Extracellular Vesicles from Young Plasma Produce Benefits in Old Mice
The evidence for transfusion of young plasma to produce benefits in old animals and human patients is mixed. Despite compelling demonstrations for the dilution of blood to produce benefits in older individuals, there remain many research groups who consider that the primary goal should be the identification of factors within young blood that can produce improvements to health. Inconveniently for those who argue for the primacy of dilution in producing the benefits of plasma transfusion, there are studies such as this one in which factors derived from young plasma do in fact improve health significantly in old mice.
Recent investigations into heterochronic parabiosis have unveiled robust rejuvenating effects of young blood on aged tissues. However, the specific rejuvenating mechanisms remain incompletely elucidated. Here we demonstrate that small extracellular vesicles (sEVs) from the plasma of young mice counteract pre-existing aging at molecular, mitochondrial, cellular and physiological levels. Intravenous injection of young sEVs into aged mice extends their lifespan, mitigates senescent phenotypes, and ameliorates age-associated functional declines in multiple tissues.
Quantitative proteomic analyses identified substantial alterations in the proteomes of aged tissues after young sEV treatment, and these changes are closely associated with metabolic processes. Mechanistic investigations reveal that young sEVs stimulate PGC-1α expression in vitro and in vivo through their microRNA cargoes, thereby improving mitochondrial functions and mitigating mitochondrial deficits in aged tissues. Overall, this study demonstrates that young sEVs reverse degenerative changes and age-related dysfunction, at least in part, by stimulating PGC-1α expression and enhancing mitochondrial energy metabolism.