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We tested whether somatic mutations in the blood were associated with incident frailty and faster progression in 730,088 participants from UK Biobank, All of Us, BioVU and the Women\u2019s Health Initiative. We found that clonal hematopoiesis of indeterminate potential (CHIP) and autosomal mosaic chromosomal alterations showed strong associations with frailty, whereas mosaic loss of chromosome X or Y did not. Findings were consistent across survey-based, directly measured and clinically assessed frailty, as well as healthspan phenotypes. A\n                  <jats:italic>Tet2<\/jats:italic>\n                  mouse model demonstrated multisystem frailty-like functional decline and T-cell remodeling. In humans, T-cell activation-related proteins directly mediated the association between clonal hematopoiesis and frailty. Collectively, these findings support a model in which clonal hematopoiesis accelerates biological aging through immunosenescence.\n                <\/jats:p>","DOI":"10.64898\/2026.09.24.26363888","type":"posted-content","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:20:21Z","timestamp":1790886021000},"source":"Crossref","is-referenced-by-count":0,"title":["Clonal Hematopoiesis Accelerates Frailty and Functional Decline"],"prefix":"10.64898","author":[{"given":"Kun","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"name":"Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candice","family":"Quin","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Victoria University of Wellington, NZ"},{"name":"Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yash","family":"Pershad","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"name":"Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"name":"Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhi","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"name":"Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace I","family":"Bowman","sequence":"additional","affiliation":[{"name":"Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA"},{"name":"Department of Ecology and Evolutionary Biology, University of Colorado Boulder, Boulder, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlyn","family":"Vlasschaert","sequence":"additional","affiliation":[{"name":"Department of Medicine, Queen\u2019s University, Kingston, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6787-9051","authenticated-orcid":false,"given":"Robert W","family":"Corty","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Brett","family":"Heimlich","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica N","family":"DeJong","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Health Sciences, McMaster University, Canada"},{"name":"Firestone Institute for Respiratory Health, St. Joseph\u2019s Healthcare Hamilton, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Queen\u2019s University, Kingston, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zil","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Queen\u2019s University, Kingston, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco 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