Biological Ageing Acceleration and Functional Capacities Across the Lifespan in the INSPIRE‐T Cohort

BACKGROUND: Biological clocks are promising tools for the evaluation of biological age deviations (i.e., positive/negative acceleration). Here, we explored the associations of biological age acceleration (BAA) assessed by Horvath's, Hannum's, PhenoAge, and GrimAge epigenetic clocks, as well as the iAge inflammation-based clock, with functional capacities across adulthood and tested if chronological age and sex moderate these associations. METHODS: Cross-sectional analysis was conducted with baseline (2019-2021) data from 1014 participants (age range 20-104 years old, 62.82% female) drawn from the Inspire Translational Human cohort, a community-based program in South-West France. Physical capacity endpoints included the five-time sit-to-stand test (5-STS), the Short Physical Performance Battery (SPPB), the 30-s chair stand test (30-s CST), maximum oxygen uptake (VO2max) and isokinetic muscle strength (IMS). Multivariate linear regression was used to explore the associations of BAA (with and without interacting with chronological age or sex) with functional capacity endpoints. RESULTS: A total of 1014 individuals with available data on BAA and functional capacities were included (median age 64, IQR = 49-78, 62.82% female). GrimAge was the clock that more strongly correlated with functional capacities. Higher GrimAge BAA was associated with worse 5-STS (β = 0.25, 95% CI = 0.07, 0.43; p = 0.002), SPPB (β = -0.10, 95% CI = -0.18, -0.02; p = 0.019) and VO2max (β = -1.17, 95% CI = -1.81, -0.52; p < 0.001) across the whole adulthood. When the moderation effect of age was explored, BAA acceleration assessed by GrimAge was associated with worse 30-s CST in early adulthood. Increased iAge BAA was associated with poor SPPB and 5-STS at older age, whereas Horvath's BAA correlated with a decline in 30-s CST. CONCLUSIONS: Among four DNA methylation epigenetic clocks and one inflammatory clock, our study shows that GrimAge is the biological ageing clock that best associates with different measures of functional capacity, from young to older adulthood.