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Here, we seek to understand complex interactions among metabolism, aging, and systems\u2010wide phenotypes across the lifespan. Among 2469 adults (mean age 74.7\u2009years; 38% Black) in the Health, Aging and Body Composition study we identified metabolic cross\u2010sectionally correlates across 20 multi\u2010dimensional aging\u2010related phenotypes spanning seven domains. We used LASSO\u2010PCA and bioinformatic techniques to summarize metabolome\u2010phenome relationships and derive metabolic scores, which were subsequently linked to healthy aging, mortality, and incident outcomes (cardiovascular disease, disability, dementia, and cancer) over 9\u2009years. To clarify the relationship of metabolism in early adulthood to aging, we tested association of these metabolic scores with aging phenotypes\/outcomes in 2320 participants (mean age 32.1, 44% Black) of the Coronary Artery Risk Development in Young Adults (CARDIA) study. We observed significant overlap in metabolic correlates across the seven aging domains, specifying pathways of mitochondrial\/cellular energetics, host\u2010commensal metabolism, inflammation, and oxidative stress. Across four metabolic scores (body composition, mental\u2010physical performance, muscle strength, and physical activity), we found strong associations with healthy aging and incident outcomes, robust to adjustment for risk factors. Metabolic scores for participants four decades younger in CARDIA were related to incident cardiovascular, metabolic, and neurocognitive performance, as well as long\u2010term cardiovascular disease and mortality over three decades. Conserved metabolic states are strongly related to domain\u2010specific aging and outcomes over the life\u2010course relevant to energetics, host\u2010commensal interactions, and mechanisms of innate immunity.<\/jats:p>","DOI":"10.1111\/acel.14090","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:44:10Z","timestamp":1706575450000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Implications of metabolism on multi\u2010systems healthy aging across the lifespan"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2125-1242","authenticated-orcid":false,"given":"Shanshan","family":"Yao","sequence":"first","affiliation":[{"name":"University of Pittsburg  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Colangelo","sequence":"additional","affiliation":[{"name":"Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3342-6158","authenticated-orcid":false,"given":"Andrew S.","family":"Perry","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan M.","family":"Marron","sequence":"additional","affiliation":[{"name":"University of Pittsburg  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Yaffe","sequence":"additional","affiliation":[{"name":"University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanaz","family":"Sedaghat","sequence":"additional","affiliation":[{"name":"University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao A. 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