Large-scale Chemical Screen Identifies a Geroprotective Role of Gallic Acid in Premature Aging [ATAC-seq]

Gallic acid (GA) is a natural phenolic compound with antioxidant, anti-inflammatory, and antineoplastic properties. Previous studies also revealed that GA supplementation inhibit the decline of rat embryonic and rejuvenate the immune function in D-gal-induced aging accelerated mice. However, the role of GA in regulating senescence of human premature aging stem cells is unknown. We have demonstrated that GA showed beneficial effects in alleviating human mesenchymal stem cell (hMSC) senescence: (1) GA alleviated senescence by promoting stem cell self-renewal ability and down-regulating the expression of aging markers, including P16 and P21, in Werner syndrome (WS) hMSCs; (2) High levels of reactive oxygen species in total cell as well as mitochondria were both rescued by GA treatment; (3) GA also maintained epigenetic features, enhanced cell stemness, and improved mitochondrial homeostasis in WS hMSCs. Our data provide substantial evidence supporting that GA is a promising candidate agent to Overall design: ATAC sequencing in Werner syndrome (WS) hMSCs, DMSO-treated cells, GA (gallic acid)-treated cells.