Senescence: Difference between revisions

{{about|the aging of whole organisms including animals|aging specifically in humans|AgingAgeing|plants|Plant senescence|cells that stop dividing|Cellular senescence|bacteria|Bacterial senescence}}

{{Use dmyAmerican datesEnglish|date=OctoberMay 20192024}}

'''Senescence''' ({{IPAc-en|s|ɪ|ˈ|n|ɛ|s|ə|n|s}}) or '''biological aging''' is the inevitablegradual fatedeterioration of [[NegligibleFunction senescence(biology)|almostfunctional]] allcharacteristics in living organisms. Whole [[multicellular organism]]s withsenescence involves an increase in [[germmortality cellrate|germdeath rates]]- or a decrease in [[somatic cell|somafecundity]] separationwith increasing age, at least in the later part of an organism's [[biological life cycle|life cycle]].<ref name=":0">{{Cite journal|last=Kirkwood|first=T. B. L.|date=1977|title=Evolution of ageing|url=http://dx.doi.org/10.1038/270301a0|journal=Nature|volume=270|issue=5635|pages=301–304301–4|doi=10.1038/270301a0|pmid=593350|bibcode=1977Natur.270..301K|s2cid=492012|issnaccess-date=002831 January 2022|archive-0836date=15 November 2023|archive-url=https://web.archive.org/web/20231115062848/https://www.nature.com/articles/270301a0|url-status=live}}</ref><ref name="nelson_2017">{{cite journal | vauthors = Nelson P, Masel J | title = Intercellular competition and the inevitability of multicellular aging | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 49 | pages = 12982–1298712982–7 | date = December 2017 | pmid = 29087299 | pmc = 5724245 | doi = 10.1073/pnas.1618854114 | bibcode = 2017PNAS..11412982N | doi-access = free }}</ref> butHowever, itthe resulting effects of senescence can be delayed. The 1934 discovery that [[calorie restriction]] can [[Life extension|extend lifespans]] by 50% in rats, the existence of species having [[negligible senescence]], and the existence of potentially immortal organisms such as members of the [[genus]] ''[[Hydra (genus)|Hydra]]'' have motivated research into [[Life extension|delaying senescence]] and thus [[age-related disease]]s. Rare human mutations can cause [[accelerated aging disease]]s.

Environmental [[Gerontogens|factors]] may affect [[aging]] – for example, overexposure to [[ultraviolet radiation]] accelerates [[skin aging]]. Different parts of the body may age at different rates and distinctly, including [[Aging brain|the brain]], [[Cardiovascular disease#Age|the cardiovascular system]], and <!--Skeletal muscle#Atrophy [[Aging musculature]]-->muscle. Similarly, functions may distinctly decline with aging, including [[Aging movement control|movement control]] and [[Memory and aging|memory]]. Two organisms of the same species can also age at different rates, making biological aging and chronological aging distinct concepts.

''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]] [[exponential growth|increases exponentially]] with age.

[[Aging]] is characterized by the declining ability to respond to stress, increased [[homeostasis|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."<ref>{{Cite web |title=Aging and Gerontology Glossary |url=http://www.senescence.info/glossary.html |access-date=26 February 2011 |archive-date=19 October 2019 |archive-url=https://web.archive.org/web/20191019200702/http://www.senescence.info/glossary.html |url-status=live }}</ref>

* [[dysbiosis]]<ref name="10.1016/j.cell.2022.11.001">{{cite journal |last1=López-Otín |first1=Carlos |last2=Blasco |first2=Maria A. |last3=Partridge |first3=Linda |last4=Serrano |first4=Manuel |last5=Kroemer |first5=Guido |title=Hallmarks of aging: An expanding universe |journal=Cell |date=19 January 2023 |volume=186 |issue=2 |pages=243–278 |doi=10.1016/j.cell.2022.11.001 |pmid=36599349 |s2cid=255394876 |url=https://www.cell.com/cell/fulltext/S0092-8674(22)01377-0 |language=English |issn=0092-8674 |urldoi-access=subscription |access-date=17 February 2023 |archive-date=17 February 2023 |archive-url=https://web.archive.org/web/20230217232035/https://www.cell.com/cell/fulltext/S0092-8674(22)01377-0 |url-status=livefree }}</ref>

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,<ref>{{cite journal | vauthors = Austad SN | title = Comparative biology of aging | journal = The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences | volume = 64 | issue = 2 | pages = 199–201 | date = February 2009 | pmid = 19223603 | pmc = 2655036 | doi = 10.1093/gerona/gln060 }}</ref> and [[ginkgo]] trees show little effect of age even at 667 years.<ref name="Wang">{{cite journal | vauthors = Wang L, Cui J, Jin B, Zhao J, Xu H, Lu Z, Li W, Li X, Li L, Liang E, Rao X, Wang S, Fu C, Cao F, Dixon RA, Lin J | display-authors = 6 | title = Multifeature analyses of vascular cambial cells reveal longevity mechanisms in old ''Ginkgo biloba'' trees | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 117 | issue = 4 | pages = 2201–22102201–10 | date = January 2020 | pmid = 31932448 | pmc = 6995005 | doi = 10.1073/pnas.1916548117 | bibcode = 2020PNAS..117.2201W | doi-access = free }}</ref>

Almost all organisms senesce, including [[bacterial senescence|bacteria]] which have asymmetries between "mother" and "daughter" cells upon [[cell division]], with the mother cell experiencing aging, while the daughter is rejuvenated.<ref>{{cite journal | vauthors = Ackermann M, Stearns SC, Jenal U | title = Senescence in a bacterium with asymmetric division | journal = Science | volume = 300 | issue = 5627 | pages = 1920 | date = June 2003 | pmid = 12817142 | doi = 10.1126/science.1083532 | s2cid = 34770745 }}</ref><ref>{{cite journal | vauthors = Stewart EJ, Madden R, Paul G, Taddei F | title = Aging and death in an organism that reproduces by morphologically symmetric division | journal = PLOS Biology | volume = 3 | issue = 2 | pages = e45 | date = February 2005 | pmid = 15685293 | pmc = 546039 | doi = 10.1371/journal.pbio.0030045 | doi-access = free }}</ref> There is [[negligible senescence]] in some groups, such as the genus ''[[Hydra (genus)|Hydra]]''.<ref name="Dańko Kozłowski Schaible 2015 pp. 137–149">{{cite journal | vauthors = Dańko MJ, Kozłowski J, Schaible R | title = Unraveling the non-senescence phenomenon in Hydra | journal = Journal of Theoretical Biology | volume = 382 | pages = 137–49 | date = October 2015 | pmid = 26163368 | doi = 10.1016/j.jtbi.2015.06.043 | bibcode = 2015JThBi.382..137D | doi-access = free }}</ref> [[Planarian]] [[flatworm]]s have "apparently limitless [[telomere]] regenerative capacity fueled by a population of highly proliferative adult [[stem cell]]s."<ref>{{cite journal | vauthors = Tan TC, Rahman R, Jaber-Hijazi F, Felix DA, Chen C, Louis EJ, Aboobaker A | title = Telomere maintenance and telomerase activity are differentially regulated in asexual and sexual worms | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 11 | pages = 4209–14 | date = March 2012 | pmid = 22371573 | pmc = 3306686 | doi = 10.1073/pnas.1118885109 | name-list-style = amp | bibcode = 2012PNAS..109.4209T | doi-access = free }}</ref> These planarians are not [[Biological immortality|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|''Turritopsis'' ''dohrnii'']], also known as the "immortal jellyfish", due to its ability to revert to its youth when it undergoes stress during adulthood.<ref>{{cite journal | vauthors = Lisenkova AA, Grigorenko AP, Tyazhelova TV, Andreeva TV, Gusev FE, Manakhov AD, Goltsov AY, Piraino S, Miglietta MP, Rogaev EI | display-authors = 6 | title = Complete mitochondrial genome and evolutionary analysis of Turritopsis dohrnii, the "immortal" jellyfish with a reversible life-cycle | journal = Molecular Phylogenetics and Evolution | volume = 107 | pages = 232–238232–8 | date = February 2017 | pmid = 27845203 | doi = 10.1016/j.ympev.2016.11.007 | doi-access = free | bibcode = 2017MolPE.107..232L }}</ref> The [[reproductive system]] is observed to remain intact, and even the gonads of the ''Turritopsis'' ''dohrnii'' are existing.<ref>{{cite journal | vauthors = Piraino S, Boero F, Aeschbach B, Schmid V | title = Reversing the Life Cycle: Medusae Transforming into Polyps and Cell Transdifferentiation in Turritopsis nutricula (Cnidaria, Hydrozoa) | journal = The Biological Bulletin | volume = 190 | issue = 3 | pages = 302–312 | date = June 1996 | pmid = 29227703 | doi = 10.2307/1543022 | jstor = 1543022 }}</ref>

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.<ref>{{cite journal | vauthors = Vaupel JW, Baudisch A, Dölling M, Roach DA, Gampe J | title = The case for negative senescence | journal = Theoretical Population Biology | volume = 65 | issue = 4 | pages = 339–51 | date = June 2004 | pmid = 15136009 | doi = 10.1016/j.tpb.2003.12.003 | bibcode = 2004TPBio..65..339W }}</ref>

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,<ref>{{Cite journal|last1=Kirkwood|first1=Thomas B. L.|last2=Austad|first2=Steven N.|date=2000|title=Why do we age?|url=http://dx.doi.org/10.1038/35041682|journal=Nature|volume=408|issue=6809|pages=233–238233–8|doi=10.1038/35041682|pmid=11089980|bibcode=2000Natur.408..233K|s2cid=2579770|issnaccess-date=002831 January 2022|archive-0836date=15 November 2023|archive-url=https://web.archive.org/web/20231115062849/https://www.nature.com/articles/35041682|url-status=live}}</ref> 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.<ref>{{Cite book |author-link=Peter Medawar, |last=Medawar |first=Peter Brian, Sir|url=http://worldcat.org/oclc/869293719|title=An unsolved problem of biology|date=1952|publisher=Published for the College by [[H. K. Lewis & Co. Ltd.|H.K. Lewis]]|oclc=869293719 }}</ref><ref>{{Cite book|last=Rose|first=Michael R.|url=http://worldcat.org/oclc/228167629|title=Evolutionary biology of aging|date=1991|publisher=Oxford University Press|isbn=1-4237-6520-6|oclc=228167629|access-date=31 January 2022|archive-date=15 November 2023|archive-url=https://web.archive.org/web/20231115063010/https://search.worldcat.org/title/228167629|url-status=live}}</ref> 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.

The disposable soma theory of aging was proposed by [[Tom Kirkwood|Thomas Kirkwood]] in 1977.<ref name=":0" /><ref>{{Cite book|first=Tom|last=Kirkwood|url=http://worldcat.org/oclc/437175125|title=Time of Our Lives : the Science of Human Aging.|date=2006|publisher=Oxford University Press|isbn=978-0-19-802939-7|oclc=437175125|access-date=31 January 2022|archive-date=15 November 2023|archive-url=https://web.archive.org/web/20231115062955/https://search.worldcat.org/title/437175125|url-status=live}}</ref> 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.<ref>{{cite journal | vauthors = Hammers M, Richardson DS, Burke T, Komdeur J | title = The impact of reproductive investment and early-life environmental conditions on senescence: support for the disposable soma hypothesis | journal = Journal of Evolutionary Biology | volume = 26 | issue = 9 | pages = 1999–2007 | date = September 2013 | pmid = 23961923 | doi = 10.1111/jeb.12204 | hdl-access = free | s2cid = 46466320 | hdl = 11370/9cc6749c-f67d-40ab-a253-a06650c32102 }}</ref> 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 cell]]s, in order to focus on reproduction and species survival.<ref>{{cite journal | vauthors = Kirkwood TB, Rose MR | title = Evolution of senescence: late survival sacrificed for reproduction | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 332 | issue = 1262 | pages = 15–24 | date = April 1991 | pmid = 1677205 | doi = 10.1098/rstb.1991.0028 | bibcode = 1991RSPTB.332...15K }}</ref>

One of the most prominent theories of aging was first proposed by Harman in 1956.<ref>{{cite journal | vauthors = Harman D | title = Aging: a theory based on free radical and radiation chemistry | journal = Journal of Gerontology | volume = 11 | issue = 3 | pages = 298–300 | date = July 1956 | pmid = 13332224 | doi = 10.1093/geronj/11.3.298 | hdl = 2027/mdp.39015086547422 | hdl-access = free }}</ref> It posits that [[Radical (chemistry)|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.<ref>{{cite journal | vauthors = Stadtman ER | title = Protein oxidation and aging | journal = Science | volume = 257 | issue = 5074 | pages = 1220–4 | date = August 1992 | pmid = 1355616 | doi = 10.1126/science.1355616 | bibcode = 1992Sci...257.1220S | url = https://zenodo.org/record/1230934 | access-date = 21 July 2021 | archive-date = 31 July 2021 | archive-url = https://web.archive.org/web/20210731091110/https://zenodo.org/record/1230934 | url-status = live }}</ref><ref>{{cite journal | vauthors = Sohal RS, Agarwal S, Dubey A, Orr WC | title = Protein oxidative damage is associated with life expectancy of houseflies | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 15 | pages = 7255–9 | date = August 1993 | pmid = 8346242 | pmc = 47115 | doi = 10.1073/pnas.90.15.7255 | bibcode = 1993PNAS...90.7255S | doi-access = free }}</ref>

[[Image:Edward S. Curtis Collection People 086.jpg|thumb|200pxupright=.8|Elderly [[Klamath people|Klamath]] woman photographed by [[Edward S. Curtis]] in 1924]]{{See also|DNA damage theory of aging}}

Under normal [[wikt:aerobic|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 (chemistry)|radical]] and eventually other reactive species including other [[peroxide]]s and [[singlet oxygen]], which can, in turn, generate [[radical (chemistry)|free radical]]s capable of damaging structural proteins and DNA.<ref name="pmid1383772" /> Certain metal [[ion]]s found in the body, such as [[copper]] and [[iron]], may participate in the process. (In [[Wilson's disease]], a [[genetic disorder|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]] [[antioxidant]]s, for example in [[coffee]],<ref>{{cite journal | vauthors = Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R | title = Association of coffee drinking with total and cause-specific mortality | journal = The New England Journal of Medicine | volume = 366 | issue = 20 | pages = 1891–904 | date = May 2012 | pmid = 22591295 | pmc = 3439152 | doi = 10.1056/NEJMoa1112010 }}</ref> and [[green tea|tea]].<ref>{{cite journal | vauthors = Yang Y, Chan SW, Hu M, Walden R, Tomlinson B | title = Effects of some common food constituents on cardiovascular disease | journal = ISRN Cardiology | volume = 2011 | pages = 397136 | year = 2011 | pmid = 22347642 | pmc = 3262529 | doi = 10.5402/2011/397136 | doi-access = free }}</ref> However their typically positive effects on lifespans when consumption is moderate<ref>{{cite journal |last1=Poole |first1=Robin |last2=Kennedy |first2=Oliver J. |last3=Roderick |first3=Paul |last4=Fallowfield |first4=Jonathan A. |last5=Hayes |first5=Peter C. |last6=Parkes |first6=Julie |title=Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes |journal=BMJ |date=22 November 2017 |volume=359 |pages=j5024 |doi=10.1136/bmj.j5024 |pmid=29167102 |pmc=5696634 |language=en |issn=0959-8138}}</ref><ref>{{cite journal |last1=O'Keefe |first1=James H. |last2=DiNicolantonio |first2=James J. |last3=Lavie |first3=Carl J. |title=Coffee for Cardioprotection and Longevity |journal=Progress in Cardiovascular Diseases |date=1 May 2018 |volume=61 |issue=1 |pages=38–42 |doi=10.1016/j.pcad.2018.02.002 |pmid=29474816 |language=en |issn=0033-0620}}</ref><ref>{{cite journal |last1=Grosso |first1=Giuseppe |last2=Godos |first2=Justyna |last3=Galvano |first3=Fabio |last4=Giovannucci |first4=Edward L. |title=Coffee, Caffeine, and Health Outcomes: An Umbrella Review |journal=Annual Review of Nutrition |date=21 August 2017 |volume=37 |issue=1 |pages=131–156 |doi=10.1146/annurev-nutr-071816-064941 |pmid=28826374 |language=en |issn=0199-9885}}</ref> have also been explained by effects on [[autophagy]],<ref>{{cite journal |last1=Dirks-Naylor |first1=Amie J. |title=The benefits of coffee on skeletal muscle |journal=Life Sciences |date=15 December 2015 |volume=143 |pages=182–186182–6 |doi=10.1016/j.lfs.2015.11.005 |pmid=26546720 |language=en |issn=0024-3205}}</ref> [[glucose metabolism]]<ref>{{cite journal |last1=Reis |first1=Caio E. G. |last2=Dórea |first2=José G. |last3=da Costa |first3=Teresa H. M. |title=Effects of coffee consumption on glucose metabolism: A systematic review of clinical trials |journal=Journal of Traditional and Complementary Medicine |date=1 July 2019 |volume=9 |issue=3 |pages=184–191 |doi=10.1016/j.jtcme.2018.01.001 |pmid=31193893 |pmc=6544578 |language=en |issn=2225-4110}}</ref> and [[AMP-activated protein kinase|AMPK]].<ref>{{cite journal |last1=Loureiro |first1=Laís Monteiro Rodrigues |last2=Reis |first2=Caio Eduardo Gonçalves |last3=Costa |first3=Teresa Helena Macedo da |title=Effects of Coffee Components on Muscle Glycogen Recovery: A Systematic Review |journal=International Journal of Sport Nutrition and Exercise Metabolism |date=1 May 2018 |volume=28 |issue=3 |pages=284–293 |doi=10.1123/ijsnem.2017-0342 |pmid=29345166 |language=en |issn=1543-2742}}</ref>

[[Reactive oxygen species|Free radicals]] can damage proteins, [[lipid]]s or [[DNA damage theory of aging|DNA]]. [[Glycation]] mainly damages proteins. Damaged proteins and lipids accumulate in [[lysosome]]s 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 [[enzyme]]s reduces cellular functionality. Lipid [[redox|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 disease]]s" are due to defective [[DNA repair]] enzymes.<ref name="KimuraSuzuki2008">{{cite book| vauthors = Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K |url={{https://books.google .com/books |plainurl=y |?id=arjZMwAACAAJ|page&pg=1}}PA1|title=New Research on DNA Damage|publisher=Nova Science Publishers|year=2008|isbn=978-1604565812| veditors = Kimura H, Suzuki A |pages=1–47 |chapter= Cancer and aging as consequences of un-repaired DNA damage. |chapter-url=https://www.novapublishers.com/catalog/product_info.php?products_id=43247|access-date=4 February 2016|archive-date=15 November 2023|archive-url=https://web.archive.org/web/20231115062953/https://books.google.com/books?id=arjZMwAACAAJ&pg=PA1|url-status=live}}</ref><ref name="pmid27164092">{{cite journal | vauthors = Pan MR, Li K, Lin SY, Hung WC | title = Connecting the Dots: From DNA Damage and Repair to Aging | journal = International Journal of Molecular Sciences | volume = 17 | issue = 5 | pages = 685 | date = May 2016 | pmid = 27164092 | pmc = 4881511 | doi = 10.3390/ijms17050685 | doi-access = free }}</ref>

[[Natural selection]] can support lethal and harmful [[allele]]s, 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]].<ref>{{cite web |url=http://www.nature.com/scitable/knowledge/library/the-evolution-of-aging-23651151 |title=The Evolution of Aging | vauthors = Fabian D, Flatt T |date=2011 |websitework=[[Scitable]]Nature Education |publisherurl=[[Nature Publishing Group]]https://core.ac.uk/download/pdf/190039034.pdf}}</ref>

[[Peter Medawar]] formalised this observation in his [[Evolution of ageing#Mutation accumulation|mutation accumulation theory]] of aging.<ref>{{Cite journal| vauthors = Medawar PB |year=1946 |title=Old age and natural death |journal=Modern Quarterly |volume=1 |pages=30–56}}</ref><ref>{{Cite book harvnb| vauthors = Medawar PB | year=1952 | title=An Unsolved Problem of Biology | publisher=[[H. K. Lewis & Co. Ltd.]] | location=London}}{{Page needed|date=September 2010}}</ref> "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.

A study concluded that [[retrovirus]]es in the [[human genome]]s can become awakened from dormant states and contribute to aging which can be blocked by [[Neutralizing antibody|neutralizing antibodies]], alleviating "cellular senescence and tissue degeneration and, to some extent, organismal aging".<ref>{{cite journal |last1=Liu |first1=Xiaoqian |last2=Liu |first2=Zunpeng |last3=Wu |first3=Zeming |last4=Ren |first4=Jie |last5=Fan |first5=Yanling |last6=Sun |first6=Liang |last7=Cao |first7=Gang |last8=Niu |first8=Yuyu |last9=Zhang |first9=Baohu |last10=Ji |first10=Qianzhao |last11=Jiang |first11=Xiaoyu |last12=Wang |first12=Cui |last13=Wang |first13=Qiaoran |last14=Ji |first14=Zhejun |last15=Li |first15=Lanzhu |last16=Esteban |first16=Concepcion Rodriguez |last17=Yan |first17=Kaowen |last18=Li |first18=Wei |last19=Cai |first19=Yusheng |last20=Wang |first20=Si |last21=Zheng |first21=Aihua |last22=Zhang |first22=Yong E. |last23=Tan |first23=Shengjun |last24=Cai |first24=Yingao |last25=Song |first25=Moshi |last26=Lu |first26=Falong |last27=Tang |first27=Fuchou |last28=Ji |first28=Weizhi |last29=Zhou |first29=Qi |last30=Belmonte |first30=Juan Carlos Izpisua |last31=Zhang |first31=Weiqi |last32=Qu |first32=Jing |last33=Liu |first33=Guang-Hui |title=Resurrection of endogenous retroviruses during aging reinforces senescence |journal=Cell |date=19 January 2023 |volume=186 |issue=2 |pages=287–304.e26 |doi=10.1016/j.cell.2022.12.017 |pmid=36610399 |s2cid=232060038 |url=https://www.cell.com/cell/fulltext/S0092-8674(22)01530-6 |language=English |issn=0092doi-8674 |access-date=17 February 2023 |archive-date=27 January 2023 |archive-url=https://web.archive.org/web/20230127111022/https://www.cell.com/cell/fulltext/S0092-8674(22)01530-6 |url-status=livefree }}

* Expert explanation of the study: {{cite news |title=Aging and Retroviruses |url=https://www.science.org/content/blog-post/aging-and-retroviruses |access-date=17 February 2023 |work=Science |language=en |archive-date=17 February 2023 |archive-url=https://web.archive.org/web/20230217232037/https://www.science.org/content/blog-post/aging-and-retroviruses |url-status=live }}</ref>

If different individuals age at different rates, then fecundity, mortality, and functional capacity might be better predicted by [[biomarker]]s than by chronological age.<ref name="Gasmi">{{cite journal | vauthors = Gasmi A, Chirumbolo S, Peana M, Mujawdiya PK, Dadar M, Menzel A, Bjørklund G | title = Biomarkers of Senescence during Aging as Possible Warnings to Use Preventive Measures | journal = Current Medicinal Chemistry | volume = 28 | issue = 8 | pages = 1471–14881471–88 | date = 2020-09-17 | pmid = 32942969 | doi = 10.2174/0929867327999200917150652 | s2cid = 221789280 }}</ref><ref name="BakerGT">{{cite journal | vauthors = Baker GT, Sprott RL | title = Biomarkers of aging | journal = Experimental Gerontology | volume = 23 | issue = 4–5 | pages = 223–39 | year = 1988 | pmid = 3058488 | doi = 10.1016/0531-5565(88)90025-3 | s2cid = 31039588 | url = https://zenodo.org/record/1258547 | access-date = 12 July 2019 | archive-date = 24 October 2021 | archive-url = https://web.archive.org/web/20211024064308/https://zenodo.org/record/1258547 | url-status = live }}</ref> However, [[Human hair color#Gray and white hair|graying of hair]],<ref>{{cite journal | vauthors = Van Neste D, Tobin DJ | title = Hair cycle and hair pigmentation: dynamic interactions and changes associated with aging | journal = Micron | volume = 35 | issue = 3 | pages = 193–200 | year = 2004 | pmid = 15036274 | doi = 10.1016/j.micron.2003.11.006 }}</ref> [[Face#Other characteristics|face aging]], [[wrinkle|skin wrinkles]] and other common changes seen with aging are not better indicators of future functionality than chronological age. [[Gerontology#Biogerontology|Biogerontologists]] have continued efforts to find and validate biomarkers of aging, but success thus far has been limited.

There is research and development of further biomarkers, detection systems and software systems to measure biological age of different tissues or systems or overall. For example, a [[deep learning]] (DL) software using anatomic [[magnetic resonance image]]s estimated [[brain aging|brain age]] with relatively high accuracy, including detecting early signs of Alzheimer's disease and varying [[neuroanatomical]] patterns of neurological aging,<ref>{{cite journal |last1=Yin |first1=Chenzhong |last2=Imms |first2=Phoebe |last3=Cheng |first3=Mingxi |display-authors=et al. |title=Anatomically interpretable deep learning of brain age captures domain-specific cognitive impairment |journal=Proceedings of the National Academy of Sciences |date=10 January 2023 |volume=120 |issue=2 |pages=e2214634120 |doi=10.1073/pnas.2214634120 |pmid=36595679 |pmc=9926270 |bibcode=2023PNAS..12014634Y |language=en |issn=0027-8424 }}

* University press release: {{cite news |title=How old is your brain, really? AI-powered analysis accurately reflects risk of cognitive decline and Alzheimer's disease |url=https://medicalxpress.com/news/2023-01-brain-ai-powered-analysis-accurately-cognitive.html |access-date=17 February 2023 |work=University of Southern California via medicalxpress.com |language=en |archive-date=17 February 2023 |archive-url=https://web.archive.org/web/20230217232042/https://medicalxpress.com/news/2023-01-brain-ai-powered-analysis-accurately-cognitive.html |url-status=live }}

* News article about the study: {{cite news |title=KI kann wahres Alter des Hirns bestimmen |url=https://www.deutschlandfunknova.de/nachrichten/alterungsprozess-ki-kann-wahres-alter-des-hirns-bestimmen |access-date=17 February 2023 |work=[[Deutschlandfunk Nova]] |language=de |archive-date=17 February 2023 |archive-url=https://web.archive.org/web/20230217232037/https://www.deutschlandfunknova.de/nachrichten/alterungsprozess-ki-kann-wahres-alter-des-hirns-bestimmen |url-status=live }}</ref> and a DL tool was reported as to calculate a person's [[Inflammaging|inflammatory age]] based on patterns of systemic age-related inflammation.<ref>{{cite journal |last1=Sayed |first1=Nazish |last2=Huang |first2=Yingxiang |last3=Nguyen |first3=Khiem |last4=Krejciova-Rajaniemi |first4=Zuzana |last5=Grawe |first5=Anissa P. |last6=Gao |first6=Tianxiang |last7=Tibshirani |first7=Robert |last8=Hastie |first8=Trevor |last9=Alpert |first9=Ayelet |last10=Cui |first10=Lu |last11=Kuznetsova |first11=Tatiana |last12=Rosenberg-Hasson |first12=Yael |last13=Ostan |first13=Rita |last14=Monti |first14=Daniela |last15=Lehallier |first15=Benoit |last16=Shen-Orr |first16=Shai S. |last17=Maecker |first17=Holden T. |last18=Dekker |first18=Cornelia L. |last19=Wyss-Coray |first19=Tony |last20=Franceschi |first20=Claudio |last21=Jojic |first21=Vladimir |last22=Haddad |first22=François |last23=Montoya |first23=José G. |last24=Wu |first24=Joseph C. |last25=Davis |first25=Mark M. |last26=Furman |first26=David |title=An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging |journal=Nature Aging |date=July 2021 |volume=1 |issue=7 |pages=598–615 |doi=10.1038/s43587-021-00082-y |pmid=34888528 |pmc=8654267 |language=en |issn=2662-8465|doi-access=free }}

* News article about the study: {{cite news |title=Tool that calculates immune system age could predict frailty and disease |url=https://newatlas.com/science/stanford-immune-system-age-biomarker-blood-test/ |access-date=26 July 2021 |work=New Atlas |date=13 July 2021 |archive-date=26 July 2021 |archive-url=https://web.archive.org/web/20210726110032/https://newatlas.com/science/stanford-immune-system-age-biomarker-blood-test/ |url-status=live }}</ref>

Aging clocks have been used to evaluate impacts of interventions on humans, including [[combination therapy|combination therapies]].<ref>{{cite journal |title=Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial |journal=Aging |year=2021 |pmid=33844651 |url=https://www.aging-us.com/article/202913/text |access-date=28 June 2021 |last1=Fitzgerald |first1=K. N. |last2=Hodges |first2=R. |last3=Hanes |first3=D. |last4=Stack |first4=E. |last5=Cheishvili |first5=D. |last6=Szyf |first6=M. |last7=Henkel |first7=J. |last8=Twedt |first8=M. W. |last9=Giannopoulou |first9=D. |last10=Herdell |first10=J. |last11=Logan |first11=S. |last12=Bradley |first12=R. |volume=13 |issue=7 |pages=9419–94329419–32 |doi=10.18632/aging.202913 |pmc=8064200 |archive-date=2 June 2021 |archive-url=https://web.archive.org/web/20210602114006/https://www.aging-us.com/article/202913/text |url-status=live }}</ref>{{additional citation needed|date=March 2023}} Exmploying aging clocks to identify and evaluate longevity interventions represents a fundamental goal in aging biology research. However, achieving this goal requires overcoming numerous challenges and implementing additional validation steps.<ref>{{Cite journal |last1=Moqri |first1=Mahdi |last2=Herzog |first2=Chiara |last3=Poganik |first3=Jesse R. |last4=Justice |first4=Jamie |last5=Belsky |first5=Daniel W. |last6=Higgins-Chen |first6=Albert |last7=Moskalev |first7=Alexey |last8=Fuellen |first8=Georg |last9=Cohen |first9=Alan A. |last10=Bautmans |first10=Ivan |last11=Widschwendter |first11=Martin |last12=Ding |first12=Jingzhong |last13=Fleming |first13=Alexander |last14=Mannick |first14=Joan |last15=Han |first15=Jing-Dong Jackie |date=August 2023 |title=Biomarkers of aging for the identification and evaluation of longevity interventions |url=https://doi.org/10.1016/j.cell.2023.08.003 |journal=Cell |volume=186 |issue=18 |pages=3758–75 |doi=10.1016/j.cell.2023.08.003 |pmid=37657418 |pmc=11088934 }}</ref><ref>{{Cite journal |last1=Moqri |first1=Mahdi |last2=Herzog |first2=Chiara |last3=Poganik |first3=Jesse R. |last4=Ying |first4=Kejun |last5=Justice |first5=Jamie N. |last6=Belsky |first6=Daniel W. |last7=Higgins-Chen |first7=Albert T. |last8=Chen |first8=Brian H. |last9=Cohen |first9=Alan A. |last10=Fuellen |first10=Georg |last11=Hägg |first11=Sara |last12=Marioni |first12=Riccardo E. |last13=Widschwendter |first13=Martin |last14=Fortney |first14=Kristen |last15=Fedichev |first15=Peter O. |date=February 2024 |title=Validation of biomarkers of aging |journal=Nature Medicine |volume=30 |issue=2 |pages=360–372 |doi=10.1038/s41591-023-02784-9 |issn=1546-170X |pmid=38355974|pmc=11090477 }}</ref>

The ability to repair DNA double-strand breaks declines with aging in mice<ref name="pmid25033455">{{cite journal |vauthors=Vaidya A, Mao Z, Tian X, Spencer B, Seluanov A, Gorbunova V |title=Knock-in reporter mice demonstrate that DNA repair by non-homologous end joining declines with age |journal=PLOS Genet. |volume=10 |issue=7 |pages=e1004511 |date=July 2014 |pmid=25033455 |pmc=4102425 |doi=10.1371/journal.pgen.1004511 |doi-access=free }}</ref> and humans.<ref name="pmid27391797">{{cite journal |vauthors=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 |title=Impaired DNA double-strand break repair contributes to the age-associated rise of genomic instability in humans |doi-access=free |journal=Cell Death Differ. |volume=23 |issue=11 |pages=1765–77 |date=November 2016 |pmid=27391797 |pmc=5071568 |doi=10.1038/cdd.2016.65 }}</ref>

A set of rare hereditary ([[genetics]]) disorders, each called [[progeria]], has been known for some time. Sufferers exhibit symptoms resembling [[Accelerated aging disease|accelerated aging]], including [[wrinkle|wrinkled skin]]. The cause of [[Progeria|Hutchinson–Gilford progeria syndrome]] was reported in the journal ''[[Nature (journal)|Nature]]'' in May 2003.<ref>{{cite journal | vauthors = Mounkes LC, Kozlov S, Hernandez L, Sullivan T, Stewart CL | title = A progeroid syndrome in mice is caused by defects in A-type lamins | journal = Nature | volume = 423 | issue = 6937 | pages = 298–301 | date = May 2003 | pmid = 12748643 | doi = 10.1038/nature01631 | s2cid = 4360055 | bibcode = 2003Natur.423..298M | url = https://zenodo.org/record/1233263 |via=Zenodo |s2cid-access=free | access-date = 21 July 2021 | archive-date = 30 May 2022 | archive-url = https://web.archive.org/web/20220530212807/https://zenodo.org/record/1233263 | url-status = live }}</ref>

A study indicates that aging may shift activity toward short genes or shorter transcript length and that this can be countered by interventions.<ref>{{cite journal |last1=Stoeger |first1=Thomas |last2=Grant |first2=Rogan A. |last3=McQuattie-Pimentel |first3=Alexandra C. |last4=Anekalla |first4=Kishore R. |last5=Liu |first5=Sophia S. |last6=Tejedor-Navarro |first6=Heliodoro |last7=Singer |first7=Benjamin D. |last8=Abdala-Valencia |first8=Hiam |last9=Schwake |first9=Michael |last10=Tetreault |first10=Marie-Pier |last11=Perlman |first11=Harris |last12=Balch |first12=William E. |last13=Chandel |first13=Navdeep S. |last14=Ridge |first14=Karen M. |last15=Sznajder |first15=Jacob I. |last16=Morimoto |first16=Richard I. |last17=Misharin |first17=Alexander V. |last18=Budinger |first18=G. R. Scott |last19=Nunes Amaral |first19=Luis A. |title=Aging is associated with a systemic length-associated transcriptome imbalance |journal=Nature Aging |date=December 2022 |volume=2 |issue=12 |pages=1191–1206 |doi=10.1038/s43587-022-00317-6 |pmid=37118543 |pmc=10154227 |language=en |issn=2662-8465|doi-access=free}}

* University press release: {{cite news |title=Aging is driven by unbalanced genes, finds AI analysis of multiple species |url=https://phys.org/news/2022-12-aging-driven-unbalanced-genes-ai.html |access-date=18 January 2023 |work=[[Northwestern University]] |via=phys.org |date=December 9, 2022 |archive-date=2 February 2023 |archive-url=https://web.archive.org/web/20230202173100/https://phys.org/news/2022-12-aging-driven-unbalanced-genes-ai.html |languageurl-status=enlive }}

* News article about the study: {{cite news |last1=Kwon |first1=Diana |title=Aging Is Linked to More Activity in Short Genes Than in Long Genes |url=https://www.scientificamerican.com/article/aging-is-linked-to-more-activity-in-short-genes-than-in-long-genes/ |url-access=subscription |date=January 6, 2023 |access-date=18 January 2023 |work=Scientific American |languagearchive-date=en17 January 2023 |archive-url=https://web.archive.org/web/20230117052143/https://www.scientificamerican.com/article/aging-is-linked-to-more-activity-in-short-genes-than-in-long-genes/ |url-status=live }}</ref>

[[File:Global aging demographics.webp|thumb|Past and projected age of the human world population through time as of 2021<ref name="10.1038/s41536-021-00169-5">{{cite journal |last1=Garmany |first1=Armin |last2=Yamada |first2=Satsuki |last3=Terzic |first3=Andre |title=Longevity leap: mind the healthspan gap |journal=npj Regenerative Medicine |date=23 September 2021 |volume=6 |issue=1 |page=57 |doi=10.1038/s41536-021-00169-5 |pmid=34556664 |pmc=8460831 |language=en |issn=2057-3995|doi-access=free}}

* Non-profit hospital press release: {{cite news |first1=Susan |last1=Buckles |title=A regenerative reset for aging » Center for Regenerative Biotherapeutics |url=https://regenerativemedicineblog.mayoclinic.org/2021/10/07/a-regenerative-reset-for-aging |date=October 7, 2021 |access-date=1 March 2023 |work=[[Mayo Clinic]] |archive-date=1 March 2023 |archive-url=https://web.archive.org/web/20230301172642/https://regenerativemedicineblog.mayoclinic.org/2021/10/07/a-regenerative-reset-for-aging/ |url-status=live }}</ref>]]

Many measures that may extend lifespans may simultaneously also extend healthspans, albeit that is not necessarily the case, indicating that "lifespan can no longer be the sole parameter of interest" in related research.<ref>{{cite journal |last1=Bansal |first1=Ankita |last2=Zhu |first2=Lihua J. |last3=Yen |first3=Kelvin |last4=Tissenbaum |first4=Heidi A. |title=Uncoupling lifespan and healthspan in Caenorhabditis elegans longevity mutants |journal=Proceedings of the National Academy of Sciences |date=20 January 2015 |volume=112 |issue=3 |pages=E277-86 |doi=10.1073/pnas.1412192112 |pmid=25561524 |pmc=4311797 |bibcode=2015PNAS..112E.277B |language=en |issn=0027-8424|doi-access=free }}</ref> While recent life expectancy increases were not followed by "parallel" healthspan expansion,<ref name="10.1038/s41536-021-00169-5"/> awareness of the concept and issues of healthspan lags as of 2017.<ref name="importance">{{cite web |title=Healthspan is more important than lifespan, so why don't more people know about it? {{!}}|url=https://publichealth.wustl.edu/heatlhspan-is-more-important-than-lifespan-so-why-dont-more-people-know-about-it/ |work=Institute for Public Health {{!}} |publisher=Washington University in St. Louis |date=May 30, 2017 |first1=Tim |last1=Peterson |agency=Harvey A. Friedman Center for Aging |access-date=1 March 2023 |archive-date=1 March 2023 |archive-url=https://web.archive.org/web/20230301172634/https://publichealth.wustl.edu/heatlhspan-is-more-important-than-lifespan-so-why-dont-more-people-know-about-it/ |website=publichealth.wustl.edu |accessurl-datestatus=1live March 2023}}</ref> Scientists have noted that "[[Aging-associated diseases|[c]hronic diseases of aging]] are increasing and are inflicting untold costs on human quality of life".<ref name="10.1016/j.tcb.2016.05.002">{{cite journal |last1=Hansen |first1=Malene |last2=Kennedy |first2=Brian K. |title=Does Longer Lifespan Mean Longer Healthspan? |journal=Trends in Cell Biology |date=1 August 2016 |volume=26 |issue=8 |pages=565–568565–8 |doi=10.1016/j.tcb.2016.05.002 |pmid=27238421 |pmc=4969078 |language=English |issn=0962-8924}}</ref>

{{Excerpt|Life extension}}{{Further|Life extension}}