Aging of Skeletal Muscle: From Molecular Mechanisms to Therapeutic Interventions

ABSTRACT Skeletal muscle aging is a major cause of frailty, metabolic dysfunction, and loss of independence in later life, yet it cannot be explained by muscle mass loss alone. Recent single‐cell, multi‐omics, and translational studies show that aged muscle is shaped by coordinated changes in myofibers, stem and stromal cells, immune and vascular compartments, neuromuscular control, and systemic metabolism. This review describes skeletal muscle aging as a gradual loss of tissue resilience rather than a simple decline in muscle mass. Impaired proteostasis, mitochondrial dysfunction, chronic inflammation, and cellular senescence are discussed as major, closely linked processes that contribute to defective regeneration, matrix remodeling, fibro‐adipogenic conversion and denervation, and are influenced by endocrine, metabolic, liver‐, adipose‐, gut‐, and brain‐derived signals. Current therapeutic evidence is reviewed with an emphasis on exercise and nutritional optimization as the clinical foundation, while mitochondrial, anabolic, senescence‐directed, and regenerative strategies are considered as emerging or investigational approaches. By bringing these findings together, this review highlights how studies of muscle aging can move beyond descriptive changes in mass and strength toward a clearer understanding of the biological processes that limit muscle function in later life.