Work

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

Year: 2026

Type: article

Abstract: 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.

Source: iScience

DOI: 10.1016/j.isci.2026.115234