ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2026
Epigenetic clocks of biological aging and cognitively healthy longevity: the Women's Health Initiative Memory Study.
Andrea Z LaCroix, Bowei Zhang, Steve Nguyen, Susan M Resnick, Luigi Ferrucci, Steve Horvath, Ake T Lu, Mark A Espeland, Stephen R Rapp, Kenneth Beckman and 4 more
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In one paragraphArticle in The journals of gerontology. Series A, Biological sciences and medical sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
14 authors.
Andrea Z LaCroixHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, San Diego, California, United States.ORCID 0000-0002-9532-976X Bowei ZhangHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, San Diego, California, United States.ORCID 0009-0000-9686-0897 Steve NguyenHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, San Diego, California, United States.ORCID 0000-0002-5193-7042 Susan M ResnickLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States.
Luigi FerrucciLongitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland, United States.ORCID 0000-0002-6273-1613 Steve HorvathDivision of Geriatrics, Department of Medicine, University of California Los Angeles, Los Angeles, California, United States.
Ake T LuAltos Labs, San Diego, California, United States.
Mark A EspelandDivision of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States.ORCID 0000-0002-3711-1949 Stephen R RappDepartment of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States.
Kenneth BeckmanGenomics Center, University of Minnesota, Minneapolis, Minnesota, United States.
Caroline NievergeltDepartment of Psychiatry School of Medicine, University of California San Diego, San Diego, California, United States.
Adam X MaihoferDepartment of Psychiatry School of Medicine, University of California San Diego, San Diego, California, United States.
Linda K McEvoyKaiser Permanente Washington Health Research Institute, Seattle, Washington, United States.ORCID 0000-0003-4583-7798 Aladdin H ShadyabHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, San Diego, California, United States.
Funding
WOMEN'S HEALTH INITIATIVE - CLINICAL COORDINATING CENTER: TASK AREA B - LONG LIFE STUDY VISIT 2 LIMITED HOME VISIT75N92021D00001 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ANDERSON, GARNET L. · 2021 to 2025
$52.0MSedentary Behaviour Interrupted: Acute, medium and long-term effects on biomarkers of healthy aging, physical function and mortalityP01AG052352 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LACROIX, ANDREA Z. · 2017 to 2022
$9.0MWOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC): TASK AREA A AND A275N92021D00002 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI WACTAWSKI-WENDE, JEAN · 2021 to 2025
$6.9MWOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00004 · NHLBI · STANFORD UNIVERSITY · PI STEFANICK, MARCIA · 2021 to 2025
$6.5MWOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00003 · NHLBI · OHIO STATE UNIVERSITY · PI JACKSON, REBECCA · 2021 to 2025
$5.0MWOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00005 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI VITOLINS, MARA · 2021 to 2025
$4.2MPlasma proteomic signatures of physical activity and Alzheimer's disease and related dementiasK99AG082863 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NGUYEN, STEVE · 2023 to 2024
$206kNational Institute on Aging, National Institutes of Health 03-cv-2496NHLBI NIH HHS 75N92021D00001NHLBI NIH HHS 75N92021D00002NIA NIH HHS 1K99AG082863-02NIA NIH HHS K99 AG082863NIA NIH HHS P01 AG052352US Department of Health and Human Services 75N92021D00001US Department of Health and Human Services 75N92021D00002US Department of Health and Human Services 75N92021D00003US Department of Health and Human Services 75N92021D00004US Department of Health and Human Services 75N92021D00005WHI NIH HHS 75N92021D00003WHI NIH HHS 75N92021D00004WHI NIH HHS 75N92021D00005
6 · The paper itselfAbstract
backgroundLittle is known about whether epigenetic age acceleration (EAA) clocks are capable of predicting exceptional longevity with or without preserved cognitive function.
methodsWe examined 5844 women from the Women's Health Initiative Memory Study. Fifteen epigenetic clocks were measured at baseline (1996-1999). Longevity outcomes were defined as (1) survival to age 90 with preserved cognition (n = 1726, 29.5%) or (2) survival to age 90 with cognitive impairment (n = 956, 16.4%); vs (3) death before age 90 (n = 2611, 44.7%). Logistic regression models examined associations between the 15 clocks and survival to age 90 (vs death before age 90), adjusting for covariates. Multinomial logistic regression models examined associations with survival to age 90 without cognitive impairment and survival to age 90 with cognitive impairment (each vs death before age 90), also adjusting for covariates.
resultsEach standard deviation increase in EAA for the first-generation clocks was associated with 7%-18% reduced odds of survival to age 90 vs earlier death. Stronger associations were observed for second- and third-generation clocks, including AgeAccelGrim2 (odds ratio [OR] = 0.66; 95% CI 0.61-0.71), PCGrimAge (OR = 0.64; 95% CI 0.59-0.69), PCPhenoAge (OR = 0.73; 95% CI 0.68-0.78), and DunedinPACE (OR = 0.77; 95% CI 0.72-0.82). None of the clocks was more strongly associated with survival to age 90 with preserved cognition than with survival to age 90 with cognitive impairment, relative to death before age 90.
conclusionsAll epigenetic clocks were associated with exceptional longevity, but none were associated with cognitive healthspan. Developing clocks that can differentiate long survival with and without preserved cognitive function is critical.
Indexed as
AgingCognitionEpigenesis, GeneticHealthy AgingLongevityAgedAged, 80 and overFemaleHumansLogistic ModelsWomen's HealthBrain functionHealthspanHealthy aging
Identifiers
PMID42679383
PMCPMC13641828
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