Biological age-acceleration in relation to muscle mass, strength and function: findings from the Hertfordshire Cohort Study

INTRODUCTION: Sarcopenia, the accelerated loss of muscle mass, strength and function with age, is associated with adverse health outcomes. DNA methylation accumulates across life and methylation clocks (which provide a measure of biological age) could potentially be used to predict individuals at high sarcopenia risk. In this study, we examined biological age-acceleration measures in relation to sarcopenia components. METHODS: Overall, 331 participants from the UK community-dwelling Hertfordshire Cohort Study were analysed. At baseline (1998-2004), participants underwent health assessments and provided blood samples. At follow-up (2011-12), appendicular lean mass (ALM) index was ascertained using DXA; muscle strength by grip dynamometry; and gait speed over 8ft (2.44 m). DNA was extracted from peripheral blood leukocytes and DNA methylation at CpG sites was measured using the Infinium Human Methylation Beadchip array. Methylation clock measures were ascertained, and examined in relation to grip strength, gait speed and ALM index using linear regression, and in relation to a sarcopenia score (number of sarcopenia components) using Poisson regression. Baseline age, follow-up time, height and BMI were included as adjustments. RESULTS: At baseline, mean (SD) age was 65.1 (2.8) years. Among males, greater age-acceleration was related to lower grip strength; the standard deviation (SD) difference in grip strength per SD increase in age-acceleration was - 0.16 (-0.32, -0.01) for Principal Component (PC) PhenoAge and - 0.16 (-0.31, -0.01) for bAge. Associations regarding grip strength among females, and for gait speed and ALM index among both males and females were weak. The multiplicative increase in sarcopenia score per SD increase in age-acceleration among females was 1.23 (1.04, 1.45) for PCHorvath1, and 1.20 (1.02, 1.41) for PCHorvath2 (p = 0.02 for both associations). CONCLUSIONS: Greater age-acceleration was related to lower grip strength among males only, and associations regarding gait speed and ALM index were weak among both sexes. Greater baseline biological age-acceleration was related to a higher sarcopenia score among females. These findings require further investigation in larger cohorts.