Mapping structural aging across human tissues reveals tissue-specific trajectories and coordinated deterioration

Vollständiger Abstract

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Abstract Organ structure, including the organization of cells, vasculature and extracellular matrix, underpins its function, yet how structure changes with age remains mostly unknown. Here we developed PathStAR, a framework that quantifies tissue structural aging from routine histopathology images, without being trained to predict chronological age. Applying PathStAR to 25,306 post-mortem biopsies from 40 tissues in 970 donors aged 21–70 years revealed that organ structural aging progresses via distinct, nonlinear temporal trajectories: vascular tissue structural aging accelerates early, uterus and vagina structural aging accelerates late (around menopause) and certain tissues including digestive and male reproductive organs show biphasic accelerations. We show that accelerations of structural aging are characterized across organs by increased inflammation alongside reduced energy production, repair and quality control. Cross-organ analysis reveals coordinated deterioration within individuals, including digestive and male reproductive tissues, linked by sex hormones. Together, our analysis provides a systematic map of structural aging across the human body.