PathStAR maps organ-specific aging timelines and coordinated tissue decline
PathStAR (Pathology-based Structural Aging Rate) quantifies tissue structural aging from routine H&E slides without training on chronological age, analyzing ~25,000 GTEx postmortem biopsies from 970 donors (21–70 years) across 40 tissues. It reveals distinct, nonlinear aging trajectories: vascular tissues accelerate early, uterus and vagina accelerate around menopause, and several digestive and male reproductive organs show biphasic aging. Accelerations accompany increased inflammation and reduced energy production, repair, and quality control; cross-tissue analysis shows coordinated aging within individuals, including sex-specific patterns like uterus–vagina coupling, and germline variant burden associating with faster aging in certain tissues. PathStAR provides a new, quantitative dimension of aging that complements molecular clocks and is available as open-source software with GTEx data.