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Here, using plasma proteomics and machine learning, we developed organismal and ten organ-specific aging clocks in the UK Biobank (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200943,616) and validated their high accuracy in cohorts from China (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093,977) and the USA (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009800; cross-cohort\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.98 and 0.93). Accelerated organ aging predicted disease onset, progression and mortality beyond clinical and genetic risk factors, with brain aging being most strongly linked to mortality. Organ aging reflected both genetic and environmental determinants: brain aging was associated with lifestyle, the\n                    <jats:italic>GABBR1<\/jats:italic>\n                    and\n                    <jats:italic>ECM1<\/jats:italic>\n                    genes, and brain structure. Distinct organ-specific pathogenic pathways were identified, with the brain and artery clocks linking synaptic loss, vascular dysfunction and glial activation to cognitive decline and dementia. The brain aging clock further stratified Alzheimer\u2019s disease risk across\n                    <jats:italic>APOE<\/jats:italic>\n                    haplotypes, and a super-youthful brain appears to confer resilience to\n                    <jats:italic>APOE4<\/jats:italic>\n                    . Together, proteomic organ aging clocks provide a biologically interpretable framework for tracking aging and disease risk across diverse populations.\n                  <\/jats:p>","DOI":"10.1038\/s43587-025-01016-8","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:02:23Z","timestamp":1764151343000},"page":"162-180","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Organ-specific proteomic aging clocks predict disease and longevity across diverse 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