Quercetin Prevents Intestinal Stem Cell Aging via Scavenging ROS and Inhibiting Insulin Signaling in Drosophila

Adult stem cells, a class of cells that possess self-renewal and differentiation capabilities, modulate tissue regeneration, repair, and homeostasis maintenance. These cells undergo functional degeneration during aging, resulting in decreased tissue regeneration ability and increased disease incidence. Thus, it is essential to provide effective therapeutic solutions to preventing the aging-related functional decline of stem cells. Quercetin (Que) is a popular natural polyphenolic flavonoid found in various plant species. It exhibits many beneficial effects against aging and aging-related diseases; however, its efficacy against adult stem cell aging remains largely unclear.Drosophilapossesses a mammalian-like intestinal system with a well-studied intestinal stem cell (ISC) lineage, making it an attractive model for adult stem cell research. Here, we show that Que supplementation could effectively prevent the hyperproliferation of ISCs, maintain intestinal homeostasis, and prolong the lifespan in agedDrosophila. In addition, we found that Que could accelerate recovery of the damaged gut and improve the tolerance ofDrosophilato stressful stimuli. Furthermore, results demonstrated that Que prevents the age-associated functional decline of ISCs via scavenging reactive oxygen species (ROS) and inhibiting the insulin signaling pathway. Overall, our findings suggest that Que plays a significant role in delaying adult stem cell aging.Keywords:intestinal stem cell;aging;quercetin;insulin signaling;ROS;Drosophila