Epigenetics of sarcopenia: Insights into mechanisms and interventions for healthy muscle aging

Aging frequently correlates with the progressive decline in skeletal muscle mass and function, a condition termed sarcopenia. Epigenetic modifications, including DNA methylation, histone alterations, and microRNA regulation, critically influence gene expression changes throughout aging. This review elucidates molecular mechanisms underlying epigenetic alterations in aging skeletal muscle and their functional consequences. We elucidate how shifts in DNA methylation, histone modifications, and microRNA profiles contribute to muscle atrophy and dysfunction. Furthermore, we examine emerging therapeutic strategies targeting epigenetic pathways to mitigate age-related muscle deterioration. A deeper understanding of these epigenetic processes could facilitate the development of interventions to promote healthier aging and improve muscle function in older adults. A comprehensive understanding of these processes will guide therapeutic strategies aimed at improving elderly muscle health Keyeords Skeletal muscle aging; Epigenetics; DNA methylation; Histone modifications; Non-coding RNAs • Epigenetic remodeling reprograms aging muscle and promotes sarcopenia. • DNA methylation drift and DMRs disrupt NMJ, metabolism, and proteostasis(definition). • Histone marks and HDAC4 connect denervation to atrogene activation and fibrosis. • ncRNA networks shape MuSC function, mitochondrial QC, and inflammatory signaling. • Muscle DNAm clocks quantify muscle aging and track intervention response.