Vitexin and isovitexin delayed ageing and enhanced stress-resistance through the activation of the SKN-1/Nrf2 signaling pathway

Vitexin and isovitexin, as potential SKN-1/Nrf2 (SKN-1 is a homologous protein of mammalian Nrf2) activators, extended lifespan and promoted healthspan in Caenorhabditis elegans. This study aims to elucidate the role of SKN-1/Nrf2 in vitexin and isovitexin-induced anti-aging and stress-resistance. Vitexin and isovitexin upregulated antioxidant gene and protein expressions, reduced ROS accumulation, and increased SKN-1 accumulation in the nucleus. They prolonged lifespan and clear ROS during stressful conditions in a skn-1-dependent manner. skn-1 was also found to be necessary for these compounds-induced longevity under normal conditions. They were also witnessed to retard cellular senescence and scavenge ROS in senescent cells by directly binding to the pocket of Keap1 to promote the dissociation and activation of Nrf2. This study showed that SKN-1/Nrf2 signaling was vital to delaying ageing and enhancing anti-stress capacity with vitexin and isovitexin. The findings provide new insights into apigenin C-glycosides activating the SKN-1/Nrf2 pathway and demonstrate their potential as candidates for innovative strategies in chemoprophylaxis against ageing and oxidative-related diseases.