Exercise induces Skeletal Muscle Methylome and Transcriptome changes, regardless of Age and COPD

Abstract

Skeletal muscle atrophy and deconditioning contribute to functional limitation and disability in COPD. While transcriptome and DNA methylation changes accompany exercise in healthy muscle, their interaction with COPD status and ageing, and integrative analyses of methylome-transcriptome responses have not been explored. We performed gene expression and DNA methylation profiling in skeletal muscle of sedentary volunteers with COPD, age-matched older adults, and younger healthy individuals, before and during (1,4 and 8 weeks) supervised aerobic exercise training and after four weeks of detraining. Exercise induced transcriptomic and DNA methylation changes, but these responses were unaffected by COPD status or age. Subsequent analysis focusing on temporal exercise effects independent of disease or age revealed differential transcriptomic changes across time points, a subset of which significantly associated with DNA methylome alterations. Transient transcriptomic changes not linked to DNA methylation were enriched for inflammatory and oxidative stress pathways, whereas persistent methylation-associated adaptations were related to immunomodulation and tissue remodelling. Together, this study provides insight into molecular mechanisms contributing to skeletal muscle adaptation to aerobic exercise training in sedentary individuals.