Editing Longevity (section)

==Major factors==
Evidence-based studies indicate that longevity is based on two major factors: [[genetics]] and [[Lifestyle (social sciences)|lifestyle]].<ref name=USC>{{Cite news | vauthors = Marziali C |date=7 December 2010 |title=Reaching Toward the Fountain of Youth |url=http://uscnews.usc.edu/health/reaching_toward_the_fountain_of_youth.html |work=USC Trojan Family Magazine |access-date=7 December 2010 |archive-url=https://web.archive.org/web/20101213203112/http://uscnews.usc.edu/health/reaching_toward_the_fountain_of_youth.html |archive-date=13 December 2010 }}</ref>

===Genetics===
{{Further|Genetics of aging}}
[[Twin study|Twin studies]] have estimated that approximately 20-30% of the variation in human lifespan can be related to [[genetics]], with the rest due to individual behaviors and [[environmental factor]]s which can be modified.<ref>{{cite journal | vauthors = vB Hjelmborg J, Iachine I, Skytthe A, Vaupel JW, McGue M, Koskenvuo M, Kaprio J, Pedersen NL, Christensen K | display-authors = 6 | title = Genetic influence on human lifespan and longevity | journal = Human Genetics | volume = 119 | issue = 3 | pages = 312–321 | date = April 2006 | pmid = 16463022 | doi = 10.1007/s00439-006-0144-y | s2cid = 8470835 }}</ref> Although over 200 gene variants have been associated with longevity according to a US-Belgian-UK research database of human genetic variants<ref>{{Cite web|title=LongevityMap|url=http://genomics.senescence.info/longevity/|access-date=2013-09-23|work=Human Ageing Genomic Resources|publisher=senescence.info by [[João Pedro de Magalhães]]|date=n.d.|archive-date=2013-09-21|archive-url=https://web.archive.org/web/20130921223946/http://genomics.senescence.info/longevity/|url-status=live}}</ref> these explain only a small fraction of the heritability.<ref>{{cite journal | vauthors = Budovsky A, Craig T, Wang J, Tacutu R, Csordas A, Lourenço J, Fraifeld VE, de Magalhães JP | display-authors = 6 | title = LongevityMap: a database of human genetic variants associated with longevity | journal = Trends in Genetics | volume = 29 | issue = 10 | pages = 559–560 | date = October 2013 | pmid = 23998809 | doi = 10.1016/j.tig.2013.08.003 }}</ref>

[[Lymphoblast]]oid cell lines established from blood samples of [[centenarians]] have significantly higher activity of the DNA repair protein PARP ([[Poly ADP ribose polymerase]]) than cell lines from younger (20 to 70 year old) individuals.<ref name="pmid9587069">{{cite journal | vauthors = Muiras ML, Müller M, Schächter F, Bürkle A | title = Increased poly(ADP-ribose) polymerase activity in lymphoblastoid cell lines from centenarians | journal = Journal of Molecular Medicine | volume = 76 | issue = 5 | pages = 346–354 | date = April 1998 | pmid = 9587069 | doi = 10.1007/s001090050226 | s2cid = 24616650 }}</ref> The lymphocytic cells of centenarians have characteristics typical of cells from young people, both in their capability of priming the mechanism of repair after {{chem2|link=Hydrogen peroxide|H2O2}} sublethal [[DNA oxidation|oxidative DNA damage]] and in their PARP gene expression.<ref name="pmid17518695">{{cite journal | vauthors = Chevanne M, Calia C, Zampieri M, Cecchinelli B, Caldini R, Monti D, Bucci L, Franceschi C, Caiafa P | display-authors = 6 | title = Oxidative DNA damage repair and parp 1 and parp 2 expression in Epstein-Barr virus-immortalized B lymphocyte cells from young subjects, old subjects, and centenarians | journal = Rejuvenation Research | volume = 10 | issue = 2 | pages = 191–204 | date = June 2007 | pmid = 17518695 | doi = 10.1089/rej.2006.0514 }}</ref> These findings suggest that elevated PARP gene expression contributes to the longevity of centenarians, consistent with the [[DNA damage theory of aging]].<ref>{{cite book |vauthors=Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K  |chapter=1. Cancer and aging as consequences of un-repaired DNA damage |chapter-url=https://www.novapublishers.com/catalog/product_info.php?products_id=43247  |editor-first=Honoka |editor-last=Kimura |editor2-first=Aoi |editor2-last=Suzuki |title=New Research on DNA Damages  |publisher=[[Nova Science Publishers, Inc.]] |date=2008 |isbn=978-1-60456-581-2 |pages=1–47 |oclc=213848806}}</ref>

[[File:Healthspan, parental lifespan, and longevity are highly genetically correlated.webp|thumb|upright 1.3|"Healthspan, parental lifespan, and longevity are highly genetically correlated."<ref name="Multivariate"/>]]
In July [[2020 in science|2020]], scientists used public [[List of biological databases|biological data]] on 1.75 m people with known lifespans overall and identified 10 [[Locus (genetics)|genomic loci]] which appear to intrinsically influence [[healthspan]], lifespan, and longevity – of which half have not been reported previously at [[Genome-wide association study|genome-wide significance]] and most being associated with [[cardiovascular disease]] – and identified [[Human iron metabolism|haem metabolism]] as a promising candidate for further research within the field. Their study suggests that high levels of iron in the blood likely reduce, and genes involved in metabolising iron likely increase healthy years of life in humans.<ref name="ironmeta">{{cite news |title=Blood iron levels could be key to slowing ageing, gene study shows |url=https://phys.org/news/2020-07-blood-iron-key-ageing-gene.html |access-date=18 August 2020 |work=phys.org |language=en |archive-date=16 March 2022 |archive-url=https://web.archive.org/web/20220316201154/https://phys.org/news/2020-07-blood-iron-key-ageing-gene.html |url-status=live }}</ref><ref name="Multivariate">{{cite journal |vauthors=Timmers PR, Wilson JF, Joshi PK, Deelen J |date=July 2020 |title=Multivariate genomic scan implicates novel loci and haem metabolism in human ageing |journal=Nature Communications |volume=11 |issue=1 |pages=3570 |bibcode=2020NatCo..11.3570T |doi=10.1038/s41467-020-17312-3 |pmc=7366647 |pmid=32678081 |doi-access=free}}</ref>

=== Lifestyle ===
Longevity is a highly plastic trait, and traits that influence its components respond to physical (static) environments and to wide-ranging life-style changes: physical exercise, dietary habits, living conditions, and pharmaceutical as well as nutritional interventions.<ref>{{cite journal | vauthors = Govindaraju D, Atzmon G, Barzilai N | title = Genetics, lifestyle and longevity: Lessons from centenarians | journal = Applied & Translational Genomics | volume = 4 | pages = 23–32 | date = March 2015 | pmid = 26937346 | pmc = 4745363 | doi = 10.1016/j.atg.2015.01.001 }}</ref><ref>{{cite journal | vauthors = Passarino G, De Rango F, Montesanto A | title = Human longevity: Genetics or Lifestyle? It takes two to tango | journal = Immunity & Ageing | volume = 13 | issue = 1 | pages = 12 | date = 2016-04-05 | pmid = 27053941 | pmc = 4822264 | doi = 10.1186/s12979-016-0066-z | doi-access = free }}</ref><ref>{{cite journal | vauthors = Dato S, Rose G, Crocco P, Monti D, Garagnani P, Franceschi C, Passarino G | title = The genetics of human longevity: an intricacy of genes, environment, culture and microbiome | journal = Mechanisms of Ageing and Development | volume = 165 | issue = Pt B | pages = 147–155 | date = July 2017 | pmid = 28390822 | doi = 10.1016/j.mad.2017.03.011 | s2cid = 13654470 }}</ref> A 2012 study found that even modest amounts of leisure time physical exercise can extend life expectancy by as much as 4.5 years.<ref>{{cite journal | vauthors = Moore SC, Patel AV, Matthews CE, Berrington de Gonzalez A, Park Y, Katki HA, Linet MS, Weiderpass E, Visvanathan K, Helzlsouer KJ, Thun M, Gapstur SM, Hartge P, Lee IM | display-authors = 6 | title = Leisure time physical activity of moderate to vigorous intensity and mortality: a large pooled cohort analysis | journal = PLOS Medicine | volume = 9 | issue = 11 | pages = e1001335 | year = 2012 | pmid = 23139642 | pmc = 3491006 | doi = 10.1371/journal.pmed.1001335 | doi-access = free }}</ref> 

==== Diet ====
As of 2021, there is no [[evidence-based medicine|clinical evidence]] that any dietary practice contributes to human longevity.<ref name="lee">{{cite journal |vauthors=Lee MB, Hill CM, Bitto A, Kaeberlein M |date=November 2021 |title=Antiaging diets: Separating fact from fiction |journal=Science |volume=374 |issue=6570 |pages=eabe7365 |doi=10.1126/science.abe7365 |pmc=8841109 |pmid=34793210}}</ref> Although health can be influenced by diet, including the type of foods consumed, the amount of calories ingested, and the duration and frequency of fasting periods,<ref>{{Cite journal |last1=Longo |first1=Valter D. |last2=Anderson |first2=Rozalyn M. |date=2022 |title=Nutrition, longevity and disease: From molecular mechanisms to interventions |journal=Cell |language=en |volume=185 |issue=9 |pages=1455–1470 |doi=10.1016/j.cell.2022.04.002|pmid=35487190 |pmc=9089818 }}</ref> there is no good clinical evidence that fasting promotes longevity in humans, {{As of|2021|lc=y}}.<ref name=lee/><ref name=":1" /><ref>{{Cite web | url=https://simple.life/blog/intermittent-fasting-benefits/ |title = Intermittent Fasting Schedules |date = 26 January 2023 }}</ref>

Calorie restriction is a widely researched intervention to assess effects on aging, defined as a sustained reduction in dietary energy intake compared to the energy required for weight maintenance.<ref name=lee/><ref name=":1" /> To ensure metabolic [[homeostasis]], the diet during calorie restriction must provide sufficient energy, micronutrients, and fiber.<ref name=":1">{{Cite journal |last1=Flanagan |first1=Emily W. |last2=Most |first2=Jasper |last3=Mey |first3=Jacob T. |last4=Redman |first4=Leanne M. |date=2020-09-23 |title=Calorie restriction and aging in humans |journal=Annual Review of Nutrition |language=en |volume=40 |issue=1 |pages=105–133 |doi=10.1146/annurev-nutr-122319-034601 |pmid=32559388 |pmc=9042193 |issn=0199-9885}}</ref> Some studies on rhesus monkeys showed that restricting calorie intake resulted in lifespan extension, while other animals studies did not detect a significant change.<ref name="lee" /><ref>{{Cite journal|display-authors=3 |last1=Mattison |first1=Julie A. |last2=Colman |first2=Ricki J. |last3=Beasley |first3=T. Mark |last4=Allison |first4=David B. |last5=Kemnitz |first5=Joseph W. |last6=Roth |first6=George S. |last7=Ingram |first7=Donald K. |last8=Weindruch |first8=Richard |last9=de Cabo |first9=Rafael |last10=Anderson |first10=Rozalyn M. |date=2017-01-17 |title=Caloric restriction improves health and survival of rhesus monkeys |journal=Nature Communications |language=en |volume=8 |issue=1 |pages=14063 |doi=10.1038/ncomms14063 |pmid=28094793 |issn=2041-1723|pmc=5247583 |bibcode=2017NatCo...814063M }}</ref> According to preliminary research in humans, there is little evidence that calorie restriction affects lifespan.<ref name=lee/><ref name=":1" /> There is a link between [[diet and obesity]] and consequent [[obesity-associated morbidity]].

=== Biological pathways ===
Four well-studied [[biological pathway]]s that are known to regulate aging, and whose modulation has been shown to influence longevity are [[Insulin-like growth factor#IGF1/GH axis|Insulin/IGF-1]], mechanistic target of rapamycin ([[mTOR]]), AMP-activating protein kinase ([[AMP-activated protein kinase|AMPK]]), and [[Sirtuin]] pathways.<ref>{{cite journal | vauthors = Kenyon CJ | title = The genetics of ageing | journal = Nature | volume = 464 | issue = 7288 | pages = 504–512 | date = March 2010 | pmid = 20336132 | doi = 10.1038/nature08980 | s2cid = 2781311 | bibcode = 2010Natur.464..504K }}</ref><ref name=":0">{{cite journal | vauthors = Bareja A, Lee DE, White JP | title = Maximizing Longevity and Healthspan: Multiple Approaches All Converging on Autophagy | language = English | journal = Frontiers in Cell and Developmental Biology | volume = 7 | pages = 183 | date = 2019 | pmid = 31555646 | pmc = 6742954 | doi = 10.3389/fcell.2019.00183 | doi-access = free }}</ref>