Patterns of Organ‐Specific Proteomic Aging in Relation to Lifestyle, Diseases, and Mortality

Aging occurs in a heterogeneous manner across different organs, leading to varying risks of chronic diseases and mortality. Biological age offers a more comprehensive reflection of the aging process and is a stronger predictor of disease risk and lifespan. Recent advances in plasma proteomics have enabled the development of organ-specific aging clocks, revealing the distinct aging trajectories and their clinical implications. We used protein-based aging estimators for 11 organs, applying them to plasma data using elastic net regularization. A comprehensive analysis of associations was conducted with 86 lifestyle and environmental factors, 657 diseases through phenome-wide association studies (PheWAS), and all-cause mortality. Our findings revealed that organ aging is influenced by lifestyle factors and baseline health conditions, highlighting its dynamic and modifiable nature. Additionally, accelerated organ aging is associated with a higher incidence of disease and an increased risk of all-cause mortality, particularly when it occurs earlier in life. Our large-scale lifestyle atlas and PheWAS offer actionable insights into the modifiable drivers of organ aging, advancing strategies for disease prevention and longevity.