In this study, Sahu and colleagues evaluated the contribution of circulating EVs to the beneficial effect of young serum on aged muscle stem cells and the skeletal muscle regenerative cascade. The UPMC researchers showed that young serum restores a youthful bioenergetic and myogenic profile to aged muscle cell progeny from muscle stem cells. This effect depends on the presence of circulating EVs. Moreover, whereas youthful EV cargoes preserve mitochondrial structure and function in target muscle cells, aged EV cargoes propagate mitochondrial dysfunction.
Sahu and colleagues next evaluated whether circulating EVs contribute to the previously reported beneficial effects of young serum on skeletal muscle regeneration in mice. For this, aged mice received serial tail-vein injections of young serum as is or depleted of EVs. By 11 days after injury, blood exchange significantly enhanced skeletal muscle regeneration and functional recovery, as determined by myofiber cross-sectional area and contractile testing, respectively. However, the beneficial effect of young serum on the regenerative potential of muscle was lost in the absence of circulating EVs. This shows that the beneficial effect of young serum on aged muscle regeneration and function is dependent, at least in part, on circulating EVs.