Associations of proteomic age clocks with lifestyle risk factors, incident chronic diseases and mortality in two European cohorts

Assessment of biological aging using proteomic clocks may enhance risk prediction and elucidate the molecular links between aging and chronic diseases. Here, among 17,473 participants of the European Prospective Investigation into Cancer and Nutrition, we examined associations of plasma SomaScan-based proteomic clocks, including organ-specific clocks, with risk factors, 24 incident chronic diseases and all-cause mortality, over up to 28 years of follow-up. Replication was conducted in the Whitehall II study. We show that the global age gap, an age acceleration score combining proteomic clocks, was associated with smoking, alcohol consumption, physical inactivity and higher risk of mortality, cardiovascular diseases, dementia and cancers of the liver, upper aero-digestive tract, lung and kidney. Lung, kidney and stomach cancers were more strongly associated with related organ-specific age gaps. Predictive performance of proteomic clocks for mortality was comparable to that of classical lifestyle risk factors. In summary, proteomic clocks appear promising biomarkers of generalized age-related disease risk.