Updated 04-May-2020.
Mondo shtuff from around the internet, all about SENESCENCE!
<img src='https://ui.adsabs.harvard.edu/styles/img/transparent_logo.svg' alt='Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders”>Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders: Advanced age is the main risk factor for most chronic diseases and functional deficits in humans, but the fundamental mechanisms that drive ageing remain largely unknown, impeding the development of interventions that might delay or prevent age-related disorders and maximize healthy lifespan. Cellular senescence, which halts the proliferation of damaged or dysfunctional cells, is an important mechanism to constrain the malignant progression of tumour cells. Senescent cells accumulate in various tissues and organs with ageing and have been hypothesized to disrupt tissue structure and function because of the components they secrete. However, whether senescent cells are causally implicated in age-related dysfunction and whether their removal is beneficial has remained unknown. To address these fundamental questions, we made use of a biomarker for senescence, p16Ink4a, to design a novel transgene, INK-ATTAC, for inducible elimination of p16Ink4a-positive senescent cells upon administration of a drug. Here we show that in the BubR1 progeroid mouse background, INK-ATTAC removes p16Ink4a-positive senescent cells upon drug treatment. In tissues–such as adipose tissue, skeletal muscle and eye–in which p16Ink4a contributes to the acquisition of age-related pathologies, life-long removal of p16Ink4a-expressing cells delayed onset of these phenotypes. Furthermore, late-life clearance attenuated progression of already established age-related disorders. These data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.
My botty best at summarizing from Wikipedia: calorie restriction can extend lifespan by 50% in rats . existence of species with negligible senescence and potentially immortal organisms such as Hydra . rare human mutations can cause accelerated aging diseases . overexposure to ultraviolet radiation accelerates skin aging . two organisms of the same species can age at different rates . gompertz–Makeham law of mortality says mortality rate increases exponentially with age . a group of scientists defined nine hallmarks of aging common between organisms . Aging is characterized by declining ability to respond to a mouse is elderly at 3 years, a human at 80 years, and gingko trees show little effect of age . there is negligible senescence in some groups, such as the genus Hydra the Turritopsis dohrnii, also known as the immortal jellyfish, is not biologically immortal . some species exhibit “negative senescence,” in which reproduction capability increases or is stable . mortality the dominant mutation that causes Huntington’s disease remained in the population . natural selection had not eliminated it . the onset of this neurological disease is invariably fatal within 10–20 years . the ‘real hazards of mortality’ such as predation, disease, and accidents, are known ‘extrinsic mortality’ a single gene may affect multiple traits. some traits that increase fitness early in life may also have negative effects later in life . because many more individuals are alive at young ages than at old ages, even small positive effects early can be strongly selected for . Williams suggests that the reproductive-cell cycle theory suggests aging is regulated by changes in hormonal signaling over the lifespan . the theory suggests that aging occurs due to a strategy in which an individual only invests in maintenance of the soma the cellular senescence theory of aging posits organismal aging is a consequence of the accumulation of less physiological useful senescent cells . ectopic expression of the embryonic transcription factor one lineage undergoes cellular senescence faster than the other . natural selection can remove damaged cells and prevent their proliferation . some cells mutate in ways that escape these control mechanisms . in about 85% of tumors, this evasion of cellular senescence is the result of up-activation of their telomerase genes . in culture, fibroblasts can reach a maximum of metabolic rate is a poor predictor of lifespan for birds, bats and other species . metabolic rate does not correlate with longevity in mammals or birds . senescent cells, and cancer, both lead to increasing rates of mortality damage to long-lived biopolymers, such as structural proteins or DNA, is in part responsible for aging . certain metal ions found in the body may participate in the process . damage can include breakage of bio people with diabetes, who have elevated blood sugar, develop senescence-associated disorders . sugar damage is linked to oxidant damage in a process termed glycoxidation . free radicals can damage proteins, chemical damage to structural proteins can lead to loss of function . damage to enzymes reduces cellular functionality . mitochondrial membrane reduces electric potential and ability to generate energy . the impact of alcohol on aging can be partly explained by alcohol’s activation of the HPA axis . graying of hair, skin wrinkles and other changes seen with aging are not better indicators of future functionality study of these organisms has revealed the presence of at least two conserved aging pathways . gene expression is imperfectly controlled, and it is possible that random fluctuations in the expression levels of many genes contribute to the aging process . Sufferers exhibit symptoms resembling accelerated aging, including wrinkled skin . the cause of Hutchinson–Gilford progeria syndrome was reported in the journal Nature in may 2003 . report suggests