Adipose-derived stem cell exosomes attenuated fibroblast senescence by regulating endoplasmic reticulum stress...

Adipose-derived stem cells are widely used in aging field because of their extensive sources, low immunogenicity and strong secretory function. In particular, the exosomes of adipose-derived stem cells are rich in small molecules of RNA and protein. Studies have shown that exosomes also play a role in regulation of ER stress. Therefore, we hypothesized that exosomes of adipose-derived stem cells could regulate ER stress and delay fibroblasts senescence. In this study, we use H₂O₂ to promote cellular senescence and treat with adipose-derived stem cell exosomes. The function of cell proliferation and apoptosis were compared, and the levels of validating factor and collagen were detected. Then we explored the mechanism of action of exosomes derived from adipose-derived stem cells. We found adipose-derived stem cell exosomes could inhibit fibroblast senescence, including promoting cell proliferation, inhibiting apoptosis and regulating collagen secretion, by regulating ER stress through SIRT1. To further validate the relevance of this mechanism at the population level, public human skin transcriptomic data were analyzed, revealing coordinated downregulation of SIRT1 expression and unfolded protein response (UPR) signaling during physiological skin aging, with a strong positive correlation between SIRT1 expression and UPR pathway activity. This study suggests that adipose-derived stem cell exosomes attenuate stress-induced senescence-like changes in fibroblasts, highlighting their potential relevance in the modulation of cellular aging.