Abstract
Organ-specific aging clocks hold great potential in reflecting organ health. In vivo imaging is inherently organ-specific and delineates structural and functional characteristics more objectively. However, there is no systematic evaluation of imaging-based aging clocks. We utilized 1777 imaging-derived phenotypes (IDPs) from 11,000 healthy participants and assessed the organ-specific biological age of seven organs. The organ-specific age gap was primarily associated with incident diseases and mortality related to corresponding organs. The top-contributing IDPs to organ-specific biological age emerged as biomarkers for incident disease predictions, achieving an area under the curve (AUC) greater than 0.8 for dementia (AUC = 0.82). Subsequent proteomic analysis revealed 966 shared and 507 organ-specific molecular signatures for the aging of different organs. Finally, we identified key modifiable factors and 14 drug targets for organ-specific aging. The imaging-based aging clocks demonstrate organ-specificity at both macro and micro scales, which could promote personalized intervention and treatment of organ aging.