Human plasma extracellular vesicles as an exercise mimetic to preserve skeletal muscle plasticity during disuse

The purpose of this study was to determine the extent to which extracellular vesicles (EVs) circulating in blood after exercise training act as an effective mimetic to maintain skeletal muscle mass during unloading and/or accelerate recovery after disuse. Ten healthy males (27.7 ± 7.1 y) were recruited for a 6-week progressive resistance and endurance training program. EVs were isolated from blood before (EVs) or immediately after training (ExerVs). EVs were intraperitoneally injected into male mice (4×; 3 × 10⁸ particles/injection) during 14 days of hindlimb unloading (HU), then the muscles were collected immediately or 7 days after HU. ExerVs did not maintain muscle mass, fiber size (fCSA), or protein synthesis but significantly reduced collagen I during HU. ExerV administration rapidly restored Type I fCSA and capillary quantity concomitant with reduced collagen during the reloading period. Overall, this study demonstrates that ExerVs may represent a novel strategy to preserve skeletal muscle health during disuse.