Heterogeneous aging across multiple organ systems and prediction of chronic disease and mortality

Abstract Biological aging of human organ systems reflects the interplay of age, chronic disease, lifestyle and genetic risk. Using longitudinal brain imaging and physiological phenotypes from the UK Biobank, we establish normative models of biological age for 3 brain and 7 body systems. We find that an organ’s biological age selectively influences the aging of other organ systems, revealing a multiorgan aging network. We report organ age profiles for 16 chronic diseases, where advanced biological aging extends from the organ of primary disease to multiple systems. Advanced body age associates with several lifestyle and environmental factors, leucocyte telomere lengths and mortality risk, and predicts survival time (AUC=0.77) and premature death (AUC=0.86). Our work reveals the multisystem nature of human aging in health and chronic disease. It may enable early identification of individuals at increased risk of aging-related morbidity and inform new strategies to potentially limit organ-specific aging in such individuals.