Effects of exercise‑derived extracellular vesicles: Epigenetic regulatory mechanisms and protective roles (Review)

Exercise exerts broad and sustained effects on metabolic homeostasis and overall physiology. However, the circulating mediators connecting localized exercise responses to coordinated systemic adaptation remain poorly defined, particularly those involved in inter‑organ communication and long‑term metabolic remodeling. Extracellular vesicles (EVs) have gained significant attention as key mediators in this signaling process, owing to their ability to transport proteins, metabolites, and RNAs between donor and recipient cells. Exercise dynamically modulates EV release, abundance, and cargo composition, suggesting that EVs may act as key mediators of exercise‑induced multisystem adaptation. Notably, exercise may alter the epigenetically active cargo of EVs, regulating epigenetic responses in target organs and ultimately shaping systemic metabolic homeostasis. Given the potential importance of these mechanisms in the long‑term systemic effects of exercise, a comprehensive review of the current evidence is essential. In the present review EV‑mediated epigenetic signaling in exercise is investigated, focusing on how exercise reshapes EV biogenesis and cargo composition, how EV‑associated epigenetic factors regulate recipient‑cell function, and how these processes may contribute to sustained metabolic adaptation. This perspective aims to clarify the mechanistic basis of exercise benefits and to highlight EVs as potential targets for precision diagnostics and therapeutic strategies.