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.