from senescent red blood cells (erythrocytes). The globin portion of hemoglobin is degraded to its constitutive amino acids, and the heme portion is metabolized to bilirubin, which is removed in the liver. The spleen synthesizes antibodies in its white pulp and removes antibody-coated bacteria and antibody-coated blood cells by way of blood and lymph node circulation.
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Soszka and Kuczyńska described the appearance of morphological variations of Lactobacilli, when grown in the presence of a high concentration of Trichomonas vaginalis. The authors interpreted the observed atypical (coccoid) cell morphology as an involution (senescent, dying) form. Goisis et al. have shown, that shortened and coccoidal lactobacilli are not only present in the primary secretion samples of trichomoniasis patients, but also in the cultures started from these samples, free from competitive microorganisms and under optimal culture conditions, suggesting that the coccoid bacteria may represent a distinct viable phenotype.
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TEP abundance tends to be higher in coastal, shallow waters compared to deeper, oceanic waters. Diatom-dominated phytoplankton colonies produce larger, and stickier, TEPs, which may indicate that TEP size distribution and composition may be a useful tool in determining aggregate planktonic community structure. TEPs are formed from cell surface mucus sloughing, the disintegration of bacterial colonies, and precursors released by growing or senescent phytoplankton. TEP precursors can be fibrillar, forming larger colloids, or aggregations, and within hours to days after release from the cell are fully formed transparent exopolymer particles.
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The oldest part of the blade becomes senescent and sloughs off. The amphipod does not occupy the nest continuously but sometimes moves elsewhere on the host kelp, leaving a small grazing scar to show where it has foraged. Sometimes the nest is abandoned and a new nest may be built in a different location. Researchers studying this amphipod (Cerda, Hinojosa & Thiel, 2012) hypothesised that the position chosen for the nest might be a location where the maximum nutritional value of the tissue coincided with a decrease in production of defensive chemicals by the alga.
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The microbial loop is a trophic pathway in the marine microbial food web. The term "microbial loop" was coined by Azam et al. (1983) to describe the role played by microbes in the marine ecosystem carbon and nutrient cycles where dissolved organic carbon (DOC) is returned to higher trophic levels via the incorporation into bacterial biomass, and also coupled with the classic food chain formed by phytoplankton-zooplankton-nekton. At the end of phytoplankton bloom, when the algae enter a senescent stage, there is an accumulation of phytodetritus and an increased release of dissolved metabolites.
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Three G0 states exist and can be categorized as either reversible (quiescent) or irreversible (senescent and differentiated). Each of these three states can be entered from the G1 phase before the cell commits to the next round of the cell cycle. Quiescence refers to a reversible G0 state where subpopulations of cells reside in a 'quiescent' state before entering the cell cycle after activation in response to extrinsic signals. Quiescent cells are often identified by low RNA content, lack of cell proliferation markers, and increased label retention indicating low cell turnover.
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Apoptosis is a form of programmed cell death that is used by the body to remove unwanted, damaged, or senescent cells from tissues. Removal of apoptotic cells is carried out via phagocytosis by white blood cells such as macrophages and dendritic cells. Phagocytic white blood cells recognize apoptotic cells by their exposure of negatively charged phospholipids (phosphatidylserine) on the cell surface. In normal cells, the negative phospholipids reside on the inner side of the cellular membrane while the outer surface of the membrane is occupied by uncharged phospholipids.
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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.
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Recent study has identified Caveolin-1 as a potential regulator of TLR5 expression. In contrast to the decreased TLR4 level in senescent cells, TLR5 expression maintains relative stable during the aging process, which is correlated with the high level of Caveolin-1 in aging cells. Data from Caveolin-1 knockout mice demonstrated that TLR5 expression significantly decreases in the absence of Caveolin-1 expression in aging cells. It is hypothesized that the Caveolin-1 directly interacts with TLR5 to stabilize it and hence increases the level of TLR5.
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Once activated, they phosphorylate inositol lipids in the cell membrane, which triggers additional downstream signaling events. A variant of PASLI disease can all be caused by heterozygous splice site mutation in PIK3R1, which encodes the p85α, p55α, and p50α regulatory PI3K subunits. These patients suffer from recurrent sinopulmonary infections and lymphoproliferation, exhibit hyperactive PI3K signaling, and have prominent expansion and skewing of peripheral blood CD8+ T cells toward terminally differentiated, senescent effector cells with short telomeres. Figure 1: p110δ protein domains; vertical red lines indicate positions of substitution mutations.
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Study of the reported cases indicate that most adrenocortical adenomas occur due to neoplastic proliferation of adrenal cortical cells within the three distinct layers of adrenal cortex. In humans, the adrenal cortex comprises three concentric zones including the zona glomerulosa, zona fasciculata, and zona reticularis that under normal conditions respond to body's physiological demands for steroid hormones. The adrenal cortex is considered a dynamic organ in which senescent cells are replaced by newly differentiated cells. This constant renewal facilitates organ remodeling which contributes to dynamic characteristics of the adrenal cortex.
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NKG2D ligands are induced-self proteins which are completely absent or present only at low levels on surface of normal cells, but they are overexpressed by infected, transformed, senescent and stressed cells. Their expression is regulated at different stages (transcription, mRNA and protein stabilization, cleavage from the cell surface) by various stress pathways. Among them, one of the most prominent stress pathways is DNA damage response. Genotoxic stress, stalled DNA replication, poorly regulated cell proliferation in tumorigenesis, viral replication or some viral products activate the ATM and ATR kinases.
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Mating Love dart of Cepaea nemoralis This is a very common and widespread species in Western Europe, occupying a very wide range of habitats from dunes along the coastline, to woodlands with full canopy cover. It lives in shrubs and open woods, in plains and highlands, dunes, cultivated habitats, gardens and roadsides. It can be found up to an altitude of 1200 m in the Alps, 1800 m in the Pyrenees, 900 m in Wales, 600 m in Scotland. This species feeds mainly on dead or senescent plants.
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Fire suppression has led to slow population declines over the last century by altering the health and composition dynamics of stands without the fire ecology balancing their habitat and suppressing insect-disease threats. In the absence of low-level wildfire cycles, whitebark pines in these stands are replaced by more shade-tolerant, fire-intolerant species such as subalpine fir (Abies lasiocarpa) and Engelmann spruce (Picea engelmannii). In addition, senescent and blister rust-infected pine trees are not destroyed by natural periodic ground fires, further diminishing the whitebark pine forest's vitality and survival.
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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.
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The Lac- Auger Old Forest mainly consists of stands of black spruce (Picea mariana) and balsam fir (Abies balsamea), or stands of black spruce alone, over 200 years old. The oldest trees are about 285 years old. The forest has not been seriously affected by fire, insect infestations or windstorms, and has never been modified by human activities. It has developed naturally, and has trees of varied ages from saplings to mature and senescent trees of great age, with much wood litter including the fallen trunks of large trees.
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Senescent cells undergo chromatin landscape modifications as constitutive heterochromatin migrates to the center of the nucleus and displaces euchromatin and facultative heterochromatin to regions at the edge of the nucleus. This disrupts chromatin-lamin interactions and inverts of the pattern typically seen in a mitotically active cell. Individual Lamin-Associated Domains (LADs) and Topologically Associating Domains (TADs) are disrupted by this migration which can affect cis interactions across the genome. Additionally, there is a general pattern of canonical histone loss, particularly in terms of the nucleosome histones H3 and H4 and the linker histone H1.
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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.
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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.
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The Methuselah Fund was created as an LLC subsidiary of the Methuselah Foundation to incubate and invest in early-stage companies. Investments to date have included: Organovo (NYSE: ONVO), a leader in 3D bioprinting; Silverstone Solutions (acquired by BiologicTx in 2013), a maker of kidney- matching software that enables hospitals and transplant organizations to more quickly and accurately pair patients with compatible donors; Oisin Biotechnologies, a company aiming to remove senescent cells, commonly seen as a hallmark of aging; and Leucadia Therapeutics, a company working to address Alzheimer's disease by restoring the flow of cerebrospinal fluid across the cribriform plate.
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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.
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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.
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Although the album received generally favorable reviews, some critics found the album's quiet atmosphere "underwhelming." Others criticized the band for a perceived lack of invention. When asked about the album's quiet nature, Kaplan stated, Battery Park, New York City, July 4, 2005 Yo La Tengo collaborated with Yoko Ono on the 2003 charity album Wig in a Box: Songs from and Inspired by Hedwig and the Angry Inch in support of the Harvey Milk High School. The band put together their first "best of" compilation entitled Prisoners of Love: A Smattering of Scintillating Senescent Songs: 1985–2003 which was released in 2005.
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MBL belongs to the class of collectins in the C-type lectin superfamily, whose function appears to be pattern recognition in the first line of defense in the pre-immune host. MBL recognizes carbohydrate patterns, found on the surface of a large number of pathogenic micro-organisms, including bacteria, viruses, protozoa and fungi. Binding of MBL to a micro- organism results in activation of the lectin pathway of the complement system. Another important function of MBL is that this molecule binds senescent and apoptotic cells and enhances engulfment of whole, intact apoptotic cells, as well as cell debris by phagocytes.
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Octopus bush is used in many Pacific islands as a traditional medicine to treat ciguatera fish poisoning, which is caused by powerful ciguatoxins produced by microscopic Gambierdiscus algae. Scientists from the Institute of Research for Development (IRD) and the Louis Malarde Institute in French Polynesia and Pasteur Institute in New Caledonia are researching the plant chemistry and believe that senescent leaves contain rosmarinic acid and derivatives, which are known for its antiviral, antibacterial, antioxidant, and anti-inflammatory properties. The researchers think that rosmarinic acid removes the ciguatoxins from their sites of action, as well as being an anti- inflammatory agent.
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Senescent leaves with early blight infections and leaves with flea beetle injury are especially important spore sources because the fungus can colonize and produce new spores in these wounded areas. The growth of C. coccodes is most rapid at 80 °F, although the fungus can cause infections over a wide range of temperatures between 55°–95 °F. Wet weather promotes disease development, and splashing water in the form of rain or irrigation favors the spread of the disease (Dillard, 1987). The pathogen also produces an acervulus which is full of conidia that help to spread the infection (Hughes, 2009).
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A vital part of erythropoesis is the clustering of erythroblasts around bone marrow macrophages to form erythroblastic islands. The erythroblast is then able to remove its nucleus, which is in turn ingested and broken down by the macrophages, to become a mature erythrocyte. During this process ICAM-4 binds to VLA-4, an erythroblast binding site, on adjacent erythroblasts and to αv integrins on macrophages to help stabilise the erythroblastic islands. The binding of red cells to macrophages in the spleen by ICAM-4 could also play a part in the removal of senescent red cells.
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A forest in old-growth stage has a mix of tree ages, due to a distinct regeneration pattern for this stage. New trees regenerate at different times from each other, because each of them has different spatial location relative to the main canopy, hence each one receives a different amount of light. The mixed age of the forest is an important criterion in ensuring that the forest is a relatively stable ecosystem in the long term. A climax stand that is uniformly aged becomes senescent and degrades within a relatively short time to result in a new cycle of forest succession.
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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.
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Primary cell culture is the ex vivo culture of cells freshly obtained from a multicellular organism, as opposed to the culture of immortalized cell lines. In general, primary cell cultures are considered more representative of in vivo tissues than cell lines, and this is recognized legally in some countries such as the UK (Human Tissue Act 2004). However, primary cells require adequate substrate and nutrient conditions to thrive and after a certain number of divisions they acquire a senescent phenotype, leading to irreversible cell cycle arrest. The generation of cell lines stems from these two reasons.
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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.
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PCL consists in introducing a somatic adult or senescent cell nucleus or entire cell with enlarged membrane pores in an (activated) oocyte and to withdraw this treated cell before its de-differentiation and first cell division occurs. Thus, the progressive rejuvenation capability of the oocyte is used only temporarily in order to obtain a partial natural rejuvenation. PCL permits to envisage a chosen degree of partial rejuvenation in changing the duration of the introduction of the treated cell in the oocyte. Using PCL cell de- differentiation and its age reprogramming might be, at least partially, separable.
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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.
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As the colony develops and resources become depleted, stressed cells can form cilia on all surfaces, including a basal wreath of cilia, mature into macrozooids, and will detach from the stalk and swim away. Colonies may become large, as the macrozooids may not have to travel far to find additional substrate. The initial colony will eventually enter into a senescent phase, where it will slow or even stop its biological functions of replication and release of swarmer cells. At this point microzooids will begin to die from the bottom of the stalk progressing to the top.
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Cancerous cells overexpress a number of proteins, including growth factor receptors, such as EGFR, or signal transduction proteins such as PI3K and AKT (Inhibition of these proteins may trigger apoptosis). Hsp90 stabilizes various growth factor receptors and some signaling molecules including PI3K and AKT proteins. Hence inhibition of Hsp90 downregulates the PI3K/AKT pathway leading to downregulation of the anti-apoptotic protein Bcl-w resulting in apoptosis of cancerous and senescent cells. Another important role of Hsp90 in cancer is the stabilization of mutant proteins such as v-Src, the fusion oncogene Bcr/Abl, and mutant forms of p53 that appear during cell transformation.
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Scrubland of the Sierra Pelona Mountains, Southern California Fire, both natural and human-caused, has played a large role in shaping the ecology of Mediterranean ecoregions. The hot, dry summers make much of the region prone to fires, and lightning-caused fires occur with some frequency. Many of the plants are pyrophytes, or fire-loving, adapted or even depending on fire for reproduction, recycling of nutrients, and the removal of dead or senescent vegetation. In both the Australian and Californian Mediterranean-climate eco-regions, native peoples used fire extensively to clear brush and trees, making way for the grasses and herbaceous vegetation that supported game animals and useful plants.
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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.
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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.
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The tests further confirmed that MK specifically increased chemotherapeutic resistance in the transfected WT-MK cells versus regular WT cells, confirming the specific chemoresistant properties of MK. In addition, the mechanism for such anti-apoptotic (anti-cell death) activity was studied, specifically using the chemotherapeutic Doxorubicin (Adriamycin) on osteosarcoma (Saos2) cells. Doxorubicin works by putting rampant cancer cells into a senescent state. MK, in WT-MK transfected cells versus WT cells, seemed to activate PKB (Akt), mTOR, and Bad protein, while it inactivated caspase-3. PKB, mTOR, and Bad are all elements associated with the cell cycle survival pathway, whereas caspase-3 is important in the apoptotic pathway (cell death).
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On Guam, the Mariana crow's decline is primarily due to predation by the introduced brown tree snake (Boiga irregularis). In spite of protection of nesting-sites by electrical tree barriers, the remaining birds are considered to be reproductively senescent. On Rota, many other threats endanger the crow, including homestead development, resort and golf-course construction, agricultural settlement, nest-predation from introduced rats, the mangrove monitor lizard (Varanus indicus), typhoons, predation from feral cats, disease, and competition with the black drongo (Dicrurus macrocercus). More recently, the brown tree snake has also been detected on Rota, likely leading to serious declines in the Mariana crow population there if the snake population establishes itself.
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A consequence of histone loss in yeast is the amplification of transcription. In younger cells, genes that are most induced with age have specific chromatin structures, such as fuzzy nuclear positioning, lack of a nuclesome depleted region (NDR) at the promoter, weak chromatin phasing, a higher frequency of TATA elements, and higher occupancy of repressive chromatin factors. In older cells, however, the same genes nucleosome loss at the promoter is more prevalent which leads to higher transcription of these genes. This phenomenon is not only seen in yeast, but has also been seen in aging worms, during aging of human diploid primary fibroblasts, and in senescent human cells.
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They propose that the protruding of a flat spot is a result of the death of aged cells in the spot and release of lipofuscin bodies. The aggregating cells would form a capsule, and the dense lipofuscin bodies make the protruding spot soft and dark in color. However, this proposal appeared as a preprint in 2015, has little direct empirical support, and has never been published in a peer reviewed journal. Another group has reported that "age spots" taken from human skin biopsies of patients facial senile lentigo of Fitzpatrick skin type III or IV aged 55-62 are enriched with senescent fibroblasts compared to surrounding skin.
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The ship's main computer has also been damaged, so its decision to have the captain replaced by one of the passengers to maximize survival causes disagreement. The damage to the ship prevents it traveling faster than light, and the passengers and crew debate using the ship's remaining sub-light engine to travel relativistically to a neighboring star to look for a more viable planet. Reluctantly, believing that any other similarly senescent star will offer no better option, the people accede to the new captain's order to land on Earth despite the lack of an atmosphere. However, this is not a haphazard decision by the new captain, who is an astrophysicist.
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Most species grow quickly, mature early, and are short-lived. In most species, the male uses a specially adapted arm to deliver a bundle of sperm directly into the female's mantle cavity, after which he becomes senescent and dies, while the female deposits fertilised eggs in a den and cares for them until they hatch, after which she also dies. Strategies to defend themselves against predators include the expulsion of ink, the use of camouflage and threat displays, the ability to jet quickly through the water and hide, and even deceit. All octopuses are venomous, but only the blue-ringed octopuses are known to be deadly to humans.
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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).
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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.
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Telomerase reverse transcriptase (abbreviated to TERT, or hTERT in humans) is a catalytic subunit of the enzyme telomerase, which, together with the telomerase RNA component (TERC), comprises the most important unit of the telomerase complex. Telomerases are part of a distinct subgroup of RNA- dependent polymerases. Telomerase lengthens telomeres in DNA strands, thereby allowing senescent cells that would otherwise become postmitotic and undergo apoptosis to exceed the Hayflick limit and become potentially immortal, as is often the case with cancerous cells. To be specific, TERT is responsible for catalyzing the addition of nucleotides in a TTAGGG sequence to the ends of a chromosome's telomeres.
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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.
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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.
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The tennis courts (or at least their sites) have a moderate degree of historical and social significance, demonstrating a form of recreation favoured by landowners and schools for gentlefolk for the first three to four decades of the 20th century. They carry the potential to be restored to their former use. The trees on the site have varying degrees of significance, depending on their age and with which phase of ownership they were associated. Those of greater historical and aesthetic significance are the senescent Pine, old Camphor Laurel and a few old Pepper Trees originally planted () just beyond the south- west sector of the drive, and the mature Bunya Pine at the entrance to the House grounds.
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Rejuvenation Research. September 2007, 10(3): 359-366. doi:10.1089/rej.2007.0594. Methuselah has also provided funding and strategic support to companies developing breakthrough technologies and clinical interventions in regenerative medicine. These companies include: Organovo (NYSE: ONVO), a pioneer in 3D tissue printing; Silverstone Solutions (acquired by BiologicTx in 2013), a maker of kidney-matching software that has enabled hospitals and transplant organizations to more quickly and accurately pair patients with compatible donors; Oisin Biotechnologies, a creator of an intervention to remove harmful senescent cells ("zombie" cells) based on their DNA expression; and Leucadia Therapeutics, a company developing a therapy to address Alzheimer's disease by restoring the flow of cerebrospinal fluid across the cribriform plate in the nasal cavity.
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As the vine progresses through the ripening stage, malic acid is metabolized in the process of respiration, and by harvest, its concentration could be as low as 1 to 9 g/l. The respiratory loss of malic acid is more pronounced in warmer climates. When all the malic acid is used up in the grape, it is considered “over-ripe” or senescent. Winemakers must compensate for this loss by adding extraneous acid at the winery in a process known as acidification.J. Robinson (ed) “The Oxford Companion to Wine” Third Edition pg 421–422 Oxford University Press 2006 Malic acid can be further reduced during the winemaking process through malolactic fermentation or MLF.
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Ashwell’s goal as a researcher was to devise a labeling serum glycoproteins in order to study the role of ceruloplasmin in Wilson disease. With another researcher named Anatol G. Morell, he worked to propose that membrane lectins remove senescent circulating glycoproteins, and discovered one of the earliest known carbohydrate receptors. They were able to devise a labeling procedure which allowed them to remove enzymes of the glycoproteins' sialic acid residue. By completing this process, they were able to incorporate other substances into the protein. In 1974, Ashwell and Morell happened to discover that a certain receptor in a human’s liver is able to recognize a specific glycoprotein called asialoglycoprotein.“Gilbert Ashwell: Sweet on Science.” Nature Medicine. 2008. Web. 11 March 2010.
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Much discussion has involved whether or not ivy climbing trees will harm them. In Europe, the harm is generally minor although there can be competition for soil nutrients, light, and water, and senescent trees supporting heavy ivy growth can be liable to windthrow damage. The UK's Woodland Trust says "Ivy has long been accused of strangling trees, but it doesn’t harm the tree at all, and even supports at least 50 species of wildlife." Harm and problems are more significant in North America, where ivy is without the natural pests and diseases that control its vigour in its native continents; the photosynthesis or structural strength of a tree can be overwhelmed by aggressive ivy growth leading to death directly or by opportunistic disease and insect attacks.
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This indicates that MK caused the cells to initiate the survival pathway (via PKB, mTOR, and Bad activation) and inhibit the senescent or apoptotic pathway (via inhibiting caspase-3) encouraging the chemoresistance seen in resistant cells and in the co-culture experiments. The activation and inhibition of these particular factors clearly is maintaining the immortal quality inherent in cancer cells and specifically in the resistant cell types. Stat-3, however, which is another survival pathway factor, does not appear to have any change in activation between the wild type cells and the MK-transfected WT cells, as was initially believed from a previous study. MK may potentially be indirectly targeted as a cancer treatment as a result of its cancerous proliferation properties.
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There are two assumptions relating to California chaparral fire regimes that appear to have caused considerable debate, and sometimes confusion and controversy, within the fields of wildfire ecology and land management. # That older stands of chaparral become "senescent" or "decadent", thus implying that fire is necessary for the plants to remain healthy, # That wildfire suppression policies have allowed dead chaparral to accumulate unnaturally, creating ample fuel for large fires. The perspective that older chaparral is unhealthy or unproductive may have originated during the 1940s when studies were conducted measuring the amount of forage available to deer populations in chaparral stands. However, according to recent studies, California chaparral is extraordinarily resilient to very long periods without fire and continues to maintain productive growth throughout pre-fire conditions.
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Thermophilic fungi are primarily compost fungi, though T. lanuginosus has also been found to thrive in spoil tips, senescent grass leaves, sewage, and peat and bog soils, and is the dominant species of thermophilic fungi in hot springs. Though it is sometimes found in soil, this is not a natural habitat for T. lanuginosus, and the concentration of spores of thermophilic fungi per gram material is approximately 106 higher in composts than soils. It is proposed that their wide presence in soil is due to dispersal of spores elsewhere and fallout from air. T. lanuginosus has two of the most important qualities required for being a compost colonizer - it is able to withstand high temperatures and use complex carbon sources for energy.
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Many fishermen generally release dusky flatead over 70 cm, believing that they are important large breeding females. The hypothesis that dusky flathead over 70 cm are "important large breeding females" is questionable. A study by Pollock (2014) shows that the vast majority of eggs produced by the annual spawning aggregation come from the mid-size females (50 cm–60 cm), but more importantly the large females over 70 cm are often reproductively senescent—that is they have degenerate ovaries in which the eggs are breaking down or have broken down, and are not shed. A study is currently underway in northern New South Wales which is finding at most of the large female flathead (>75 cm) also have degenerate ovaries during the early spawning period (Nov/Dec), whereas the mid-size females have healthy ovaries with developing yolky eggs.
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Over the course of a pregnancy, PAI-2 plasma concentration rises from nearly- undetectable levels to 250 ng/mL (mostly in glycosylated form). Among immune cells, macrophages are the main producers of PAI-2, as both B-cells and T-cells do not produce significant amounts. PAI-2 plays a role in inflammatory responses and infections, potentially in downregulating T cells that secrete IgG2c and interferon type II. Due to its position on chromosome 18 close to the bcl-2 protooncogene and several other serpins, PAI-2's role in apoptosis has been investigated, but current evidence remains inconclusive. A recent study suggests PAI-2 may be a direct downstream target and activator of p53, and may directly stabilize p21; in addition, PAI-2 expression is increased in senescent fibroblasts and may arrest growth of young fibroplasts.
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Exposure to an enriched environment, defined as a combination of more opportunities for physical activity, learning and social interaction, may produce structural and functional changes in the brain and influence the rate of neurogenesis in adult and senescent animal model hippocampi. Many of these changes can be effected merely by introducing a physical exercise regimen rather than requiring cognitive activity per se. In humans, the posterior hippocampi of licensed London taxi drivers was famously found to be larger than that of matched controls, while the anterior hippocampi were smaller. This study shows that people choosing taxi driving as a career (one which has as a barrier to entry—the ability to memorize London's streets—described as "the world's most demanding test (of street knowledge)") have larger hippocampi, but does not demonstrate change in volume as a result of driving.
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"In claims similar to those in the Qur'an, Donovan Joyce's The Jesus Scroll unveiled 'Jesus the Senescent Savior', who survived Golgotha and lived to the ripe old age of eighty." Joyce's book made the claim that Jesus of Nazareth may have actually died aged 80 at Masada "Smith's cheek [in The Secret Gospel] seems modest, however, compared to the sheer gall of Australian Donovan Joyce, creator of a preposterous pseudo-study called The Jesus Scroll (Dial Press; $5.95). In Donovan's account Jesus does not expire on the cross but marries Mary Magdalene and dies at 80, "the last Hasmonean king of Israel," defended by loyal Zealots at Masada." near the Dead Sea, site of the last stand made by Jewish zealot rebels against the Roman Empire, after the Fall of Jerusalem and the destruction of the Second Temple. Joyce, an Australian journalist, claimed to have seen a scroll stolen from the Masada excavations.
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There were reports from nurseryman David Boyle and others of trees in the Yarra Valley, Otways and Dandenong Ranges reaching "half a thousand feet". Edward Snell, civil engineer and surveyor, made one of the earliest reports of hundreds of trees at least 120 metres (400 feet) tall on an overland trip across the Otways Ranges from Forrest to Apollo Bay in 1856. The tallest reliably measured tree in Victoria was a mountain ash near Thorpdale which in 1881 was measured by a government surveyor, George Cornthwaite, and his brother Bill, a farmer, at 114.3 metres (375 feet) after it was cut down to make fence palings. Modern Lidar imagery of the forests is being used to find remaining stands of tall trees. The tallest regrowth mountain ash in Victoria is currently named Artemis which can be found near Beenak at 302 feet (92.1 m) while the Ada Tree at 72 metres (236 feet) is thought to be between 350 and 450 years old, but with a senescent crown and is a popular tourist destination in State forest east of Powelltown.
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ABT-737 is a small molecule drug that inhibits Bcl-2 and Bcl-xL, two members of the Bcl-2 family of evolutionarily-conserved proteins that share Bcl-2 Homology (BH) domains. First developed as a potential cancer chemotherapy, it was subsequently identified as a senolytic (a drug that selectively induces cell death in senescent cells). The Bcl-2 family is most notable for their regulation of apoptosis, a form of programmed cell death, at the mitochondrion; Bcl-2 and Bcl-xL are anti-apoptotic proteins. Because many cancers have mutations in these genes that allow them to survive, scientists began working to develop drugs that would inhibit this pathway in the 1990s. ABT-737 was one of the earliest of a series of drugs developed by Abbott Laboratories (now Abbvie) to target this pathway, based on their resolution of the 3D structure of Bcl-xL and studies using high-field solution nuclear magnetic resonance (NMR) that revealed how the BH domains of these proteins interacted with their targets.
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