{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T06:53:58Z","timestamp":1793170438018,"version":"4.5.0"},"reference-count":217,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front Sci"],"abstract":"<jats:p>Evidence that drugs, diets, and single-gene mutations can slow aging and extend the healthy lifespan of mammals has begun to convert biogerontology from an observational science into one based on interventions that could provide people with additional years of healthy, productive life. However, the research and development of anti-aging drugs is hampered by the lack of instantaneous and continuous measures of the rate of aging itself. This article presents recent work on anti-aging drugs that are effective in mice, provides evidence for candidate \u201caging rate indicators\u201d (ARIs), and outlines a roadmap for translating these into clinical research to slow aging in humans. Thus far, 14 agents or combinations have significantly increased the lifespan of mice in studies conducted under the Interventions Testing Program (ITP) of the National Institute on Aging, often when initiated in late adulthood. Recent evidence suggests that many, perhaps all, interventions that slow aging in mice induce common, shared changes in physiological status and molecular pathways. We have proposed 12 such mechanisms as candidate ARIs, i.e., measurable outcomes that reflect a slow-aging state and that could discriminate between normal mice (and perhaps humans) and those exposed to effective anti-aging interventions\u2014thereby accelerating research. Research priorities now include testing the robustness of these ARIs, extending them to include plasma constituents, elucidating the mechanisms through which diverse interventions alter them, uncovering the links between the ARIs and late-life diseases, and extending research to dogs, non-human primates, and humans. The growing recognition of the legitimacy and promise of evidence-based interventions resulting from aging biology should elevate this field to a level of urgency and respect comparable to that of current research on individual age-related conditions.<\/jats:p>","DOI":"10.3389\/fsci.2026.1821393","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:59:28Z","timestamp":1789635568000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Aging rate indicators and the search for anti-aging drugs"],"prefix":"10.3389","volume":"4","author":[{"given":"Steven N.","family":"Austad","sequence":"first","affiliation":[{"name":"Department of Biology, University of Alabama at Birmingham","place":["Birmingham, AL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Kaeberlein","sequence":"additional","affiliation":[{"name":"Optispan, Inc.","place":["Seattle, WA, United States"]},{"name":"Dog Aging Institute","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pathology and Geriatrics Center, University of Michigan","place":["Ann Arbor, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","volume-title":"The retardation of aging and disease by dietary restriction","author":"Weindruch","year":"1988"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/123.2.269","article-title":"Low methionine ingestion by rats extends life span","volume":"123","author":"Orentreich","year":"1993","journal-title":"J Nutr"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00744-7","article-title":"Late-life protein or isoleucine restriction impacts physiological and molecular signatures of aging","volume":"4","author":"Yeh","year":"2024","journal-title":"Nat Aging"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/384033a0","article-title":"Dwarf mice and the ageing process","volume":"384","author":"Brown-Borg","year":"1996","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2007.00328.x","article-title":"Loss of pregnancy-associated plasma protein A extends lifespan in mice","volume":"6","author":"Conover","year":"2007","journal-title":"Aging Cell"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111158898","article-title":"Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production","volume":"98","author":"Flurkey","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.7.7586","article-title":"Assessment of growth parameters and life span of GHR\/BP gene-disrupted mice","volume":"141","author":"Coschigano","year":"2000","journal-title":"Endocrinology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.02.001","article-title":"Pten positively regulates brown adipose function, energy expenditure, and longevity","volume":"15","author":"Ortega-Molina","year":"2012","journal-title":"Cell Metab"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nature08221","article-title":"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice","volume":"460","author":"Harrison","year":"2009","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12170","article-title":"Acarbose, 17-alpha-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males","volume":"13","author":"Harrison","year":"2014","journal-title":"Aging Cell"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.140019","article-title":"Canagliflozin extends life span in genetically heterogeneous male but not female mice","volume":"5","author":"Miller","year":"2020","journal-title":"JCI Insight"},{"key":"B12","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-815962-0.00010-X","article-title":"NIA Interventions Testing Program: a collaborative approach for investigating interventions to promote healthy aging","volume-title":"Handbook of the biology of aging","author":"Macchiarini","year":"2021"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e12898","DOI":"10.1111\/acel.12898","article-title":"Acarbose improves health and lifespan in aging HET3 mice","volume":"18","author":"Harrison","year":"2019","journal-title":"Aging Cell"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-01011-0","article-title":"Astaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules used","volume":"46","author":"Harrison","year":"2023","journal-title":"Geroscience"},{"key":"B15","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1093\/jn\/10.1.63","article-title":"The effect of retarded growth upon the length of life span and upon the ultimate body size","volume":"10","author":"McCay","year":"1935","journal-title":"J Nutr"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199710023371407","article-title":"Caloric intake and aging","volume":"337","author":"Weindruch","year":"1997","journal-title":"N Engl J Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/geronj\/40.6.671","article-title":"Nutritional influences on aging of Fischer 344 rats: II. Pathology","volume":"40","author":"Maeda","year":"1985","journal-title":"J Gerontol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1985.248.4.E488","article-title":"Does food restriction retard aging by reducing the metabolic rate","volume":"248","author":"McCarter","year":"1985","journal-title":"Am J Physiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/0531-5565(89)90037-5","article-title":"Life extension by dietary restriction in the bowl and doily spider, Frontinella pyramitela","volume":"24","author":"Austad","year":"1989","journal-title":"Exp Gerontol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08026-3","article-title":"Dietary restriction impacts health and lifespan of genetically diverse mice","volume":"634","author":"Di Francesco","year":"2024","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.exger.2016.03.011","article-title":"Calories or protein? The effect of dietary restriction on lifespan in rodents is explained by calories alone","volume":"86","author":"Speakman","year":"2016","journal-title":"Exp Gerontol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2011.12.006","article-title":"Dietary restriction in rats and mice: a meta-analysis and review of the evidence for genotype-dependent effects on lifespan","volume":"11","author":"Swindell","year":"2012","journal-title":"Ageing Res Rev"},{"key":"B23","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1007\/BF03324535","article-title":"The effects of different levels of dietary restriction on non-neoplastic diseases in male Sprague-Dawley rats","volume":"16","author":"Duffy","year":"2004","journal-title":"Aging Clin Exp Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/BF03340130","article-title":"Physical activity as a factor in the action of dietary restriction on aging: effects in Fischer 344 rats","volume":"9","author":"McCarter","year":"1997","journal-title":"Aging Clin Exp Res"},{"key":"B25","article-title":"Caloric restriction and chemical toxicity\/carcinogenesis","volume":"1","author":"Hart","year":"1992","journal-title":"Qual Assur"},{"key":"B26","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/978-1-4684-7953-9_7","article-title":"Modulation of chemical toxicity by modification of caloric intake","author":"Hart","year":"1992","journal-title":"Exercise, calories, fat and cancer. Advances in Experimental Medicine and Biology."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405499101","article-title":"Hyperleptinemia prevents lipotoxic cardiomyopathy in acyl CoA synthase transgenic mice","volume":"101","author":"Lee","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/60.6.688","article-title":"Caloric restriction decreases survival of aged mice in response to primary influenza infection","volume":"60","author":"Gardner","year":"2005","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1128\/cdli.8.5.1003-1011.2001","article-title":"Effects of calorie restriction on polymicrobial peritonitis induced by cecum ligation and puncture in young C57BL\/6 mice","volume":"8","author":"Sun","year":"2001","journal-title":"Clin Diagn Lab Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/geronj\/31.2.144","article-title":"Dietary protein, life-span, and biochemical variables in female mice","volume":"31","author":"Leto","year":"1976","journal-title":"J Gerontol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.73.4.1279","article-title":"Influence of diet on survival of mice","volume":"73","author":"Fernandes","year":"1976","journal-title":"Proc Natl Acad Sci USA"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/geronj\/33.2.184","article-title":"Body weight increment and length of life: the effect of genetic constitution and dietary protein","volume":"33","author":"Goodrick","year":"1978","journal-title":"J Gerontol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.cmet.2020.01.010","article-title":"The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice","volume":"31","author":"Solon-Biet","year":"2020","journal-title":"Cell Metab"},{"key":"B34","doi-asserted-by":"publisher","first-page":"3557","DOI":"10.1038\/ncomms4557","article-title":"Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys","volume":"5","author":"Colman","year":"2014","journal-title":"Nat Commun"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nature11432","article-title":"Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study","volume":"489","author":"Mattison","year":"2012","journal-title":"Nature"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14063","article-title":"Caloric restriction improves health and survival of rhesus monkeys","volume":"8","author":"Mattison","year":"2017","journal-title":"Nat Commun"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(19)30151-2","article-title":"2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial","volume":"7","author":"Kraus","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1089\/rej.2006.0529","article-title":"Long-term low-calorie low-protein vegan diet and endurance exercise are associated with low cardiometabolic risk","volume":"10","author":"Fontana","year":"2007","journal-title":"Rejuvenation Res"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308291101","article-title":"Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans","volume":"101","author":"Fontana","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"B40","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/S0531-5565(02)00149-3","article-title":"Nutritional control of aging","volume":"38","author":"Zimmerman","year":"2003","journal-title":"Exp Gerontol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2005.00152.x","article-title":"Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance","volume":"4","author":"Miller","year":"2005","journal-title":"Aging Cell"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glp051","article-title":"Life-span extension in mice by preweaning food restriction and by methionine restriction in middle age","author":"Sun","year":"2009","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1016\/j.cmet.2023.10.005","article-title":"Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice","volume":"35","author":"Green","year":"2023","journal-title":"Cell Metab"},{"key":"B44","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/0047-6374(88)90099-1","article-title":"Histology and survival in age-delayed low-tryptophan-fed rats","volume":"43","author":"Ooka","year":"1988","journal-title":"Mech Ageing Dev"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1126\/science.2392681","article-title":"Increased life-span of age-1 mutants in Caenorhabditis elegans and lower Gompertz rate of aging","volume":"249","author":"Johnson","year":"1990","journal-title":"Science"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/366461a0","article-title":"A C. elegans mutant that lives twice as long as wild-type","volume":"366","author":"Kenyon","year":"1993","journal-title":"Nature"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/366404a0","article-title":"Methuselah among nematodes","volume":"366","author":"Partridge","year":"1993","journal-title":"Nature"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glp017","article-title":"Reduced incidence and delayed occurrence of fatal neoplastic diseases in growth hormone receptor\/binding protein knockout mice","volume":"64","author":"Ikeno","year":"2009","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/58.4.B291","article-title":"Delayed occurrence of fatal neoplastic diseases in Ames dwarf mice: correlation to extended longevity","volume":"58","author":"Ikeno","year":"2003","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e01098","DOI":"10.7554\/eLife.01098","article-title":"Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice","volume":"2","author":"Sun","year":"2013","journal-title":"Elife"},{"key":"B51","article-title":"Use of genetic models to investigate the hypophyseal regulation of senescence","volume-title":"Genetic effects on aging II","author":"Flurkey","year":"1990"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2010.00630.x","article-title":"PAPP-A: a new anti-aging target","volume":"9","author":"Conover","year":"2010","journal-title":"Aging Cell"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-2086","article-title":"Liver-specific GH receptor gene-disrupted (LiGHRKO) mice have decreased endocrine IGF-I, increased local IGF-I, and altered body size, body composition, and adipokine profiles","volume":"155","author":"List","year":"2014","journal-title":"Endocrinology"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1690","article-title":"Regulation of mTOR activity in Snell dwarf and GH receptor gene-disrupted mice","volume":"156","author":"Dominick","year":"2015","journal-title":"Endocrinology"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-163253","article-title":"Early life growth hormone treatment shortens longevity and decreases cellular stress resistance in long-lived mutant mice","volume":"24","author":"Panici","year":"2010","journal-title":"FASEB J"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12382","article-title":"Growth hormone modulates hypothalamic inflammation in long-lived pituitary dwarf mice","volume":"14","author":"Sadagurski","year":"2015","journal-title":"Aging Cell"},{"key":"B57","doi-asserted-by":"publisher","first-page":"e22394","DOI":"10.1096\/fj.202200143R","article-title":"Transient early life growth hormone exposure permanently alters brain, muscle, liver, macrophage, and adipocyte status in long-lived Ames dwarf mice","volume":"36","author":"Li","year":"2022","journal-title":"FASEB J"},{"key":"B58","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1093\/gerona\/glq178","article-title":"Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice","volume":"66","author":"Miller","year":"2011","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12194","article-title":"Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction","volume":"13","author":"Miller","year":"2014","journal-title":"Aging Cell"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12496","article-title":"Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an alpha-glucosidase inhibitor or a Nrf2-inducer","volume":"15","author":"Strong","year":"2016","journal-title":"Aging Cell"},{"key":"B61","doi-asserted-by":"publisher","first-page":"e13724","DOI":"10.1111\/acel.13724","article-title":"Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice","volume":"21","author":"Strong","year":"2022","journal-title":"Aging Cell"},{"key":"B62","doi-asserted-by":"publisher","first-page":"e13328","DOI":"10.1111\/acel.13328","article-title":"17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex","volume":"20","author":"Harrison","year":"2021","journal-title":"Aging Cell"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-024-01176-2","article-title":"Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin","volume":"46","author":"Miller","year":"2025","journal-title":"Geroscience"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-022-00641-0","article-title":"Canagliflozin retards age-related lesions in heart, kidney, liver, and adrenal gland in genetically heterogenous male mice","volume":"45","author":"Snyder","year":"2022","journal-title":"Geroscience"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2008.00414.x","article-title":"Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice","volume":"7","author":"Strong","year":"2008","journal-title":"Aging Cell"},{"key":"B66","doi-asserted-by":"publisher","first-page":"e12953","DOI":"10.1111\/acel.12953","article-title":"Glycine supplementation extends lifespan of male and female mice","volume":"18","author":"Miller","year":"2019","journal-title":"Aging Cell"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-025-01881-6","article-title":"Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice","volume":"48","author":"Strong","year":"2025","journal-title":"Geroscience"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2004.07.003","article-title":"Statistical methods for testing effects on \"maximum lifespan","volume":"125","author":"Wang","year":"2004","journal-title":"Mech Ageing Dev"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2012.00861.x","article-title":"A comparative assessment of univariate longevity measures using zoological animal records","volume":"11","author":"Moorad","year":"2012","journal-title":"Aging Cell"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo5482","article-title":"Rapamycin treatment during development extends life span and health span of male mice and Daphnia magna","volume":"8","author":"Shindyapina","year":"2022","journal-title":"Sci Adv"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/59.10.B977","article-title":"Genetic loci that influence cause of death in a heterogeneous mouse stock","volume":"59","author":"Lipman","year":"2004","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2012.00832.x","article-title":"Rapamycin slows aging in mice","volume":"11","author":"Wilkinson","year":"2012","journal-title":"Aging Cell"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.06.054","article-title":"Chronic inhibition of mammalian target of rapamycin by rapamycin modulates cognitive and non-cognitive components of behavior throughout lifespan in mice","volume":"223","author":"Halloran","year":"2012","journal-title":"Neuroscience"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2011.00791.x","article-title":"Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL-1\u03b2 and enhancing NMDA signaling","volume":"11","author":"Majumder","year":"2012","journal-title":"Aging Cell"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glx249","article-title":"Short-term low-dose mTORC1 inhibition in aged rats counter-regulates age-related gene changes and blocks age-related kidney pathology","volume":"73","author":"Shavlakadze","year":"2018","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glv307","article-title":"Rapamycin attenuates age-associated changes in tibialis anterior tendon viscoelastic properties","volume":"71","author":"Zaseck","year":"2016","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B77","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s11357-019-00087-x","article-title":"Effect of caloric restriction and rapamycin on ovarian aging in mice","volume":"41","author":"Garcia","year":"2019","journal-title":"Geroscience"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.658972","article-title":"Rapamycin added to diet in late mid-life delays age-related hearing loss in UMHET4 mice","volume":"15","author":"Altschuler","year":"2021","journal-title":"Front Cell Neurosci"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1038\/nature11163","article-title":"mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake","volume":"486","author":"Yilmaz","year":"2012","journal-title":"Nature"},{"key":"B80","doi-asserted-by":"publisher","first-page":"e16351","DOI":"10.7554\/eLife.16351","article-title":"Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice","volume":"5","author":"Bitto","year":"2016","journal-title":"eLife"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12109","article-title":"Late-life rapamycin treatment reverses age-related heart dysfunction","volume":"12","author":"Flynn","year":"2013","journal-title":"Aging Cell"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12203","article-title":"Altered proteome turnover and remodeling by short-term caloric restriction or rapamycin rejuvenate the aging heart","volume":"13","author":"Dai","year":"2014","journal-title":"Aging Cell"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000559","article-title":"mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells","volume":"2","author":"Chen","year":"2009","journal-title":"Sci Signal"},{"key":"B84","doi-asserted-by":"publisher","first-page":"e54318","DOI":"10.7554\/eLife.54318","article-title":"Rapamycin rejuvenates oral health in aging mice","volume":"9","author":"An","year":"2020","journal-title":"eLife"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12590","article-title":"Anti-aging drugs reduce hypothalamic inflammation in a sex-specific manner","volume":"16","author":"Sadagurski","year":"2017","journal-title":"Aging Cell"},{"key":"B86","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1093\/gerona\/glac221","article-title":"Early or late-life treatment with acarbose or rapamycin improves physical performance and affects cardiac structure in aging mice","volume":"78","author":"Herrera","year":"2023","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B87","doi-asserted-by":"publisher","first-page":"e13747","DOI":"10.1172\/jci.insight.137474","article-title":"Acarbose has sex-dependent and -independent effects on age-related physical function, cardiac health, and lipid biology","volume":"5","author":"Herrera","year":"2020","journal-title":"JCI Insight"},{"key":"B88","doi-asserted-by":"publisher","first-page":"e12920","DOI":"10.1111\/acel.12920","article-title":"17-alpha estradiol ameliorates age-associated sarcopenia and improves late-life physical function in male mice but not in females or castrated males","volume":"18","author":"Garratt","year":"2019","journal-title":"Aging Cell"},{"key":"B89","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.cmet.2019.06.018","article-title":"Identification and application of gene expression signatures associated with lifespan extension","volume":"30","author":"Tyshkovskiy","year":"2019","journal-title":"Cell Metab"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-00917-z","article-title":"Proteomic changes induced by longevity-promoting interventions in mice","volume":"46","author":"Burns","year":"2024","journal-title":"Geroscience"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.59368\/agingbio.20230003","article-title":"Aging rate indicators: speedometers for aging research in mice","author":"Miller","year":"2023","journal-title":"Aging Biol"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-024-01466-9","article-title":"Downregulation of the NF-\u03baB protein p65 is a shared phenotype among most anti-aging interventions","volume":"47","author":"ElMansi","year":"2025","journal-title":"Geroscience"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-00770-0","article-title":"Four anti-aging drugs and calorie-restricted diet produce parallel effects in fat, brain, muscle, macrophages, and plasma of young mice","volume":"45","author":"Li","year":"2023","journal-title":"Geroscience"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-01025-8","article-title":"Recapitulation of anti-aging phenotypes by global overexpression of PTEN in mice","volume":"46","author":"Hager","year":"2023","journal-title":"Geroscience"},{"key":"B95","doi-asserted-by":"publisher","first-page":"e13685","DOI":"10.1111\/acel.13685","article-title":"Cap-independent translation of GPLD1 enhances markers of brain health in long-lived mutant and drug-treated mice","volume":"21","author":"Li","year":"2022","journal-title":"Aging Cell"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-022-00692-3","article-title":"Recapitulation of anti-aging phenotypes by global, but not by muscle-specific, deletion of PAPP-A in mice","volume":"45","author":"Li","year":"2022","journal-title":"Geroscience"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121904","article-title":"Canagliflozin shares common mTOR and MAPK signaling mechanisms with other lifespan extension treatments","volume":"328","author":"Jiang","year":"2023","journal-title":"Life Sci"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-022-00264-1","article-title":"Rapamycin, acarbose and 17alpha-estradiol share common mechanisms regulating the MAPK pathways involved in intracellular signaling and inflammation","volume":"19","author":"Wink","year":"2022","journal-title":"Immun Ageing"},{"key":"B99","doi-asserted-by":"publisher","first-page":"e13345","DOI":"10.1111\/acel.13345","article-title":"Cap-independent translation: a shared mechanism for lifespan extension by rapamycin, acarbose, and 17alpha-estradiol","volume":"20","author":"Shen","year":"2021","journal-title":"Aging Cell"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1530\/JME-19-0021","article-title":"Cap-independent mRNA translation is upregulated in long-lived endocrine mutant mice","volume":"63","author":"Ozkurede","year":"2019","journal-title":"J Mol Endocrinol"},{"key":"B101","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1111\/acel.12525","article-title":"mTOR regulates the expression of DNA damage response enzymes in long-lived Snell dwarf, GHRKO, and PAPP-A KO mice","volume":"16","author":"Dominick","year":"2017","journal-title":"Aging Cell"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103380","article-title":"Muscle-dependent regulation of adipose tissue function in long-lived growth hormone-mutant mice","volume":"12","author":"Li","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw2622","article-title":"Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain","volume":"369","author":"Horowitz","year":"2020","journal-title":"Science"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.797581","article-title":"Early life interventions can shape aging","volume":"13","author":"Bartke","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2006.06.005","article-title":"Statistical analysis regarding the effects of height and weight on life span of the domestic dog","volume":"82","author":"Greer","year":"2007","journal-title":"Res Vet Sci"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2013.09.020","article-title":"Longevity and mortality of owned dogs in England","volume":"198","author":"O'Neill","year":"2013","journal-title":"Vet J"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2024.100774","article-title":"Multi-discrimination exposure and biological aging: results from the Midlife in the United States Study","volume":"39","author":"Cuevas","year":"2024","journal-title":"Brain Behav Immun Health"},{"key":"B108","doi-asserted-by":"publisher","first-page":"e73420","DOI":"10.7554\/eLife.73420","article-title":"DunedinPACE, a DNA methylation biomarker of the pace of aging","volume":"11","author":"Belsky","year":"2022","journal-title":"eLife"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-025-00866-6","article-title":"Pace of Aging analysis of healthspan and lifespan in older adults in the US and UK","volume":"5","author":"Balachandran","year":"2025","journal-title":"Nat Aging"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1111\/iep.12228","article-title":"Ageing is associated with brown adipose tissue remodelling and loss of white fat browning in female C57BL\/6 mice","volume":"98","author":"Goncalves","year":"2017","journal-title":"Int J Exp Pathol"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12010","article-title":"Aging leads to a programmed loss of brown adipocytes in murine subcutaneous white adipose tissue","volume":"11","author":"Rogers","year":"2012","journal-title":"Aging Cell"},{"key":"B112","doi-asserted-by":"publisher","first-page":"e13032","DOI":"10.1111\/acel.13032","article-title":"Skewed macrophage polarization in aging skeletal muscle","volume":"18","author":"Cui","year":"2019","journal-title":"Aging Cell"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312940","article-title":"Age-dependent shift in macrophage polarisation causes inflammation-mediated degeneration of enteric nervous system","volume":"67","author":"Becker","year":"2018","journal-title":"Gut"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.2337\/db15-0502","article-title":"Rapamycin blocks induction of the thermogenic program in white adipose tissue","volume":"65","author":"Tran","year":"2016","journal-title":"Diabetes"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1038\/srep37223","article-title":"mTORC1 is required for brown adipose tissue recruitment and metabolic adaptation to cold","volume":"6","author":"Labbe","year":"2016","journal-title":"Sci Rep"},{"key":"B116","doi-asserted-by":"publisher","first-page":"e124","DOI":"10.1093\/nar\/gkaa878","article-title":"signatureSearch: environment for gene expression signature searching and functional interpretation","volume":"48","author":"Duan","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1101\/gr.275672.121","article-title":"Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart","volume":"32","author":"Gerdes Gyuricza","year":"2022","journal-title":"Genome Res"},{"key":"B118","doi-asserted-by":"publisher","first-page":"e62585","DOI":"10.7554\/eLife.62585","article-title":"Proteomic and transcriptomic profiling reveal different aspects of aging in the kidney","volume":"10","author":"Takemon","year":"2021","journal-title":"Elife"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112715","article-title":"Global and tissue-specific aging effects on murine proteomes","volume":"42","author":"Keele","year":"2023","journal-title":"Cell Rep"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1101\/2023.02.28.530532","article-title":"Autonomous AI agents discover aging interventions from millions of molecular profiles","author":"Ying","year":"2025"},{"key":"B121","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1038\/s42003-023-05128-y","article-title":"Lifespan-extending interventions induce consistent patterns of fatty acid oxidation in mouse livers","volume":"6","author":"Watanabe","year":"2023","journal-title":"Commun Biol"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-025-02028-3","article-title":"Discrimination of normal from slow-aging mice by plasma metabolomic and proteomic features","author":"Badenoch","year":"2025","journal-title":"Geroscience"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/S1046-2023(03)00050-1","article-title":"Genome-wide RNAi screening in Caenorhabditis elegans","volume":"30","author":"Kamath","year":"2003","journal-title":"Methods"},{"key":"B124","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/ng1140","article-title":"C. elegans ORFeome version 1.1: experimental verification of the genome annotation and resource for proteome-scale protein expression","volume":"34","author":"Reboul","year":"2003","journal-title":"Nat Genet"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1126\/science.1077780","article-title":"Rates of behavior and aging specified by mitochondrial function during development","volume":"298","author":"Dillin","year":"2002","journal-title":"Science"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1038\/ng1056","article-title":"A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity","volume":"33","author":"Lee","year":"2003","journal-title":"Nat Genet"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1308205","article-title":"A systematic RNAi screen for longevity genes in C. elegans","volume":"19","author":"Hamilton","year":"2005","journal-title":"Genes Dev"},{"key":"B128","doi-asserted-by":"publisher","first-page":"e17","DOI":"10.1371\/journal.pgen.0010017","article-title":"New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen","volume":"1","author":"Hansen","year":"2005","journal-title":"PloS Genet"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1101\/gr.074724.107","article-title":"Quantitative evidence for conserved longevity pathways between divergent eukaryotic species","volume":"18","author":"Smith","year":"2008","journal-title":"Genome Res"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a025114","article-title":"Biochemical genetic pathways that modulate aging in multiple species","volume":"5","author":"Bitto","year":"2015","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13740","article-title":"Genetics of human longevity: from variants to genes to pathways","volume":"295","author":"Smulders","year":"2024","journal-title":"J Intern Med"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.04.007","article-title":"TOR signaling and rapamycin influence longevity by regulating SKN-1\/Nrf and DAF-16\/FoxO","volume":"15","author":"Robida-Stubbs","year":"2012","journal-title":"Cell Metab"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4222","article-title":"Cardioprotection and lifespan extension by the natural polyamine spermidine","volume":"22","author":"Eisenberg","year":"2016","journal-title":"Nat Med"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1975","article-title":"Induction of autophagy by spermidine promotes longevity","volume":"11","author":"Eisenberg","year":"2009","journal-title":"Nat Cell Biol"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4132","article-title":"Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents","volume":"22","author":"Ryu","year":"2016","journal-title":"Nat Med"},{"key":"B136","doi-asserted-by":"publisher","first-page":"2192","DOI":"10.1038\/ncomms3192","article-title":"Metformin improves healthspan and lifespan in mice","volume":"4","author":"Martin-Montalvo","year":"2013","journal-title":"Nat Commun"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf2693","article-title":"NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice","volume":"352","author":"Zhang","year":"2016","journal-title":"Science"},{"key":"B138","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.cmet.2020.08.004","article-title":"Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice","volume":"32","author":"Asadi Shahmirzadi","year":"2020","journal-title":"Cell Metab"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-00867-6","article-title":"The million-molecule challenge: a moonshot project to rapidly advance longevity intervention discovery","volume":"45","author":"Lee","year":"2023","journal-title":"Geroscience"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1126\/science.1173635","article-title":"Caloric restriction delays disease onset and mortality in rhesus monkeys","volume":"325","author":"Colman","year":"2009","journal-title":"Science"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101340","article-title":"The development of a specific pathogen free (SPF) barrier colony of marmosets (Callithrix jacchus) for aging research","volume":"9","author":"Ross","year":"2017","journal-title":"Aging (Albany NY)"},{"key":"B142","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1093\/ilar.52.1.54","article-title":"The marmoset as a model of aging and age-related diseases","volume":"52","author":"Tardif","year":"2011","journal-title":"ILAR J"},{"key":"B143","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/s0149-7634(01)00064-1","article-title":"Non-human primate models for investigating fear and anxiety","volume":"26","author":"Barros","year":"2002","journal-title":"Neurosci Biobehav Rev"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2024.105655","article-title":"The fortunes and misfortunes of social life across the life course: a new era of research from field, laboratory and comparative studies","volume":"162","author":"Bartolomucci","year":"2024","journal-title":"Neurosci Biobehav Rev"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.3402\/pba.v6.31793","article-title":"Pharmaceutical inhibition of mTOR in the common marmoset: effect of rapamycin on regulators of proteostasis in a non-human primate","volume":"6","author":"Lelegren","year":"2016","journal-title":"Pathobiol Aging Age Relat Dis"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glu101","article-title":"Testing efficacy of administration of the antiaging drug rapamycin in a nonhuman primate, the common marmoset","volume":"70","author":"Tardif","year":"2015","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-021-00438-7","article-title":"DNA methylation age analysis of rapamycin in common marmosets","volume":"43","author":"Horvath","year":"2021","journal-title":"Geroscience"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1101\/2024.05.14.594256","article-title":"Inhibition of mTORC1 by rapamycin results in feedback activation of Akt(S473) and aggravates hallmarks of osteoarthritis in female mice and non-human primates","author":"Minton","year":"2025"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-024-01311-z","article-title":"A pilot study evaluating dosing tolerability of 17alpha-estradiol in male common marmosets (Callithrix jacchus)","volume":"47","author":"Sathiaseelan","year":"2025","journal-title":"Geroscience"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a026633","article-title":"The companion dog as a model for the longevity dividend","volume":"6","author":"Creevy","year":"2016","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.77.12.1357","article-title":"Assessment of frailty in aged dogs","volume":"77","author":"Hua","year":"2016","journal-title":"Am J Vet Res"},{"key":"B152","doi-asserted-by":"publisher","first-page":"16749","DOI":"10.1038\/s41598-019-52585-9","article-title":"A frailty index based on clinical data to quantify mortality risk in dogs","volume":"9","author":"Banzato","year":"2019","journal-title":"Sci Rep"},{"key":"B153","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1086\/669665","article-title":"The size-life span trade-off decomposed: why large dogs die young","volume":"181","author":"Kraus","year":"2013","journal-title":"Am Nat"},{"key":"B154","doi-asserted-by":"publisher","DOI":"10.1007\/s10592-019-01240-x","article-title":"Body size, inbreeding, and lifespan in domestic dogs","volume":"21","author":"Yordy","year":"2020","journal-title":"Conserv Genet"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-016-9638-7","article-title":"The Dog Aging Project: translational geroscience in companion animals","volume":"27","author":"Kaeberlein","year":"2016","journal-title":"Mamm Genome"},{"key":"B156","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04282-9","article-title":"Dog Aging Project Consortium. An open science study of ageing in companion dogs","volume":"602","author":"Creevy","year":"2022","journal-title":"Nature"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-025-01571-3","article-title":"Rationale and design of the Dog Aging Project precision cohort: a multi-omic resource for longitudinal research in geroscience","volume":"47","author":"Prescott","year":"2025","journal-title":"Geroscience"},{"key":"B158","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-017-9972-z","article-title":"A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs","volume":"39","author":"Urfer","year":"2017","journal-title":"Geroscience"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2023.1168711","article-title":"A masked, placebo-controlled, randomized clinical trial evaluating safety and the effect on cardiac function of low-dose rapamycin in 17 healthy client-owned dogs","volume":"10","author":"Barnett","year":"2023","journal-title":"Front Vet Sci"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-024-01484-7","article-title":"Test of Rapamycin in Aging Dogs (TRIAD): study design and rationale for a prospective, parallel-group, double-masked, randomized, placebo-controlled, multicenter trial of rapamycin in healthy middle-aged dogs from the Dog Aging Project","volume":"47","author":"Coleman","year":"2025","journal-title":"Geroscience"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/59.6.B523","article-title":"Anti-aging medicine and research: a realm of conflict and profound societal implications","volume":"59","author":"Binstock","year":"2004","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B162","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1093\/geront\/43.1.4","article-title":"The war on \"anti-aging medicine","volume":"43","author":"Binstock","year":"2003","journal-title":"Gerontologist"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-018-0042-y","article-title":"A framework for selection of blood-based biomarkers for geroscience-guided clinical trials: report from the TAME Biomarkers Workgroup","volume":"40","author":"Justice","year":"2018","journal-title":"Geroscience"},{"key":"B164","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnha.2025.100637","article-title":"Advancing geroscience research \u2013 a scoping review of regulatory environments for gerotherapeutics","volume":"29","author":"Muscedere","year":"2025","journal-title":"J Nutr Health Aging"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1297.098","article-title":"Immortal ethics","volume":"1019","author":"Harris","year":"2004","journal-title":"Ann N Y Acad Sci"},{"key":"B166","doi-asserted-by":"publisher","DOI":"10.1111\/bioe.12600","article-title":"Should I want to live to 100","volume":"33","author":"Pence","year":"2019","journal-title":"Bioethics"},{"key":"B167","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/hast.5007","article-title":"Why we can thrive past seventy-five: in favor of efforts to extend the human lifespan","volume":"55","author":"Ringel","year":"2025","journal-title":"Hastings Cent Rep"},{"key":"B168","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1297.099","article-title":"Collective suttee: is it unjust to develop life extension if it will not be possible to provide it to everyone","volume":"1019","author":"Davis","year":"2004","journal-title":"Ann N Y Acad Sci"},{"key":"B169","first-page":"37","article-title":"A biologist's perspective: whence come we, where are we, whither go we","volume-title":"Enduring questions and changing perspectives in gerontology","author":"Austad","year":"2005"},{"key":"B170","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-021-00080-0","article-title":"The economic value of targeting aging","volume":"1","author":"Scott","year":"2021","journal-title":"Nat Aging"},{"key":"B171","doi-asserted-by":"publisher","DOI":"10.1377\/hlthaff.2013.0052","article-title":"Substantial health and economic returns from delayed aging may warrant a new focus for medical research","volume":"32","author":"Goldman","year":"2013","journal-title":"Health Aff (Millwood)"},{"key":"B172","first-page":"28","article-title":"In pursuit of the longevity dividend","volume-title":"The Scientist","author":"Olshansky","year":"2006"},{"key":"B173","volume-title":"The longevity imperative","author":"Scott","year":"2024"},{"key":"B174","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-00818-1","article-title":"Evaluation of off-label rapamycin use to promote healthspan in 333 adults","volume":"45","author":"Kaeberlein","year":"2023","journal-title":"Geroscience"},{"key":"B175","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.05.011","article-title":"Metformin as a tool to target aging","volume":"23","author":"Barzilai","year":"2016","journal-title":"Cell Metab"},{"key":"B176","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2025.102817","article-title":"Emerging uncertainty on the anti-aging potential of metformin","volume":"111","author":"Keys","year":"2025","journal-title":"Ageing Res Rev"},{"key":"B177","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyac200","article-title":"Reassessing the evidence of a survival advantage in Type 2 diabetes treated with metformin compared with controls without diabetes: a retrospective cohort study","volume":"51","author":"Keys","year":"2022","journal-title":"Int J Epidemiol"},{"key":"B178","doi-asserted-by":"publisher","DOI":"10.1001\/jama.294.16.2086","article-title":"Provision or distribution of growth hormone for \u201cqantiaging\u201d: clinical and legal issues","volume":"294","author":"Perls","year":"2005","journal-title":"JAMA"},{"key":"B179","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: an expanding universe","volume":"186","author":"L\u00f3pez-Ot\u00edn","year":"2023","journal-title":"Cell"},{"key":"B180","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"L\u00f3pez-Ot\u00edn","year":"2013","journal-title":"Cell"},{"key":"B181","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of cancer: new dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov"},{"key":"B182","doi-asserted-by":"publisher","DOI":"10.1126\/science.3299702","article-title":"Human aging: usual and successful","volume":"237","author":"Rowe","year":"1987","journal-title":"Science"},{"key":"B183","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32130-X","article-title":"Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories 1990\u20132016: a systematic analysis for the Global Burden of Disease Study 2016","volume":"390","year":"2017","journal-title":"Lancet"},{"key":"B184","first-page":"1","article-title":"Deaths: final data for 2000","volume":"50","author":"Mini\u00f1o","year":"2002","journal-title":"Natl Vital Stat Rep"},{"key":"B185","doi-asserted-by":"crossref","DOI":"10.15620\/cdc:106058","article-title":"Deaths: final data for 2019","volume-title":"Natl Vital Stat Rep","author":"Xu","year":"2021"},{"key":"B186","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00580-3","article-title":"Cancer-related accelerated ageing and biobehavioural modifiers: a framework for research and clinical care","volume":"19","author":"Carroll","year":"2022","journal-title":"Nat Rev Clin Oncol"},{"key":"B187","doi-asserted-by":"publisher","DOI":"10.1038\/nature05354","article-title":"Resveratrol improves health and survival of mice on a high-calorie diet","volume":"444","author":"Baur","year":"2006","journal-title":"Nature"},{"key":"B188","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.cmet.2018.02.001","article-title":"Nicotinamide improves aspects of healthspan, but not lifespan, in mice","volume":"27","author":"Mitchell","year":"2018","journal-title":"Cell Metab"},{"key":"B189","doi-asserted-by":"publisher","DOI":"10.2460\/javma.2001.218.669","article-title":"2000 report of the AVMA panel on euthanasia","volume":"218","year":"2001","journal-title":"J Am Vet Med Assoc"},{"key":"B190","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1412192112","article-title":"Uncoupling lifespan and healthspan in Caenorhabditis elegans longevity mutants","volume":"112","author":"Bansal","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"B191","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.03.062","article-title":"How a mutation that slows aging can also disproportionately extend end-of-life decrepitude","volume":"19","author":"Podshivalova","year":"2017","journal-title":"Cell Rep"},{"key":"B192","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/0014-4827(61)90192-6","article-title":"The serial cultivation of human diploid cell strains","volume":"25","author":"Hayflick","year":"1961","journal-title":"Exp Cell Res"},{"key":"B193","doi-asserted-by":"publisher","DOI":"10.1038\/345458a0","article-title":"Telomeres shorten during ageing of human fibroblasts","volume":"345","author":"Harley","year":"1990","journal-title":"Nature"},{"key":"B194","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5349.349","article-title":"Extension of life-span by introduction of telomerase into normal human cells [see comments","volume":"279","author":"Bodnar","year":"1998","journal-title":"Science"},{"key":"B195","volume-title":"Science and sanity: an introduction to non-Aristotelian systems and general semantics","author":"Korzybski","year":"1933"},{"key":"B196","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.11.2950","article-title":"Disease states associated with telomerase deficiency appear earlier in mice with short telomeres","volume":"18","author":"Herrera","year":"1999","journal-title":"EMBO J"},{"key":"B197","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.05.015","article-title":"Senescence in cancer","volume":"43","author":"Colucci","year":"2025","journal-title":"Cancer Cell"},{"key":"B198","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00483-8","article-title":"The metabolic roots of senescence: mechanisms and opportunities for intervention","volume":"3","author":"Wiley","year":"2021","journal-title":"Nat Metab"},{"key":"B199","doi-asserted-by":"publisher","first-page":"e301","DOI":"10.1371\/journal.pbio.0060301","article-title":"Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor","volume":"6","author":"Copp\u00e9","year":"2008","journal-title":"PloS Biol"},{"key":"B200","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.20.9363","article-title":"A biomarker that identifies senescent human cells in culture and in aging skin in vivo","volume":"92","author":"Dimri","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"B201","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.05.059","article-title":"Guidelines for minimal information on cellular senescence experimentation in vivo","volume":"187","author":"Ogrodnik","year":"2024","journal-title":"Cell"},{"key":"B202","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-025-02314-y","article-title":"Advancing biological understanding of cellular senescence with computational multiomics","volume":"57","author":"Li","year":"2025","journal-title":"Nat Genet"},{"key":"B203","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1146\/annurev-pharmtox-050120-105018","article-title":"Senolytic drugs: reducing senescent cell viability to extend health span","volume":"61","author":"Robbins","year":"2021","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"B204","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.cell.2012.01.003","article-title":"Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock","volume":"148","author":"Rando","year":"2012","journal-title":"Cell"},{"key":"B205","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00738-8","article-title":"SenNet recommendations for detecting senescent cells in different tissues","volume":"25","author":"Suryadevara","year":"2024","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B206","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27185925","article-title":"Senescent phenotype of astrocytes leads to activation of BV2 microglia and N2a neuronal cells death","volume":"27","author":"Zhang","year":"2022","journal-title":"Molecules"},{"key":"B207","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.cmet.2019.05.006","article-title":"Acceleration of beta cell aging determines diabetes and senolysis improves disease outcomes","volume":"30","author":"Aguayo-Mazzucato","year":"2019","journal-title":"Cell Metab"},{"key":"B208","doi-asserted-by":"publisher","DOI":"10.1038\/s41514-025-00312-2","article-title":"Do we actually need aging clocks","volume":"12","author":"Kriukov","year":"2025","journal-title":"NPJ Aging"},{"key":"B209","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14103604","article-title":"Epigenetic clocks and EpiScore for preventive medicine: risk stratification and intervention models for age-related diseases","volume":"14","author":"Yamada","year":"2025","journal-title":"J Clin Med"},{"key":"B210","doi-asserted-by":"publisher","DOI":"10.1001\/amajethics.2025.828","article-title":"What are the most ethically salient implications of epigenetic age testing","volume":"27","author":"Hauskeller","year":"2025","journal-title":"AMA J Ethics"},{"key":"B211","volume-title":"Supplements and influencers, a dangerous combination","author":"Proenca","year":"2024"},{"key":"B212","doi-asserted-by":"publisher","DOI":"10.1111\/1468-0009.00006","article-title":"Extending life: scientific prospects and political obstacles","volume":"80","author":"Miller","year":"2002","journal-title":"Milbank Q"},{"key":"B213","volume-title":"Why buy more time?","author":"Lynch","year":"1999"},{"key":"B214","volume-title":"Why I hope to die at 75","author":"Emanuel","year":"2014"},{"key":"B215","doi-asserted-by":"publisher","DOI":"10.1126\/science.2237414","article-title":"In search of Methuselah: estimating the upper limits to human longevity","volume":"250","author":"Olshansky","year":"1990","journal-title":"Science"},{"key":"B216","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5508.1491","article-title":"Prospects for human longevity","volume":"291","author":"Olshansky","year":"2001","journal-title":"Science"},{"key":"B217","unstructured":"Living to 120 and beyond: Americans' views on aging, medical advances and radical life extension [online]\n          \n          \n          \n          2013"}],"container-title":["Frontiers in Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsci.2026.1821393\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:28:27Z","timestamp":1789716507000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsci.2026.1821393\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":217,"alternative-id":["10.3389\/fsci.2026.1821393"],"URL":"https:\/\/doi.org\/10.3389\/fsci.2026.1821393","relation":{},"ISSN":["2813-6330"],"issn-type":[{"value":"2813-6330","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"article-number":"1821393"}}