Mechanisms of Exercise‐Induced Skeletal Muscle Extracellular Vesicle Secretion and Their Physiological Functions: A Review

The secretion of extracellular vesicles (EVs), particularly exosomes, from skeletal muscle cells is a dynamic and highly regulated process predominantly controlled by intracellular signaling pathways activated during exercise. Physical activity stimulates metabolic and mechanical signals that activate AMP-activated protein kinase (AMPK) and calcium ion (Ca2+) signaling cascades, promoting multivesicular body formation and trafficking, thereby enhancing EV biogenesis and release. The quantity and characteristics of EV secretion vary according to exercise intensity, duration, and modality, with distinct secretion patterns observed between endurance and resistance training. Exercise-induced oxidative stress and mechanical stretch further modulate EV release by altering intracellular redox states and cytoskeletal dynamics. Pharmacological inhibition of EV secretion has revealed their critical role in exercise-induced vascular and systemic adaptations. Moreover, aging and metabolic diseases impair EV biogenesis and secretion, while resistance training can partially restore EV secretion functions in elderly individuals. Collectively, skeletal muscle EV secretion represents a finely tuned outcome of exercise-induced intracellular signaling and mechanical stimuli, serving as a crucial mechanism for systemic communication and adaptation. This review aims to comprehensively summarize the current understanding of the molecular mechanisms underlying exercise-induced skeletal muscle EV secretion and elucidate their physiological roles, highlighting potential therapeutic implications and future research directions in muscle biology and exercise physiology.