Epigenetics as Biomarkers of Cumulative Physical Performance in Community-Dwelling Adults: A Cross-Sectional Feasibility Study.

With global life expectancy steadily rising, promoting healthy aging is becoming a critical objective of public health. Physical function tends to decline gradually, often beginning in midlife, when subtle changes start to occur and accumulate undetected until later years. This study examines the feasibility of using DNA methylation-based epigenetic clocks as biomarkers for cumulative physical performance in 24 community-dwelling adults aged 39 years and older. Our findings reveal that several epigenetic age estimators, particularly DNAmAgeHannum, are significantly associated with a novel composite score criterion derived from standardized motor function assessments (DNAmAge: ρ = -0.48, <i>p</i> < 0.026; DNAmPhenoAge: ρ = -0.48, <i>p</i> < 0.026) with DNAmAgeHannum (ρ = -0.59, <i>p</i> < 0.005). These findings support the potential of using epigenetic aging markers to detect early physiological decline, even in relatively healthy, midlife populations, offering a promising tool for the early identification of age-related functional deterioration.