{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:56:48Z","timestamp":1790391408885,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T00:00:00Z","timestamp":1748044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Program of Natural Science Fund of China","award":["82373683"],"award-info":[{"award-number":["82373683"]}]},{"name":"Program of Natural Science Fund of China","award":["CFH 2024-1G-4261"],"award-info":[{"award-number":["CFH 2024-1G-4261"]}]},{"name":"Capital\u2019s Funds for Health Improvement and Research","award":["82373683"],"award-info":[{"award-number":["82373683"]}]},{"name":"Capital\u2019s Funds for Health Improvement and Research","award":["CFH 2024-1G-4261"],"award-info":[{"award-number":["CFH 2024-1G-4261"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objectives: Previous studies have confirmed that biological age (BA) acceleration is associated with single cardio-renal\u2013metabolic diseases (CRMDs), typically including type 2 diabetes mellitus, cardiovascular disease, and chronic kidney disease. However, its association with progression to cardio-renal\u2013metabolic multimorbidity (CRMM, coexistence of \u22652 CRMDs) and subsequent mortality remains unexplored. Methods: Using the multi-state model, we analyzed 278,927 UK Biobank participants free of CRMDs at baseline to investigate the association between BA acceleration\u2014measured by phenotypic age (PhenoAge) and Klemera\u2013Doubal method age (KDMAge)\u2014and CRMM progression trajectory, from health to the first CRMD and then to CRMM and death. BA acceleration was the residual from regressing BA on chronological age; positive values indicated a biologically older individual. Results: PhenoAge acceleration showed stronger associations than KDMAge acceleration. Per the 1-SD increase in PhenoAge acceleration; HRs (95% CIs) were observed at 1.18 (1.17\u20131.19) for baseline to first CRMD; 1.24 (1.22\u20131.26) for first CRMD to CRMM; 1.25 (1.22\u20131.27) for baseline to death; 1.13 (1.11\u20131.15) for first CRMD to death; and 1.09 (1.06\u20131.12) for CRMM to death. Biologically older individuals by PhenoAge acceleration showed greater reductions in CRMD-free and total life expectancy than those by KDMAge acceleration. Age, socioeconomic status, education, smoking status, alcohol consumption, physical activity, and diet-modified risks for specific transitions. Conclusions: BA acceleration, particularly PhenoAge acceleration, relates to higher CRMM progression risk and shorter life expectancy. Combining BA acceleration with sociodemographic or lifestyle factors improves risk identification for specific transitions. BA acceleration offers the potential to guide CRMM prevention across its entire progression.<\/jats:p>","DOI":"10.3390\/nu17111783","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T20:16:22Z","timestamp":1748204182000},"page":"1783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Biological Age Acceleration Associated with the Progression Trajectory of Cardio-Renal\u2013Metabolic Multimorbidity: A Prospective Cohort Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4717-7784","authenticated-orcid":false,"given":"Yixing","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Statistics, La Trobe University, Melbourne 3086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghua","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2135-046X","authenticated-orcid":false,"given":"Lixin","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health, 655 Huntington Ave, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-6940","authenticated-orcid":false,"given":"Xiuhua","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing 100069, China"},{"name":"National Institute for Data Science in Health and Medicine, Capital Medical University, Beijing 100069, China"},{"name":"School of Medical and Health Sciences, Edith Cowan University, Perth 6027, Australia"},{"name":"Beijing Key Laboratory of Environment and Aging, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1161\/CIR.0000000000001184","article-title":"Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association","volume":"148","author":"Ndumele","year":"2023","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s12933-024-02347-3","article-title":"Lifestyle factors and their relative contributions to longitudinal progression of cardio-renal-metabolic multimorbidity: A prospective cohort study","volume":"23","author":"Zhang","year":"2024","journal-title":"Cardiovasc. 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