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We therefore compared functional and accelerated aging in generally healthy adults with and without incident invasive cancer, using data from DO-HEALTH, a three-year, randomized controlled trial including 2152 participants (mean age: 74.9 years, 61.1% women), free of major health conditions. Functional aging was assessed by the Short Physical Performance Battery, handgrip strength, gait speed, and five-times sit-to-stand test (STS). Biological aging was measured in a subsample (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009777) using Horvath, Hannum, GrimAge and PhenoAge clocks, and DunedinPACE. Participants with incident cancer showed a greater decline in STS (\u0394 adjusted means [AM]: 0.64\u2009s [95% CI 0.06, 1.22]) and grip strength (\u0394AM \u22121.77\u2009kPa [\u22123.51, \u22120.03]). Furthermore, baseline biological aging was accelerated between 3.52 and 6.77 months, measured by Horvath, Hannum, and PhenoAge clocks. Findings support the geroscience hypothesis linking greater phenotypic functional decline to accelerated biological aging in older adults with incident cancer. The data for this observational analysis stem from the DO-HEALTH clinical trial, which was prospectively registered (clinicaltrials.gov; NCT01745263; registered on December 10, 2012).\n                  <\/jats:p>","DOI":"10.1038\/s41514-026-00360-2","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T11:35:33Z","timestamp":1774265733000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trajectories of physical function and biological aging in generally healthy older adults with and without incident invasive cancer over a three-year follow-up: findings from the DO-HEALTH study"],"prefix":"10.1038","volume":"12","author":[{"given":"Wiebke","family":"R\u00f6sler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Kistler-Fischbacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"G\u00e4ngler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus G.","family":"Manz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kressig W.","family":"Reto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Orav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bess","family":"Dawson-Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W.","family":"Belsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Horvath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter C.","family":"Willett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Wieczorek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike A.","family":"Bischoff-Ferrari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"360_CR1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/ijc.31664","volume":"144","author":"S Pilleron","year":"2019","unstructured":"Pilleron, S. et al. 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BMC Genomics 25, 798 (2024).","journal-title":"BMC Genomics"}],"container-title":["npj Aging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41514-026-00360-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41514-026-00360-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41514-026-00360-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:11:34Z","timestamp":1784797894000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41514-026-00360-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["360"],"URL":"https:\/\/doi.org\/10.1038\/s41514-026-00360-2","relation":{},"ISSN":["2731-6068"],"issn-type":[{"value":"2731-6068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]},"assertion":[{"value":"15 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"RWK declares funding for the DO-HEALTH recruitment site in Basel from the European Union to the University of Basel, honoraria for lectures and presentations at congresses and he is an editorial board member of the Journal of the American Geriatrics Society (JAGS) and Aging Clinical Experimental Research (ACER). DWB declares the following funding with payments to Columbia University: The MyGoals for Healthy Aging Multi-Center Randomized Controlled Trial (R01AG073402), Testing effects of cash transfers on biological aging and risk for Alzheimer\u2019s Disease (R01AG087158), Genetic analysis of the Dutch Hunger Winter Families Study to Boost Rigour and Robustness for Testing In-Utero Famine Effects on Aging-Related Health Conditions (R01AG066887) and Genomic analysis of the CALERIE\u2122 Trial to generate new knowledge for geroscience (R01AG061378). DWB further declares a TruDiagnostic License for DunedinPACE, consulting fees from BellSand for SAB Chairing and Consulting CSO role, and participation on the following boards: X-Prize Healthspan, CALERIE Research Network External Scientific Committee, Telomere Research Network SAB. SH is a founder and member of the non-profit Epigenetic Clock Development Foundation, which has licensed several patents for epigenetic clocks (including for GrimAge). HAB-F declares as the PI of DO-HEALTH, grants from the European Commission (Grant Agreement No. 278588), from the University of Zurich, from NESTEC, from PFIZER Consumer Healthcare, from Streuli Pharma, plus non-financial support from DSM Nutritional Products and from Roche Diagnostics. HAB-F further declares independent and investigator initiated grants from Pfizer and from Vifor, outside the submitted work and speaker fees from Wild, Pfizer, Vifor, Mylan, Roche Diagnostics. WR, MK-F, SG, MGM, EJO, BD-H, JR, WCW and MW declare no conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"99"}}