{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:00:34Z","timestamp":1790236834517,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01NS069673"],"award-info":[{"award-number":["U01NS069673"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RF1NS139183"],"award-info":[{"award-number":["RF1NS139183"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Epigenetic clocks have emerged as markers of biological aging. Understanding their association with age-related functional decline may provide insights into DNA-mediated mechanisms underlying frailty-related functional decline and reveal which clocks best associate with accelerated functional decline. We therefore examined associations between established epigenetic clock measures and longitudinal trajectories of cognitive function, grip strength, and walking speed. We analyzed data from 4018 participants in the Health and Retirement Study with available DNA methylation data and up to 12\u2009years of follow-up data. Using linear mixed-effects models, we examined retrospective associations between 12 epigenetic clocks and longitudinal trajectories of frailty-related functional decline, modeling interactions between each epigenetic clock and time, adjusting for chronological age and sociodemographic covariates. In longitudinal analyses controlling for chronological age, older epigenetic age was associated with faster cognitive decline for Hannum (\u03b2\u2009=\u2009\u22120.0054, 95% CI, \u22120.0095 to \u22120.0014, p\u2009=\u2009.009) and DNAmGrimAge (\u03b2\u2009=\u2009\u22120.0141, 95% CI, \u22120.0174 to \u22120.0107, p\u2009&amp;lt;\u2009.001). Higher DNAmGrimAge was associated with accelerated decline in grip strength (\u03b2\u2009=\u2009\u22120.024, 95% CI, \u22120.033 to \u22120.015, p\u2009&amp;lt;\u2009.001) and decline in walking speed (\u03b2\u2009=\u2009\u22120.0008, 95% CI, \u22120.0013 to \u22120.0004, p\u2009&amp;lt;\u2009.001). Higher epigenetic clock biological age estimates, particularly DNAmGrimAge, are retrospectively associated with accelerated frailty-related functional decline across multiple functional domains. Systematic comparison of clock derivations may reveal specific epigenetic patterns underlying age-related functional deterioration.<\/jats:p>","DOI":"10.1093\/gerona\/glag213","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T16:47:31Z","timestamp":1787935651000},"source":"Crossref","is-referenced-by-count":0,"title":["Biological age associates with longitudinal frailty-related functional decline: the Health and Retirement Study"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7415-2566","authenticated-orcid":false,"given":"Savvina","family":"Prapiadou","sequence":"first","affiliation":[{"name":"Department of Neurology, Mass General Brigham , Boston, Massachusetts,","place":["United States"]},{"name":"Department of Neurology, Brain Care Labs, Mass General Brigham , Boston, Massachusetts,","place":["United States"]},{"name":"Center for Genomic Medicine, Massachusetts General Hospital , Boston, Massachusetts,","place":["United States"]},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard , Cambridge, Massachusetts,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara N","family":"Kimball","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham , Boston, Massachusetts,","place":["United States"]},{"name":"Department of Neurology, Brain Care Labs, Mass General Brigham , Boston, Massachusetts,","place":["United States"]},{"name":"Center for Genomic Medicine, Massachusetts General Hospital , Boston, Massachusetts,","place":["United States"]},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard , Cambridge, Massachusetts,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin Y Q","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham , Boston, Massachusetts,","place":["United States"]},{"name":"Department of Neurology, Brain Care Labs, Mass General Brigham , Boston, Massachusetts,","place":["United States"]},{"name":"Center for Genomic Medicine, Massachusetts General Hospital , Boston, Massachusetts,","place":["United States"]},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard , Cambridge, Massachusetts,","place":["United States"]},{"name":"Division of Neurology, Department of Medicine, National University Hospital ,","place":["Singapore"]},{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR) ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3204-0309","authenticated-orcid":false,"given":"Reinier W P","family":"Tack","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham , Boston, Massachusetts,","place":["United 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Brain Care Labs, Mass General Brigham , Boston, Massachusetts,","place":["United States"]},{"name":"Center for Genomic Medicine, Massachusetts General Hospital , Boston, Massachusetts,","place":["United States"]},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard , Cambridge, Massachusetts,","place":["United States"]},{"name":"Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht , Utrecht,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evy M","family":"Reinders","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham , Boston, Massachusetts,","place":["United States"]},{"name":"Department of Neurology, Brain Care Labs, Mass General Brigham , Boston, Massachusetts,","place":["United States"]},{"name":"Center for Genomic Medicine, Massachusetts General Hospital , Boston, Massachusetts,","place":["United States"]},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard , Cambridge, Massachusetts,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tan L","family":"Feng","sequence":"additional","affiliation":[{"name":"Healthy Ageing Programme, Alexandra Hospital, National University Health System ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjula D","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham , Boston, Massachusetts,","place":["United States"]},{"name":"Department of Neurology, Brain Care Labs, Mass General Brigham , Boston, Massachusetts,","place":["United States"]},{"name":"Center for Genomic Medicine, Massachusetts General Hospital , Boston, Massachusetts,","place":["United States"]},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard , Cambridge, Massachusetts,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Rosand","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham , Boston, Massachusetts,","place":["United States"]},{"name":"Department of Neurology, Brain Care Labs, Mass General Brigham , Boston, Massachusetts,","place":["United States"]},{"name":"Center for Genomic Medicine, Massachusetts General Hospital , Boston, Massachusetts,","place":["United States"]},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard , Cambridge, Massachusetts,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham , Boston, Massachusetts,","place":["United States"]},{"name":"Department of Neurology, Brain Care Labs, Mass General Brigham , Boston, 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