Plasma-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systems

Abstract Aging is a complex process manifesting at the molecular, cell, organ and organismal levels. It leads to functional decline, disease and ultimately death, but the relationship between these fundamental biomedical features remains elusive. By applying machine learning to plasma proteome data of over fifty thousand human subjects in the UK Biobank and other cohorts, we report organ-specific and conventional aging models trained on chronological age, mortality and longitudinal proteome data. We show how these tools predict organ/systems-specific disease through numerous phenotypes. We find that men are biologically older and age faster than women, that accelerated aging of organs leads to diseases in these organs, and that specific diets, lifestyles, professions and medications are associated with accelerated and decelerated aging of specific organs and systems. Altogether, our analyses reveal that age-related chronic diseases epitomize accelerated organ- and system-specific aging, modifiable through environmental factors, advocating for both universal whole-organism and personalized organ/system-specific anti-aging interventions.