Exercise-derived exosomes: molecular mediators of systemic health and disease therapy

Exosomes serve as pivotal nanoscale messengers in intercellular communication by transporting bioactive molecules such as miRNAs, proteins, and lipids that regulate physiological and pathological processes. Emerging evidence highlights exercise as a potent modulator of exosome biogenesis, dynamically altering their release kinetics, molecular cargo, and bioactivity across tissues. Exercise-derived exosomes disseminate systemic adaptations by delivering regulatory signals to noncontractile organs, thereby coordinating multitissue responses that underlie the protective and reparative benefits of physical activity. This review synthesizes current knowledge on the dynamic effects of acute and chronic exercise on exosome profiles and their therapeutic potential in treating neurological, cardiovascular, metabolic, and musculoskeletal disorders. This review further discusses how exosome engineering and precision medicine could harness exosomes as "exercise mimetics," offering cell-free therapeutics for mobility-limited populations. By integrating exercise physiology with translational medicine, this work pioneers a new therapeutic paradigm where exosome-based molecular therapies replicate exercise's multisystem benefits.