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Senescence

February 28, 2023

This article is about the aging of whole organisms including animals. For aging specifically in humans, see Aging. For plants, see Plant senescence. For cells that stop dividing, see Cellular senescence. For bacteria, see Bacterial senescence.

Senescence (/sɪˈnɛsəns/) or biological aging is the gradual deterioration of functional characteristics in living organisms. The word senescence can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence involves an increase in death rates and/or a decrease in fecundity with increasing age, at least in the latter part of an organism's life cycle.

Supercentenarian Ann Pouder (8 April 1807 – 10 July 1917) photographed on her 110th birthday. A heavily lined face is common in human senescence.

Senescence is the inevitable fate of almost all multicellular organisms with germ-soma separation,[1][2] but it can be delayed. The discovery, in 1934, that calorie restriction can extend lifespan by 50% in rats, and the existence of species having negligible senescence and potentially immortal organisms such as Hydra, have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases.

Environmental factors may affect aging – for example, overexposure to ultraviolet radiation accelerates skin aging. Different parts of the body may age at different rates. Two organisms of the same species can also age at different rates, making biological aging and chronological aging distinct concepts.

Definition and characteristics

Organismal senescence is the aging of whole organisms. Actuarial senescence can be defined as an increase in mortality and/or a decrease in fecundity with age. The Gompertz–Makeham law of mortality says that the age-dependent component of the mortality rate increases exponentially with age.

Aging is characterized by the declining ability to respond to stress, increased homeostatic imbalance, and increased risk of aging-associated diseases including cancer and heart disease. Aging has been defined as "a progressive deterioration of physiological function, an intrinsic age-related process of loss of viability and increase in vulnerability."[3]

In 2013, a group of scientists defined nine hallmarks of aging that are common between organisms with emphasis on mammals:

The environment induces damage at various levels, e.g. damage to DNA, and damage to tissues and cells by oxygen radicals (widely known as free radicals), and some of this damage is not repaired and thus accumulates with time.[5] Cloning from somatic cells rather than germ cells may begin life with a higher initial load of damage. Dolly the sheep died young from a contagious lung disease, but data on an entire population of cloned individuals would be necessary to measure mortality rates and quantify aging.[citation needed]

The evolutionary theorist George Williams wrote, "It is remarkable that after a seemingly miraculous feat of morphogenesis, a complex metazoan should be unable to perform the much simpler task of merely maintaining what is already formed."[6]

Variation among species

Different speeds with which mortality increases with age correspond to different maximum life span among species. For example, a mouse is elderly at 3 years, a human is elderly at 80 years,[7] and ginkgo trees show little effect of age even at 667 years.[8]

Almost all organisms senesce, including bacteria which have asymmetries between "mother" and "daughter" cells upon cell division, with the mother cell experiencing aging, while the daughter is rejuvenated.[9][10] There is negligible senescence in some groups, such as the genus Hydra.[11] Planarian flatworms have "apparently limitless telomere regenerative capacity fueled by a population of highly proliferative adult stem cells."[12] These planarians are not biologically immortal, but rather their death rate slowly increases with age. Organisms that are thought to be biologically immortal would, in one instance, be the Turritopsis dohrnii, also known as the "immortal jellyfish", due to its ability to revert to its youth when it undergoes stress during adulthood.[13] The reproductive system is observed to remain intact, and even the gonads of the Turritopsis dohrnii are existing.[14]

Some species exhibit "negative senescence", in which reproduction capability increases or is stable, and mortality falls with age, resulting from the advantages of increased body size during aging.[15]

Theories of aging

More than 300 different theories have been posited to explain the nature and causes of aging.[16] A good theory would both explain past observations and predict the results of future experiments.

Theories of aging fall into two broad categories, evolutionary theories of aging and mechanistic theories of aging. Evolutionary theories of aging primarily explain why aging happens,[17] but do not concern themselves with the molecular mechanism(s) that drive the process. All evolutionary theories of aging rest on the basic mechanisms that the force of natural selection declines with age.[18][19] Mechanistic theories of aging can be divided into theories that propose aging is programmed, and damage accumulation theories, i.e. those that propose aging to be caused by specific molecular changes occurring over time.

Evolutionary aging theories

Main article: Evolution of ageing

Antagonistic pleiotropy

Main article: Antagonistic pleiotropy hypothesis

One theory was proposed by George C. Williams[6] and involves antagonistic pleiotropy. A single gene may affect multiple traits. Some traits that increase fitness early in life may also have negative effects later in life. But, because many more individuals are alive at young ages than at old ages, even small positive effects early can be strongly selected for, and large negative effects later may be very weakly selected against. Williams suggested the following example: Perhaps a gene codes for calcium deposition in bones, which promotes juvenile survival and will therefore be favored by natural selection; however, this same gene promotes calcium deposition in the arteries, causing negative atherosclerotic effects in old age. Thus, harmful biological changes in old age may result from selection for pleiotropic genes that are beneficial early in life but harmful later on. In this case, selection pressure is relatively high when Fisher's reproductive value is high and relatively low when Fisher's reproductive value is low.

Cancer versus cellular senescence tradeoff theory of aging

Main article: Immunosenescence

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.[2]

Disposable soma

Main article: Disposable soma theory of aging

The disposable soma theory of aging was proposed by Thomas Kirkwood in 1977.[1][20] The theory suggests that aging occurs due to a strategy in which an individual only invests in maintenance of the soma for as long as it has a realistic chance of survival.[21] A species that uses resources more efficiently will live longer, and therefore be able to pass on genetic information to the next generation. The demands of reproduction are high, so less effort is invested in repair and maintenance of somatic cells, compared to germline cells, in order to focus on reproduction and species survival.[22]

Programmed aging theories

Main article: Programmed ageing

Programmed theories of aging posit that aging is adaptive, normally invoking selection for evolvability or group selection.

The reproductive-cell cycle theory suggests that aging is regulated by changes in hormonal signaling over the lifespan.[23]

Only a very small minority of scientists believe aging to be programmed, and the vast majority believe aging is due to some kind of damage accumulation.[24]

Damage accumulation theories

The free radical theory of aging

Main article: Free-radical theory of aging

One of the most prominent theories of aging was first proposed by Harman in 1956.[25] It posits that free radicals produced by dissolved oxygen, radiation, cellular respiration and other sources cause damage to the molecular machines in the cell and gradually wear them down. This is also known as oxidative stress.

There is substantial evidence to back up this theory. Old animals have larger amounts of oxidized proteins, DNA and lipids than their younger counterparts.[26][27]

Chemical damage

 
Elderly Klamath woman photographed by Edward S. Curtis in 1924
See also: DNA damage theory of aging

One of the earliest aging theories was the Rate of Living Hypothesis described by Raymond Pearl in 1928[28] (based on earlier work by Max Rubner), which states that fast basal metabolic rate corresponds to short maximum life span.

While there may be some validity to the idea that for various types of specific damage detailed below that are by-products of metabolism, all other things being equal, a fast metabolism may reduce lifespan, in general this theory does not adequately explain the differences in lifespan either within, or between, species. Calorically restricted animals process as much, or more, calories per gram of body mass, as their ad libitum fed counterparts, yet exhibit substantially longer lifespans.[citation needed] Similarly, metabolic rate is a poor predictor of lifespan for birds, bats and other species that, it is presumed, have reduced mortality from predation, and therefore have evolved long lifespans even in the presence of very high metabolic rates.[29] In a 2007 analysis it was shown that, when modern statistical methods for correcting for the effects of body size and phylogeny are employed, metabolic rate does not correlate with longevity in mammals or birds.[30]

With respect to specific types of chemical damage caused by metabolism, it is suggested that damage to long-lived biopolymers, such as structural proteins or DNA, caused by ubiquitous chemical agents in the body such as oxygen and sugars, are in part responsible for aging. The damage can include breakage of biopolymer chains, cross-linking of biopolymers, or chemical attachment of unnatural substituents (haptens) to biopolymers.[citation needed] Under normal aerobic conditions, approximately 4% of the oxygen metabolized by mitochondria is converted to superoxide ion, which can subsequently be converted to hydrogen peroxide, hydroxyl radical and eventually other reactive species including other peroxides and singlet oxygen, which can, in turn, generate free radicals capable of damaging structural proteins and DNA.[5] Certain metal ions found in the body, such as copper and iron, may participate in the process. (In Wilson's disease, a hereditary defect that causes the body to retain copper, some of the symptoms resemble accelerated senescence.) These processes termed oxidative stress are linked to the potential benefits of dietary polyphenol antioxidants, for example in coffee,[31] red wine and tea.[32]

Sugars such as glucose and fructose can react with certain amino acids such as lysine and arginine and certain DNA bases such as guanine to produce sugar adducts, in a process called glycation. These adducts can further rearrange to form reactive species, which can then cross-link the structural proteins or DNA to similar biopolymers or other biomolecules such as non-structural proteins. People with diabetes, who have elevated blood sugar, develop senescence-associated disorders much earlier than the general population, but can delay such disorders by rigorous control of their blood sugar levels. There is evidence that sugar damage is linked to oxidant damage in a process termed glycoxidation.

Free radicals can damage proteins, lipids or DNA. Glycation mainly damages proteins. Damaged proteins and lipids accumulate in lysosomes as lipofuscin. Chemical damage to structural proteins can lead to loss of function; for example, damage to collagen of blood vessel walls can lead to vessel-wall stiffness and, thus, hypertension, and vessel wall thickening and reactive tissue formation (atherosclerosis); similar processes in the kidney can lead to kidney failure. Damage to enzymes reduces cellular functionality. Lipid peroxidation of the inner mitochondrial membrane reduces the electric potential and the ability to generate energy. It is probably no accident that nearly all of the so-called "accelerated aging diseases" are due to defective DNA repair enzymes.[33][34]

It is believed that the impact of alcohol on aging can be partly explained by alcohol's activation of the HPA axis, which stimulates glucocorticoid secretion, long-term exposure to which produces symptoms of aging.[35]

Mutation accumulation

Main article: Mutation accumulation theory

Natural selection can support lethal and harmful alleles, if their effects are felt after reproduction. The geneticist J. B. S. Haldane wondered why the dominant mutation that causes Huntington's disease remained in the population, and why natural selection had not eliminated it. The onset of this neurological disease is (on average) at age 45 and is invariably fatal within 10–20 years. Haldane assumed that, in human prehistory, few survived until age 45. Since few were alive at older ages and their contribution to the next generation was therefore small relative to the large cohorts of younger age groups, the force of selection against such late-acting deleterious mutations was correspondingly small. Therefore, a genetic load of late-acting deleterious mutations could be substantial at mutation–selection balance. This concept came to be known as the selection shadow.[36]

Peter Medawar formalised this observation in his mutation accumulation theory of aging.[37][38] "The force of natural selection weakens with increasing age—even in a theoretically immortal population, provided only that it is exposed to real hazards of mortality. If a genetic disaster... happens late enough in individual life, its consequences may be completely unimportant". Age-independent hazards such as predation, disease, and accidents, called 'extrinsic mortality', mean that even a population with negligible senescence will have fewer individuals alive in older age groups.

Biomarkers of aging

Main article: Biomarkers of aging

If different individuals age at different rates, then fecundity, mortality, and functional capacity might be better predicted by biomarkers than by chronological age.[39][40] However, graying of hair,[41] skin wrinkles and other common changes seen with aging are not better indicators of future functionality than chronological age. Biogerontologists have continued efforts to find and validate biomarkers of aging, but success thus far has been limited. Levels of CD4 and CD8 memory T cells and naive T cells have been used to give good predictions of the expected lifespan of middle-aged mice.[42]

There is interest in an epigenetic clock as a biomarker of aging, based on its ability to predict human chronological age.[43] Basic blood biochemistry and cell counts can also be used to accurately predict the chronological age.[44] It is also possible to predict the human chronological age using the transcriptomic aging clocks.[45]

Genetic determinants of aging

Main article: Genetics of aging

A number of genetic components of aging have been identified using model organisms, ranging from the simple budding yeast Saccharomyces cerevisiae to worms such as Caenorhabditis elegans and fruit flies (Drosophila melanogaster). 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 as suggested by a study of such genes in yeast.[46] Individual cells, which are genetically identical, nonetheless can have substantially different responses to outside stimuli, and markedly different lifespans, indicating the epigenetic factors play an important role in gene expression and aging as well as genetic factors.

The ability to repair DNA double-strand breaks declines with aging in mice[47] and humans.[48]

A set of rare hereditary (genetics) disorders, each called progeria, has been known for some time. 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.[49] This report suggests that DNA damage, not oxidative stress, is the cause of this form of accelerated aging.

See also

References

  1. ^ a b Kirkwood, T. B. L. (1977). "Evolution of ageing". Nature. 270 (5635): 301–304. Bibcode:1977Natur.270..301K. doi:10.1038/270301a0. ISSN 0028-0836. PMID 593350. S2CID 492012.
  2. ^ a b Nelson P, Masel J (December 2017). "Intercellular competition and the inevitability of multicellular aging". Proceedings of the National Academy of Sciences of the United States of America. 114 (49): 12982–12987. doi:10.1073/pnas.1618854114. PMC 5724245. PMID 29087299.
  3. ^ "Aging and Gerontology Glossary". Retrieved 26 February 2011.
  4. ^ López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (June 2013). "The hallmarks of aging". Cell. 153 (6): 1194–217. doi:10.1016/j.cell.2013.05.039. PMC 3836174. PMID 23746838.
  5. ^ a b Holmes GE, Bernstein C, Bernstein H (September 1992). "Oxidative and other DNA damages as the basis of aging: a review". Mutat. Res. 275 (3–6): 305–15. doi:10.1016/0921-8734(92)90034-m. PMID 1383772.
  6. ^ a b Williams GC (1957). "Pleiotropy, natural selection, and the evolution of senescence". Evolution. 11 (4): 398–411. doi:10.2307/2406060. JSTOR 2406060.
  7. ^ Austad SN (February 2009). "Comparative biology of aging". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 64 (2): 199–201. doi:10.1093/gerona/gln060. PMC 2655036. PMID 19223603.
  8. ^ Wang L, Cui J, Jin B, Zhao J, Xu H, Lu Z, et al. (January 2020). "Multifeature analyses of vascular cambial cells reveal longevity mechanisms in old Ginkgo biloba trees". Proceedings of the National Academy of Sciences of the United States of America. 117 (4): 2201–2210. doi:10.1073/pnas.1916548117. PMC 6995005. PMID 31932448.
  9. ^ Ackermann M, Stearns SC, Jenal U (June 2003). "Senescence in a bacterium with asymmetric division". Science. 300 (5627): 1920. doi:10.1126/science.1083532. PMID 12817142. S2CID 34770745.
  10. ^ Stewart EJ, Madden R, Paul G, Taddei F (February 2005). "Aging and death in an organism that reproduces by morphologically symmetric division". PLOS Biology. 3 (2): e45. doi:10.1371/journal.pbio.0030045. PMC 546039. PMID 15685293.
  11. ^ Dańko MJ, Kozłowski J, Schaible R (October 2015). "Unraveling the non-senescence phenomenon in Hydra". Journal of Theoretical Biology. 382: 137–49. Bibcode:2015JThBi.382..137D. doi:10.1016/j.jtbi.2015.06.043. PMID 26163368.
  12. ^ Tan TC, Rahman R, Jaber-Hijazi F, Felix DA, Chen C, Louis EJ, Aboobaker A (March 2012). "Telomere maintenance and telomerase activity are differentially regulated in asexual and sexual worms". Proceedings of the National Academy of Sciences of the United States of America. 109 (11): 4209–14. Bibcode:2012PNAS..109.4209T. doi:10.1073/pnas.1118885109. PMC 3306686. PMID 22371573.
  13. ^ Lisenkova AA, Grigorenko AP, Tyazhelova TV, Andreeva TV, Gusev FE, Manakhov AD, et al. (February 2017). "Complete mitochondrial genome and evolutionary analysis of Turritopsis dohrnii, the "immortal" jellyfish with a reversible life-cycle". Molecular Phylogenetics and Evolution. 107: 232–238. doi:10.1016/j.ympev.2016.11.007. PMID 27845203.
  14. ^ Piraino S, Boero F, Aeschbach B, Schmid V (June 1996). "Reversing the Life Cycle: Medusae Transforming into Polyps and Cell Transdifferentiation in Turritopsis nutricula (Cnidaria, Hydrozoa)". The Biological Bulletin. 190 (3): 302–312. doi:10.2307/1543022. JSTOR 1543022. PMID 29227703.
  15. ^ Vaupel JW, Baudisch A, Dölling M, Roach DA, Gampe J (June 2004). "The case for negative senescence". Theoretical Population Biology. 65 (4): 339–51. doi:10.1016/j.tpb.2003.12.003. PMID 15136009.
  16. ^ Viña J, Borrás C, Miquel J (2007). "Theories of ageing". IUBMB Life. 59 (4–5): 249–54. doi:10.1080/15216540601178067. PMID 17505961.
  17. ^ Kirkwood, Thomas B. L.; Austad, Steven N. (2000). "Why do we age?". Nature. 408 (6809): 233–238. Bibcode:2000Natur.408..233K. doi:10.1038/35041682. ISSN 0028-0836. PMID 11089980. S2CID 2579770.
  18. ^ Medawar, Peter Brian, Sir (1952). An unsolved problem of biology. Published for the College by H.K. Lewis. OCLC 869293719.{{cite book}}: CS1 maint: multiple names: authors list (link)
  19. ^ 1955-, Rose, Michael R. (Michael Robertson) (1991). Evolutionary biology of aging. Oxford University Press. ISBN 1-4237-6520-6. OCLC 228167629.{{cite book}}: CS1 maint: numeric names: authors list (link)
  20. ^ Tom., Kirkwood (2006). Time of Our Lives : the Science of Human Aging. Oxford University Press. ISBN 978-0-19-802939-7. OCLC 437175125.
  21. ^ Hammers M, Richardson DS, Burke T, Komdeur J (September 2013). "The impact of reproductive investment and early-life environmental conditions on senescence: support for the disposable soma hypothesis". Journal of Evolutionary Biology. 26 (9): 1999–2007. doi:10.1111/jeb.12204. hdl:11370/9cc6749c-f67d-40ab-a253-a06650c32102. PMID 23961923. S2CID 46466320.
  22. ^ Kirkwood TB, Rose MR (April 1991). "Evolution of senescence: late survival sacrificed for reproduction". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 332 (1262): 15–24. Bibcode:1991RSPTB.332...15K. doi:10.1098/rstb.1991.0028. PMID 1677205.
  23. ^ Atwood CS, Bowen RL (2011). "The reproductive-cell cycle theory of aging: an update". Experimental Gerontology. 46 (2–3): 100–7. doi:10.1016/j.exger.2010.09.007. PMID 20851172. S2CID 20998909.
  24. ^ Kirkwood, Thomas B.L. (2005). "Understanding the Odd Science of Aging". Cell. 120 (4): 437–447. doi:10.1016/j.cell.2005.01.027. ISSN 0092-8674. PMID 15734677. S2CID 7514614.
  25. ^ Harman D (July 1956). "Aging: a theory based on free radical and radiation chemistry". Journal of Gerontology. 11 (3): 298–300. doi:10.1093/geronj/11.3.298. PMID 13332224.
  26. ^ Stadtman ER (August 1992). "Protein oxidation and aging". Science. 257 (5074): 1220–4. Bibcode:1992Sci...257.1220S. doi:10.1126/science.1355616. PMID 1355616.
  27. ^ Sohal RS, Agarwal S, Dubey A, Orr WC (August 1993). "Protein oxidative damage is associated with life expectancy of houseflies". Proceedings of the National Academy of Sciences of the United States of America. 90 (15): 7255–9. Bibcode:1993PNAS...90.7255S. doi:10.1073/pnas.90.15.7255. PMC 47115. PMID 8346242.
  28. ^ Pearl R (1928). The Rate of Living, Being an Account of Some Experimental Studies on the Biology of Life Duration. New York: Alfred A. Knopf.[page needed]
  29. ^ Brunet-Rossinni AK, Austad SN (2004). "Ageing studies on bats: a review". Biogerontology. 5 (4): 211–22. doi:10.1023/B:BGEN.0000038022.65024.d8. PMID 15314271. S2CID 22755811.
  30. ^ de Magalhães JP, Costa J, Church GM (February 2007). "An analysis of the relationship between metabolism, developmental schedules, and longevity using phylogenetic independent contrasts". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 62 (2): 149–60. CiteSeerX 10.1.1.596.2815. doi:10.1093/gerona/62.2.149. PMC 2288695. PMID 17339640.
  31. ^ Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R (May 2012). "Association of coffee drinking with total and cause-specific mortality". The New England Journal of Medicine. 366 (20): 1891–904. doi:10.1056/NEJMoa1112010. PMC 3439152. PMID 22591295.
  32. ^ Yang Y, Chan SW, Hu M, Walden R, Tomlinson B (2011). "Effects of some common food constituents on cardiovascular disease". ISRN Cardiology. 2011: 397136. doi:10.5402/2011/397136. PMC 3262529. PMID 22347642.
  33. ^ Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K (2008). "Cancer and aging as consequences of un-repaired DNA damage.". In Kimura H, Suzuki A (eds.). New Research on DNA Damage. Nova Science Publishers. pp. 1–47. ISBN 978-1604565812.
  34. ^ Pan MR, Li K, Lin SY, Hung WC (May 2016). "Connecting the Dots: From DNA Damage and Repair to Aging". International Journal of Molecular Sciences. 17 (5): 685. doi:10.3390/ijms17050685. PMC 4881511. PMID 27164092.
  35. ^ Spencer RL, Hutchison KE (1999). "Alcohol, aging, and the stress response" (PDF). Alcohol Research & Health. 23 (4): 272–83. PMC 6760387. PMID 10890824.
  36. ^ Fabian D, Flatt T (2011). "The Evolution of Aging". Scitable. Nature Publishing Group.
  37. ^ Medawar PB (1946). "Old age and natural death". Modern Quarterly. 1: 30–56.
  38. ^ Medawar PB (1952). An Unsolved Problem of Biology. London: H. K. Lewis.[page needed]
  39. ^ Gasmi A, Chirumbolo S, Peana M, Mujawdiya PK, Dadar M, Menzel A, Bjørklund G (17 September 2020). "Biomarkers of Senescence during Aging as Possible Warnings to Use Preventive Measures". Current Medicinal Chemistry. 28 (8): 1471–1488. doi:10.2174/0929867327999200917150652. PMID 32942969. S2CID 221789280.
  40. ^ Baker GT, Sprott RL (1988). "Biomarkers of aging". Experimental Gerontology. 23 (4–5): 223–39. doi:10.1016/0531-5565(88)90025-3. PMID 3058488. S2CID 31039588.
  41. ^ Van Neste D, Tobin DJ (2004). "Hair cycle and hair pigmentation: dynamic interactions and changes associated with aging". Micron. 35 (3): 193–200. doi:10.1016/j.micron.2003.11.006. PMID 15036274.
  42. ^ Miller RA (April 2001). "Biomarkers of aging: prediction of longevity by using age-sensitive T-cell subset determinations in a middle-aged, genetically heterogeneous mouse population". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 56 (4): B180-6. doi:10.1093/gerona/56.4.b180. PMC 7537444. PMID 11283189.
  43. ^ Horvath S (2013). "DNA methylation age of human tissues and cell types". Genome Biology. 14 (10): R115. doi:10.1186/gb-2013-14-10-r115. PMC 4015143. PMID 24138928.
  44. ^ Putin E, Mamoshina P, Aliper A, Korzinkin M, Moskalev A, Kolosov A, et al. (May 2016). "Deep biomarkers of human aging: Application of deep neural networks to biomarker development". Aging. 8 (5): 1021–33. doi:10.18632/aging.100968. PMC 4931851. PMID 27191382.
  45. ^ Peters MJ, Joehanes R, Pilling LC, Schurmann C, Conneely KN, Powell J, et al. (October 2015). "The transcriptional landscape of age in human peripheral blood". Nature Communications. 6: 8570. Bibcode:2015NatCo...6.8570.. doi:10.1038/ncomms9570. PMC 4639797. PMID 26490707.
  46. ^ Ryley J, Pereira-Smith OM (2006). "Microfluidics device for single cell gene expression analysis in Saccharomyces cerevisiae". Yeast. 23 (14–15): 1065–73. doi:10.1002/yea.1412. PMID 17083143. S2CID 31356425.
  47. ^ Vaidya A, Mao Z, Tian X, Spencer B, Seluanov A, Gorbunova V (July 2014). "Knock-in reporter mice demonstrate that DNA repair by non-homologous end joining declines with age". PLOS Genet. 10 (7): e1004511. doi:10.1371/journal.pgen.1004511. PMC 4102425. PMID 25033455.
  48. ^ Li Z, Zhang W, Chen Y, Guo W, Zhang J, Tang H, Xu Z, Zhang H, Tao Y, Wang F, Jiang Y, Sun FL, Mao Z (November 2016). "Impaired DNA double-strand break repair contributes to the age-associated rise of genomic instability in humans". Cell Death Differ. 23 (11): 1765–77. doi:10.1038/cdd.2016.65. PMC 5071568. PMID 27391797.
  49. ^ Mounkes LC, Kozlov S, Hernandez L, Sullivan T, Stewart CL (May 2003). "A progeroid syndrome in mice is caused by defects in A-type lamins". Nature. 423 (6937): 298–301. Bibcode:2003Natur.423..298M. doi:10.1038/nature01631. PMID 12748643. S2CID 4360055.

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February 28, 2023
senescence, this, article, about, aging, whole, organisms, including, animals, aging, specifically, humans, aging, plants, plant, senescence, cells, that, stop, dividing, cellular, senescence, bacteria, bacterial, senescence, biological, aging, gradual, deteri. This article is about the aging of whole organisms including animals For aging specifically in humans see Aging For plants see Plant senescence For cells that stop dividing see Cellular senescence For bacteria see Bacterial senescence Senescence s ɪ ˈ n ɛ s e n s or biological aging is the gradual deterioration of functional characteristics in living organisms The word senescence can refer to either cellular senescence or to senescence of the whole organism Organismal senescence involves an increase in death rates and or a decrease in fecundity with increasing age at least in the latter part of an organism s life cycle Supercentenarian Ann Pouder 8 April 1807 10 July 1917 photographed on her 110th birthday A heavily lined face is common in human senescence Senescence is the inevitable fate of almost all multicellular organisms with germ soma separation 1 2 but it can be delayed The discovery in 1934 that calorie restriction can extend lifespan by 50 in rats and the existence of species having negligible senescence and potentially immortal organisms such as Hydra have motivated research into delaying senescence and thus age related diseases Rare human mutations can cause accelerated aging diseases Environmental factors may affect aging for example overexposure to ultraviolet radiation accelerates skin aging Different parts of the body may age at different rates Two organisms of the same species can also age at different rates making biological aging and chronological aging distinct concepts Contents 1 Definition and characteristics 2 Variation among species 3 Theories of aging 3 1 Evolutionary aging theories 3 1 1 Antagonistic pleiotropy 3 1 2 Cancer versus cellular senescence tradeoff theory of aging 3 1 3 Disposable soma 3 2 Programmed aging theories 3 3 Damage accumulation theories 3 3 1 The free radical theory of aging 3 3 2 Chemical damage 3 3 3 Mutation accumulation 4 Biomarkers of aging 5 Genetic determinants of aging 6 See also 7 References 8 External linksDefinition and characteristics EditOrganismal senescence is the aging of whole organisms Actuarial senescence can be defined as an increase in mortality and or a decrease in fecundity with age The Gompertz Makeham law of mortality says that the age dependent component of the mortality rate increases exponentially with age Aging is characterized by the declining ability to respond to stress increased homeostatic imbalance and increased risk of aging associated diseases including cancer and heart disease Aging has been defined as a progressive deterioration of physiological function an intrinsic age related process of loss of viability and increase in vulnerability 3 In 2013 a group of scientists defined nine hallmarks of aging that are common between organisms with emphasis on mammals genomic instability telomere attrition epigenetic alterations loss of proteostasis deregulated nutrient sensing mitochondrial dysfunction cellular senescence stem cell exhaustion altered intercellular communication 4 The environment induces damage at various levels e g damage to DNA and damage to tissues and cells by oxygen radicals widely known as free radicals and some of this damage is not repaired and thus accumulates with time 5 Cloning from somatic cells rather than germ cells may begin life with a higher initial load of damage Dolly the sheep died young from a contagious lung disease but data on an entire population of cloned individuals would be necessary to measure mortality rates and quantify aging citation needed The evolutionary theorist George Williams wrote It is remarkable that after a seemingly miraculous feat of morphogenesis a complex metazoan should be unable to perform the much simpler task of merely maintaining what is already formed 6 Variation among species EditDifferent speeds with which mortality increases with age correspond to different maximum life span among species For example a mouse is elderly at 3 years a human is elderly at 80 years 7 and ginkgo trees show little effect of age even at 667 years 8 Almost all organisms senesce including bacteria which have asymmetries between mother and daughter cells upon cell division with the mother cell experiencing aging while the daughter is rejuvenated 9 10 There is negligible senescence in some groups such as the genus Hydra 11 Planarian flatworms have apparently limitless telomere regenerative capacity fueled by a population of highly proliferative adult stem cells 12 These planarians are not biologically immortal but rather their death rate slowly increases with age Organisms that are thought to be biologically immortal would in one instance be the Turritopsis dohrnii also known as the immortal jellyfish due to its ability to revert to its youth when it undergoes stress during adulthood 13 The reproductive system is observed to remain intact and even the gonads of the Turritopsis dohrnii are existing 14 Some species exhibit negative senescence in which reproduction capability increases or is stable and mortality falls with age resulting from the advantages of increased body size during aging 15 Theories of aging EditMore than 300 different theories have been posited to explain the nature and causes of aging 16 A good theory would both explain past observations and predict the results of future experiments Theories of aging fall into two broad categories evolutionary theories of aging and mechanistic theories of aging Evolutionary theories of aging primarily explain why aging happens 17 but do not concern themselves with the molecular mechanism s that drive the process All evolutionary theories of aging rest on the basic mechanisms that the force of natural selection declines with age 18 19 Mechanistic theories of aging can be divided into theories that propose aging is programmed and damage accumulation theories i e those that propose aging to be caused by specific molecular changes occurring over time Evolutionary aging theories Edit Main article Evolution of ageing Antagonistic pleiotropy Edit Main article Antagonistic pleiotropy hypothesis One theory was proposed by George C Williams 6 and involves antagonistic pleiotropy A single gene may affect multiple traits Some traits that increase fitness early in life may also have negative effects later in life But because many more individuals are alive at young ages than at old ages even small positive effects early can be strongly selected for and large negative effects later may be very weakly selected against Williams suggested the following example Perhaps a gene codes for calcium deposition in bones which promotes juvenile survival and will therefore be favored by natural selection however this same gene promotes calcium deposition in the arteries causing negative atherosclerotic effects in old age Thus harmful biological changes in old age may result from selection for pleiotropic genes that are beneficial early in life but harmful later on In this case selection pressure is relatively high when Fisher s reproductive value is high and relatively low when Fisher s reproductive value is low Cancer versus cellular senescence tradeoff theory of aging Edit Main article Immunosenescence 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 2 Disposable soma Edit Main article Disposable soma theory of aging The disposable soma theory of aging was proposed by Thomas Kirkwood in 1977 1 20 The theory suggests that aging occurs due to a strategy in which an individual only invests in maintenance of the soma for as long as it has a realistic chance of survival 21 A species that uses resources more efficiently will live longer and therefore be able to pass on genetic information to the next generation The demands of reproduction are high so less effort is invested in repair and maintenance of somatic cells compared to germline cells in order to focus on reproduction and species survival 22 Programmed aging theories Edit Main article Programmed ageing Programmed theories of aging posit that aging is adaptive normally invoking selection for evolvability or group selection The reproductive cell cycle theory suggests that aging is regulated by changes in hormonal signaling over the lifespan 23 Only a very small minority of scientists believe aging to be programmed and the vast majority believe aging is due to some kind of damage accumulation 24 Damage accumulation theories Edit The free radical theory of aging Edit Main article Free radical theory of aging One of the most prominent theories of aging was first proposed by Harman in 1956 25 It posits that free radicals produced by dissolved oxygen radiation cellular respiration and other sources cause damage to the molecular machines in the cell and gradually wear them down This is also known as oxidative stress There is substantial evidence to back up this theory Old animals have larger amounts of oxidized proteins DNA and lipids than their younger counterparts 26 27 Chemical damage Edit Elderly Klamath woman photographed by Edward S Curtis in 1924See also DNA damage theory of aging One of the earliest aging theories was the Rate of Living Hypothesis described by Raymond Pearl in 1928 28 based on earlier work by Max Rubner which states that fast basal metabolic rate corresponds to short maximum life span While there may be some validity to the idea that for various types of specific damage detailed below that are by products of metabolism all other things being equal a fast metabolism may reduce lifespan in general this theory does not adequately explain the differences in lifespan either within or between species Calorically restricted animals process as much or more calories per gram of body mass as their ad libitum fed counterparts yet exhibit substantially longer lifespans citation needed Similarly metabolic rate is a poor predictor of lifespan for birds bats and other species that it is presumed have reduced mortality from predation and therefore have evolved long lifespans even in the presence of very high metabolic rates 29 In a 2007 analysis it was shown that when modern statistical methods for correcting for the effects of body size and phylogeny are employed metabolic rate does not correlate with longevity in mammals or birds 30 With respect to specific types of chemical damage caused by metabolism it is suggested that damage to long lived biopolymers such as structural proteins or DNA caused by ubiquitous chemical agents in the body such as oxygen and sugars are in part responsible for aging The damage can include breakage of biopolymer chains cross linking of biopolymers or chemical attachment of unnatural substituents haptens to biopolymers citation needed Under normal aerobic conditions approximately 4 of the oxygen metabolized by mitochondria is converted to superoxide ion which can subsequently be converted to hydrogen peroxide hydroxyl radical and eventually other reactive species including other peroxides and singlet oxygen which can in turn generate free radicals capable of damaging structural proteins and DNA 5 Certain metal ions found in the body such as copper and iron may participate in the process In Wilson s disease a hereditary defect that causes the body to retain copper some of the symptoms resemble accelerated senescence These processes termed oxidative stress are linked to the potential benefits of dietary polyphenol antioxidants for example in coffee 31 red wine and tea 32 Sugars such as glucose and fructose can react with certain amino acids such as lysine and arginine and certain DNA bases such as guanine to produce sugar adducts in a process called glycation These adducts can further rearrange to form reactive species which can then cross link the structural proteins or DNA to similar biopolymers or other biomolecules such as non structural proteins People with diabetes who have elevated blood sugar develop senescence associated disorders much earlier than the general population but can delay such disorders by rigorous control of their blood sugar levels There is evidence that sugar damage is linked to oxidant damage in a process termed glycoxidation Free radicals can damage proteins lipids or DNA Glycation mainly damages proteins Damaged proteins and lipids accumulate in lysosomes as lipofuscin Chemical damage to structural proteins can lead to loss of function for example damage to collagen of blood vessel walls can lead to vessel wall stiffness and thus hypertension and vessel wall thickening and reactive tissue formation atherosclerosis similar processes in the kidney can lead to kidney failure Damage to enzymes reduces cellular functionality Lipid peroxidation of the inner mitochondrial membrane reduces the electric potential and the ability to generate energy It is probably no accident that nearly all of the so called accelerated aging diseases are due to defective DNA repair enzymes 33 34 It is believed that the impact of alcohol on aging can be partly explained by alcohol s activation of the HPA axis which stimulates glucocorticoid secretion long term exposure to which produces symptoms of aging 35 Mutation accumulation Edit Main article Mutation accumulation theory Natural selection can support lethal and harmful alleles if their effects are felt after reproduction The geneticist J B S Haldane wondered why the dominant mutation that causes Huntington s disease remained in the population and why natural selection had not eliminated it The onset of this neurological disease is on average at age 45 and is invariably fatal within 10 20 years Haldane assumed that in human prehistory few survived until age 45 Since few were alive at older ages and their contribution to the next generation was therefore small relative to the large cohorts of younger age groups the force of selection against such late acting deleterious mutations was correspondingly small Therefore a genetic load of late acting deleterious mutations could be substantial at mutation selection balance This concept came to be known as the selection shadow 36 Peter Medawar formalised this observation in his mutation accumulation theory of aging 37 38 The force of natural selection weakens with increasing age even in a theoretically immortal population provided only that it is exposed to real hazards of mortality If a genetic disaster happens late enough in individual life its consequences may be completely unimportant Age independent hazards such as predation disease and accidents called extrinsic mortality mean that even a population with negligible senescence will have fewer individuals alive in older age groups Biomarkers of aging EditMain article Biomarkers of aging If different individuals age at different rates then fecundity mortality and functional capacity might be better predicted by biomarkers than by chronological age 39 40 However graying of hair 41 skin wrinkles and other common changes seen with aging are not better indicators of future functionality than chronological age Biogerontologists have continued efforts to find and validate biomarkers of aging but success thus far has been limited Levels of CD4 and CD8 memory T cells and naive T cells have been used to give good predictions of the expected lifespan of middle aged mice 42 There is interest in an epigenetic clock as a biomarker of aging based on its ability to predict human chronological age 43 Basic blood biochemistry and cell counts can also be used to accurately predict the chronological age 44 It is also possible to predict the human chronological age using the transcriptomic aging clocks 45 Genetic determinants of aging EditMain article Genetics of aging A number of genetic components of aging have been identified using model organisms ranging from the simple budding yeast Saccharomyces cerevisiae to worms such as Caenorhabditis elegans and fruit flies Drosophila melanogaster 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 as suggested by a study of such genes in yeast 46 Individual cells which are genetically identical nonetheless can have substantially different responses to outside stimuli and markedly different lifespans indicating the epigenetic factors play an important role in gene expression and aging as well as genetic factors The ability to repair DNA double strand breaks declines with aging in mice 47 and humans 48 A set of rare hereditary genetics disorders each called progeria has been known for some time 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 49 This report suggests that DNA damage not oxidative stress is the cause of this form of accelerated aging See also EditAgeing Aging brain Aging associated diseases Anti aging movement DNA repair Free radicals Genetics of aging Geriatrics Gerontology Homeostatic capacity Immortality Life extension Index of topics related to life extension Mitohormesis Old age Oxidative stress Phenoptosis Plant senescence Programmed cell death Regenerative medicine Rejuvenation SAGE KE Stem cell theory of aging Strategies for engineered negligible senescence SENS Sub lethal damage Transgenerational designReferences Edit a b Kirkwood T B L 1977 Evolution of ageing Nature 270 5635 301 304 Bibcode 1977Natur 270 301K doi 10 1038 270301a0 ISSN 0028 0836 PMID 593350 S2CID 492012 a b Nelson P Masel J December 2017 Intercellular competition and the inevitability of multicellular aging Proceedings of the National Academy of Sciences of the United States of America 114 49 12982 12987 doi 10 1073 pnas 1618854114 PMC 5724245 PMID 29087299 Aging and Gerontology Glossary Retrieved 26 February 2011 Lopez Otin C Blasco MA Partridge L Serrano M Kroemer G June 2013 The hallmarks of aging Cell 153 6 1194 217 doi 10 1016 j cell 2013 05 039 PMC 3836174 PMID 23746838 a b Holmes GE Bernstein C Bernstein H September 1992 Oxidative and other DNA damages as the basis of aging a review Mutat Res 275 3 6 305 15 doi 10 1016 0921 8734 92 90034 m PMID 1383772 a b Williams GC 1957 Pleiotropy natural selection and the evolution of senescence Evolution 11 4 398 411 doi 10 2307 2406060 JSTOR 2406060 Austad SN February 2009 Comparative biology of aging The Journals of Gerontology Series A Biological Sciences and Medical Sciences 64 2 199 201 doi 10 1093 gerona gln060 PMC 2655036 PMID 19223603 Wang L Cui J Jin B Zhao J Xu H Lu Z et al January 2020 Multifeature analyses of vascular cambial cells reveal longevity mechanisms in old Ginkgo biloba trees Proceedings of the National Academy of Sciences of the United States of America 117 4 2201 2210 doi 10 1073 pnas 1916548117 PMC 6995005 PMID 31932448 Ackermann M Stearns SC Jenal U June 2003 Senescence in a bacterium with asymmetric division Science 300 5627 1920 doi 10 1126 science 1083532 PMID 12817142 S2CID 34770745 Stewart EJ Madden R Paul G Taddei F February 2005 Aging and death in an organism that reproduces by morphologically symmetric division PLOS Biology 3 2 e45 doi 10 1371 journal pbio 0030045 PMC 546039 PMID 15685293 Danko MJ Kozlowski J Schaible R October 2015 Unraveling the non senescence phenomenon in Hydra Journal of Theoretical Biology 382 137 49 Bibcode 2015JThBi 382 137D doi 10 1016 j jtbi 2015 06 043 PMID 26163368 Tan TC Rahman R Jaber Hijazi F Felix DA Chen C Louis EJ Aboobaker A March 2012 Telomere maintenance and telomerase activity are differentially regulated in asexual and sexual worms Proceedings of the National Academy of Sciences of the United States of America 109 11 4209 14 Bibcode 2012PNAS 109 4209T doi 10 1073 pnas 1118885109 PMC 3306686 PMID 22371573 Lisenkova AA Grigorenko AP Tyazhelova TV Andreeva TV Gusev FE Manakhov AD et al February 2017 Complete mitochondrial genome and evolutionary analysis of Turritopsis dohrnii the immortal jellyfish with a reversible life cycle Molecular Phylogenetics and Evolution 107 232 238 doi 10 1016 j ympev 2016 11 007 PMID 27845203 Piraino S Boero F Aeschbach B Schmid V June 1996 Reversing the Life Cycle Medusae Transforming into Polyps and Cell Transdifferentiation in Turritopsis nutricula Cnidaria Hydrozoa The Biological Bulletin 190 3 302 312 doi 10 2307 1543022 JSTOR 1543022 PMID 29227703 Vaupel JW Baudisch A Dolling M Roach DA Gampe J June 2004 The case for negative senescence Theoretical Population Biology 65 4 339 51 doi 10 1016 j tpb 2003 12 003 PMID 15136009 Vina J Borras C Miquel J 2007 Theories of ageing IUBMB Life 59 4 5 249 54 doi 10 1080 15216540601178067 PMID 17505961 Kirkwood Thomas B L Austad Steven N 2000 Why do we age Nature 408 6809 233 238 Bibcode 2000Natur 408 233K doi 10 1038 35041682 ISSN 0028 0836 PMID 11089980 S2CID 2579770 Medawar Peter Brian Sir 1952 An unsolved problem of biology Published for the College by H K Lewis OCLC 869293719 a href Template Cite book html title Template Cite book cite book a CS1 maint multiple names authors list link 1955 Rose Michael R Michael Robertson 1991 Evolutionary biology of aging Oxford University Press ISBN 1 4237 6520 6 OCLC 228167629 a href Template Cite book html title Template Cite book cite book a CS1 maint numeric names authors list link Tom Kirkwood 2006 Time of Our Lives the Science of Human Aging Oxford University Press ISBN 978 0 19 802939 7 OCLC 437175125 Hammers M Richardson DS Burke T Komdeur J September 2013 The impact of reproductive investment and early life environmental conditions on senescence support for the disposable soma hypothesis Journal of Evolutionary Biology 26 9 1999 2007 doi 10 1111 jeb 12204 hdl 11370 9cc6749c f67d 40ab a253 a06650c32102 PMID 23961923 S2CID 46466320 Kirkwood TB Rose MR April 1991 Evolution of senescence late survival sacrificed for reproduction Philosophical Transactions of the Royal Society of London Series B Biological Sciences 332 1262 15 24 Bibcode 1991RSPTB 332 15K doi 10 1098 rstb 1991 0028 PMID 1677205 Atwood CS Bowen RL 2011 The reproductive cell cycle theory of aging an update Experimental Gerontology 46 2 3 100 7 doi 10 1016 j exger 2010 09 007 PMID 20851172 S2CID 20998909 Kirkwood Thomas B L 2005 Understanding the Odd Science of Aging Cell 120 4 437 447 doi 10 1016 j cell 2005 01 027 ISSN 0092 8674 PMID 15734677 S2CID 7514614 Harman D July 1956 Aging a theory based on free radical and radiation chemistry Journal of Gerontology 11 3 298 300 doi 10 1093 geronj 11 3 298 PMID 13332224 Stadtman ER August 1992 Protein oxidation and aging Science 257 5074 1220 4 Bibcode 1992Sci 257 1220S doi 10 1126 science 1355616 PMID 1355616 Sohal RS Agarwal S Dubey A Orr WC August 1993 Protein oxidative damage is associated with life expectancy of houseflies Proceedings of the National Academy of Sciences of the United States of America 90 15 7255 9 Bibcode 1993PNAS 90 7255S doi 10 1073 pnas 90 15 7255 PMC 47115 PMID 8346242 Pearl R 1928 The Rate of Living Being an Account of Some Experimental Studies on the Biology of Life Duration New York Alfred A Knopf page needed Brunet Rossinni AK Austad SN 2004 Ageing studies on bats a review Biogerontology 5 4 211 22 doi 10 1023 B BGEN 0000038022 65024 d8 PMID 15314271 S2CID 22755811 de Magalhaes JP Costa J Church GM February 2007 An analysis of the relationship between metabolism developmental schedules and longevity using phylogenetic independent contrasts The Journals of Gerontology Series A Biological Sciences and Medical Sciences 62 2 149 60 CiteSeerX 10 1 1 596 2815 doi 10 1093 gerona 62 2 149 PMC 2288695 PMID 17339640 Freedman ND Park Y Abnet CC Hollenbeck AR Sinha R May 2012 Association of coffee drinking with total and cause specific mortality The New England Journal of Medicine 366 20 1891 904 doi 10 1056 NEJMoa1112010 PMC 3439152 PMID 22591295 Yang Y Chan SW Hu M Walden R Tomlinson B 2011 Effects of some common food constituents on cardiovascular disease ISRN Cardiology 2011 397136 doi 10 5402 2011 397136 PMC 3262529 PMID 22347642 Bernstein H Payne CM Bernstein C Garewal H Dvorak K 2008 Cancer and aging as consequences of un repaired DNA damage In Kimura H Suzuki A eds New Research on DNA Damage Nova Science Publishers pp 1 47 ISBN 978 1604565812 Pan MR Li K Lin SY Hung WC May 2016 Connecting the Dots From DNA Damage and Repair to Aging International Journal of Molecular Sciences 17 5 685 doi 10 3390 ijms17050685 PMC 4881511 PMID 27164092 Spencer RL Hutchison KE 1999 Alcohol aging and the stress response PDF Alcohol Research amp Health 23 4 272 83 PMC 6760387 PMID 10890824 Fabian D Flatt T 2011 The Evolution of Aging Scitable Nature Publishing Group Medawar PB 1946 Old age and natural death Modern Quarterly 1 30 56 Medawar PB 1952 An Unsolved Problem of Biology London H K Lewis page needed Gasmi A Chirumbolo S Peana M Mujawdiya PK Dadar M Menzel A Bjorklund G 17 September 2020 Biomarkers of Senescence during Aging as Possible Warnings to Use Preventive Measures Current Medicinal Chemistry 28 8 1471 1488 doi 10 2174 0929867327999200917150652 PMID 32942969 S2CID 221789280 Baker GT Sprott RL 1988 Biomarkers of aging Experimental Gerontology 23 4 5 223 39 doi 10 1016 0531 5565 88 90025 3 PMID 3058488 S2CID 31039588 Van Neste D Tobin DJ 2004 Hair cycle and hair pigmentation dynamic interactions and changes associated with aging Micron 35 3 193 200 doi 10 1016 j micron 2003 11 006 PMID 15036274 Miller RA April 2001 Biomarkers of aging prediction of longevity by using age sensitive T cell subset determinations in a middle aged genetically heterogeneous mouse population The Journals of Gerontology Series A Biological Sciences and Medical Sciences 56 4 B180 6 doi 10 1093 gerona 56 4 b180 PMC 7537444 PMID 11283189 Horvath S 2013 DNA methylation age of human tissues and cell types Genome Biology 14 10 R115 doi 10 1186 gb 2013 14 10 r115 PMC 4015143 PMID 24138928 Putin E Mamoshina P Aliper A Korzinkin M Moskalev A Kolosov A et al May 2016 Deep biomarkers of human aging Application of deep neural networks to biomarker development Aging 8 5 1021 33 doi 10 18632 aging 100968 PMC 4931851 PMID 27191382 Peters MJ Joehanes R Pilling LC Schurmann C Conneely KN Powell J et al October 2015 The transcriptional landscape of age in human peripheral blood Nature Communications 6 8570 Bibcode 2015NatCo 6 8570 doi 10 1038 ncomms9570 PMC 4639797 PMID 26490707 Ryley J Pereira Smith OM 2006 Microfluidics device for single cell gene expression analysis in Saccharomyces cerevisiae Yeast 23 14 15 1065 73 doi 10 1002 yea 1412 PMID 17083143 S2CID 31356425 Vaidya A Mao Z Tian X Spencer B Seluanov A Gorbunova V July 2014 Knock in reporter mice demonstrate that DNA repair by non homologous end joining declines with age PLOS Genet 10 7 e1004511 doi 10 1371 journal pgen 1004511 PMC 4102425 PMID 25033455 Li Z Zhang W Chen Y Guo W Zhang J Tang H Xu Z Zhang H Tao Y Wang F Jiang Y Sun FL Mao Z November 2016 Impaired DNA double strand break repair contributes to the age associated rise of genomic instability in humans Cell Death Differ 23 11 1765 77 doi 10 1038 cdd 2016 65 PMC 5071568 PMID 27391797 Mounkes LC Kozlov S Hernandez L Sullivan T Stewart CL May 2003 A progeroid syndrome in mice is caused by defects in A type lamins Nature 423 6937 298 301 Bibcode 2003Natur 423 298M doi 10 1038 nature01631 PMID 12748643 S2CID 4360055 External links Edit Look up senescence in Wiktionary the free dictionary Wikimedia Commons has media related to Senescence Senescence at Curlie Retrieved from https en wikipedia org w index php title Senescence amp oldid 1138929309, wikipedia, wiki, book, books, library,

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