Associations of Skin Biomechanical Properties With Biological Aging Clocks and Longitudinal Changes in Intrinsic Capacity in Adults Aged 20–93: The <scp>INSPIRE</scp>‐T Project

Evidence connecting skin aging to functional decline and systemic aging biomarkers is lacking. This study investigated how skin-aging biomechanics were associated with changes in intrinsic capacity (IC), a marker of healthy aging. We also explored their links with biological aging clocks (epigenetic and inflammatory clocks) and potential moderating effects on the skin-IC relationship. Baseline skin elasticity and viscoelasticity were measured in 441 INSPIRE-T participants aged 20 to 93 (59.9% women) using Cutometer parameters. IC was evaluated over 3 years as a five-domain score covering cognition, locomotion, psychology, vitality, and sensory (a higher score indicated better). Biological aging was measured at baseline using six epigenetic clocks (Horvath pan-tissue, Horvath skin & blood, Hannum, PhenoAge, GrimAge, and DunedinPACE) and inflammatory clock (iAge). Poor skin elasticity and viscoelasticity in older adults were associated with lower baseline IC after controlling for demographic, medical, and lifestyle factors. Longitudinally, older men with a higher viscoelastic ratio (R6) experienced a faster decline in IC (a standardized coefficient [95% CI] ranged from -0.37 [-0.72, -0.03] at age 62 to -1.32 [-1.91, -0.73] at age 93). Accelerated iAge was associated with reduced skin elasticity (R2, R5, R7). Moreover, the association between parameters related to elastic recovery (R5, R7) and baseline IC became more pronounced as accelerated iAge increased. This is the first study demonstrating the association between skin-aging biomechanics and IC. Poor skin elasticity was associated with higher systemic inflammation. Therefore, skin biomechanical properties may reflect overall functional aging, with inflammation serving as a common underlying factor.