Cellular Senescence in Skeletal Muscle: Myogenic and Non-Myogenic Cell Populations, Mechanisms, and Therapeutic Opportunities

Skeletal muscle plays a central role in systemic metabolism, physical function, and overall health. Aging and disease diminish the ability of myogenic and non-myogenic skeletal muscle cells to coordinate adaptation and repair, but the mechanisms underlying this decline are not fully understood. Growing evidence implicates cellular senescence, a stress response marked by irreversible cell-cycle arrest and pro-inflammatory signaling, as a key contributor to muscle pathology. In this review, we synthesize current insights into the molecular mechanisms that govern cellular senescence in skeletal muscle, its effects on myogenic and non-myogenic cell populations, and recent technologies that have clarified key aspects of senescence biology. We further explore emerging therapeutic strategies aimed at targeting senescent cells and discuss key knowledge gaps that must be addressed to advance our understanding of senescent myogenic and non-myogenic cells in skeletal muscle.