PhenoAge acceleration, serum tryptophan, and frailty in socially engaged actively aging elderly men

Biological aging varies substantially among older adults and may shape vulnerability to frailty beyond chronological age. We conducted a cross-sectional study of 928 socially engaged elderly men to examine the associations among phenotypic age (PhenoAge) acceleration, frailty-related traits, and circulating metabolites. PhenoAge acceleration, calculated from routine clinical biomarkers, was consistently associated with greater frailty severity, particularly among the old-old and those with lower physical activity. Targeted metabolomic profiling identified serum tryptophan as inversely associated with both PhenoAge acceleration and frailty-related phenotypes. Mediation analyses suggested that tryptophan statistically accounted for part of the association between biological aging and frailty. These patterns were further supported by age-matched sensitivity analyses and an independent external cohort. Together, our findings highlight the close linkage between biological aging, metabolic profiles, and frailty-related traits in actively aging populations and support the potential utility of integrating routine aging metrics with metabolic indicators to inform future longitudinal studies of healthy aging.