Skeletal Muscle-Derived Extracellular Vesicles in Interorgan Communication During Aging.

Skeletal muscle is increasingly recognized as a secretory organ that communicates with distant tissues through the release of bioactive factors, including extracellular vesicles (EVs). During aging, muscle-derived EVs have emerged as important mediators of interorgan communication, influencing tissue homeostasis, regeneration, metabolism, and disease progression. Recent studies demonstrate that skeletal muscle EVs carry diverse cargos such as proteins, lipids, metabolites, and regulatory RNAs that can modulate the function of recipient cells in multiple organs. In particular, aging-associated alterations in EV biogenesis, cargo composition, and secretion may contribute to chronic inflammation, stem cell dysfunction, metabolic decline, and age-related pathologies. In this review, we summarize current advances in skeletal muscle-derived EV biology and their roles in interorgan communication during aging. We discuss mechanisms regulating EV formation and cargo loading, their impact on stem cell function and tissue regeneration, and their involvement in aging-related diseases. We also highlight the translational potential of muscle EVs as biomarkers and therapeutic targets. Together, these findings identify muscle-derived EVs as key regulators of systemic aging and interorgan signaling.