Phenome-wide associations of human aging uncover sex-specific dynamics

Aging varies significantly among individuals of the same chronological age, indicating that biological age (BA), estimated from molecular and physiological biomarkers, may better reflect aging. Prior research has often ignored sex-specific differences in aging patterns and mainly focused on aging biomarkers from a single data modality. Here we analyze a deeply phenotyped longitudinal cohort (10K project, Israel) of 10,000 healthy individuals aged 40–70 years that includes clinical, physiological, behavioral, environmental and multiomic parameters. Follow-up visits are scheduled every 2 years for a total of 25 years. We devised machine learning models of chronological age and computed biological aging scores that represented diverse physiological systems, revealing different aging patterns among sexes. Higher BA scores were associated with a higher prevalence of age-related medical conditions, highlighting the clinical relevance of these scores. Our analysis revealed system-specific aging dynamics and the potential of deeply phenotyped cohorts to accelerate improvements in our understanding of chronic diseases. Our findings present a more holistic view of the aging process, and lay the foundation for personalized medical prevention strategies.