Cross-sectional associations of epigenetic clocks with intrinsic capacity and functional ability in older adults with frailty and cognitive impairment: the COGFRAIL study

Abstract

Functional ability and intrinsic capacity (IC) have been proposed as determinants of healthy aging, but the extent to which these indicators are affected by biological aging remains unknown. We explored the association of biological age acceleration (BAA) with functional ability and IC in older adults with physical and cognitive impairments. This cross-sectional study used data from 163 individuals (84.0 ± 5.2 years [range 72–99], 61.8% women) of the COGFRAIL cohort. Functional ability on basic (BADL-Katz Index) and instrumental activities of daily living (IADL-Lawton Index) was assessed. IC was measured as a composite score (0–100, higher is better) including the locomotion, cognition, psychology, sensory, and vitality domains. BAA was assessed by Horvath’s, Hannum’s, PhenoAge, and GrimAge epigenetic clocks. In the fully adjusted model, higher BAA_PhenoAGe was associated to lower functional ability in BADLs (β = − 0.021, 95% confidence interval = − 0.038 to − 0.003, p = 0.022), with no significant results observed for the remaining clocks. No significant association was found between BAA and IC, but some associations were found with specific IC domains. Particularly, BAA_GrimAge was associated with lower locomotion scores (β = − 1.179, 2.286 to − 0.072, p = 0.037), while BAA_PhenoAge tended to be associated with lower scores in vitality (β = − 0.257, − 0.539 to 0.025, p = 0.073). Higher BAA_Phenoage was associated with lower functional ability in very old adults with frailty and cognitive impairment. Although no biological clock was associated with a composite IC score, some associations were found between second-generation epigenetic clocks and specific IC domains.