Associations of Skin Biomechanical Properties With Biological Aging Clocks and Longitudinal Changes in Intrinsic Capacity in Adults Aged 20-93: The INSPIRE-T Project

Abstract

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.

Keywords: biomarkers; biomechanical phenomena; epigenesis; healthy aging; inflammation; intrinsic capacity; skin aging.

FIGURE 1

Correlations between skin elasticity/viscoelasticity parameters and age. (A–E) Scatterplots show how Cutometer R parameters varied by age. Blue points represent men, and red points represent women. R0, skin distensibility; R2, gross elasticity; R5, net elasticity; R6, viscoelastic ratio; R7, biological elasticity. (F) A correlation matrix representing Spearman's rank correlation coefficients between age and R parameters. All p values for the correlations were statistically significant (p < 0.05), except for the comparison between parameters R5 and R6 (p = 0.05).

FIGURE 2

Effect of skin elasticity (R2, R5, R7) and viscoelasticity (R6) parameters on baseline IC at ages 40, 65, and 80. The interaction plots illustrate how the effects of Cutometer R parameters on baseline IC scores varied by age, using 40, 65, and 80 years as examples. Results are presented for the whole population (A–D), women (E–H), and men (I–L). The slopes of R parameters were estimated by holding time = 0 and ages = 40, 65, and 80, respectively, using the linear mixed‐effect models in Table 2 (for the whole population) and Table 3 (for women and men). Overall, the association between baseline IC and R parameters differed between younger (age 40; in red) and older individuals (age 65 and 80; in blue and green), as indicated by the opposite slope directions in the plots. R2, gross elasticity; R5, net elasticity; R6, viscoelastic ratio; R7, biological elasticity.

FIGURE 3

Predicted IC over 3 years by different levels of R6 and ages. The interaction plots illustrate how the effect of the viscoelastic ratio R6 on the overtime IC change varied by ages, using age = 40, 65, and 80 years and standardized R6 values = −1, 0, and 1 as examples. The slopes of time (referring to the overtime IC change) were estimated using the linear mixed‐effect models in Table 2 (for the whole population) and Table 3 (for women and men). (A) IC tended to be improved over time in individuals aged 40 (positive slopes in the plots) and relatively stable or declining at ages 65 and 80. (B, C) Women aged 40 with increased R6 were associated with a higher IC initially and a greater improvement in IC over three years. On the contrary, in older people, especially men, an increased R6 was associated with a lower baseline IC and a faster IC decline.