Proteomic aging clock predicts mortality and risk of common age-related diseases in diverse populations

Abstract Circulating plasma proteins play key roles in human health and could be used to measure biological aging to predict risk of mortality, disease, and multimorbidity beyond chronological age. We developed a proteomic age clock using 1,459 plasma proteins (Olink Explore) in two prospective biobanks in the UK (n=45,117) and China (n=2,026) and explored its utility to predict incident risk of 26 major age-related diseases and all-cause mortality. We identified 226 proteins that accurately predicted chronological age (Pearson r=0.92). Individuals in the top versus bottom deciles of accelerated proteomic aging differed by approximately 10 years of biological aging. In the UK population, accelerated proteomic aging was associated with 25 aging phenotypes (e.g., telomere(definition) length, IGF-1, creatinine, cystatin C, hand grip strength, cognitive function, frailty index), 18 chronic diseases (e.g., diseases of the heart, liver, kidneys, lungs; diabetes; neurodegeneration; cancers), multimorbidity, and all-cause mortality. In the smaller Chinese population, accelerated proteomic aging was associated with ischemic heart disease, stroke, and all-cause mortality. Our results demonstrate that plasma proteins are a reliable instrument for prediction of multiple common diseases in diverse populations and can be used as a robust biochemical aging signature to improve early detection and management of common diseases.