Exosomes from APCs ameliorate human skin fibroblast senescence via p53/p21 signaling pathway

Exosomes have emerged as important resources in skin regenerative medicine. However, only a limited number of studies have demonstrated the anti-aging effects of progenitor cell–derived exosomes. In addition, the development of novel effective progenitor cell–based therapies is crucial for the treatment of skin aging. In this study, the viability and proliferation of human adipose-derived progenitor cells (APCs) from young (18–25 years) and old (60–67 years) donors were compared. Exosomes derived from young (yAPC-Exos) and old (oAPC-Exos) APCs were collected and characterized, and their effects on senescent human dermal fibroblasts (HDFs), as well as the underlying molecular mechanisms, were investigated. The proliferation capacity of aged APCs was significantly reduced. Both yAPC-Exos and oAPC-Exos promoted HUVEC migration and tube formation, as well as HDF migration. Exosome treatment decreased intracellular reactive oxygen species levels and alleviated aging-associated phenotypes in senescent HDFs. These effects occurred primarily through p21 and p53 downregulation and SIRT1 upregulation. Notably, yAPC-Exos exerted more pronounced anti-senescent effects than oAPC-Exos. Taken together, yAPC-Exos may represent an effective therapeutic strategy for aging-related skin pathologies and cosmetic applications.