Imaging-derived biological age across multiple organs links to mortality and aging-related health outcomes

Abstract Aging is a complex, multifactorial process, influencing disease risk and overall health. While chronological age (CA) is widely used in clinical practice, it fails to capture individual aging trajectories. Current approaches to estimate biological age (BA) often focus on single organs or predefined clinical biomarkers, limiting comprehensive assessment. We introduce a novel, purely imaging-driven deep learning framework for organ-specific BA estimation across seven organ systems. Our uncertainty-aware ResNet-based models autonomously learned aging-related features from imaging data in 70,000 UK Biobank participants, eliminating manual feature selection biases. Training on a healthy cohort, where CA approximates BA, allows learning normative aging patterns. When applied to a broader cohort, deviations from typical aging indicate older or younger BA. Our findings demonstrate the feasibility of BA estimation, even in organs with subtle aging features. While aging is largely heterogeneous across organs, we also identified correlations in aging patterns. We further showed that accelerated aging is prognostic of mortality and health outcomes, offering insights for personalized assessments.