Extracellular Vesicles From Young Human Myogenic Progenitor Cells Rejuvenate Aged Cells

The physiological age-related decline in skeletal muscle mass, power, and function is challenging for humans. Skeletal muscle has been recently recognized as a secretory organ, with human myogenic progenitor cells (hMPCs) releasing extracellular vesicles (EVs). Here, we investigate the role of hMPC-derived EVs as mediators in skeletal muscle aging. This heterologous approach enables the analysis of age-related variations in EV burden and their impact on human muscle stem cell function. Therefore, we isolated EVs from hMPCs obtained from vastus lateralis muscle biopsies of young and elderly subjects. Then, we characterized EVs for specific marker, size, and concentration and analyzed their miRNA expression and proteomic profiles to delineate the bioactive cargo that influences recipient cell signaling. Next, we tested the ability of EVs to modulate on hMPCs. Specifically, we treated elderly hMPCs with young EVs and vice versa to analyze viability and differentiation. Our results demonstrate that EVs released by young hMPCs carry regenerative signals that mitigate the functional decline of aged muscle stem cells. Conversely, the EVs derived from elderly hMPCs compromise the regenerative capacity of their younger counterparts. Therefore, these results suggest that hMPCs release EVs and that their cargo is modulated by donor age. Moreover, the EVs significantly modulated hMPCs' viability and differentiation in cell culture.