Apigenin enhancing oxidative resistance and proteostasis to extend lifespan via PTEN-mediated AKT signalling pathway

Aging is a complicated process, featuring the progressive deterioration of physiological functions and a heightened susceptibility to diseases including neurodegenerative disorders, cardiovascular diseases, and cancer. Apigenin, a flavonoid existing in various plants, has attracted attention due to its potential role in anti-aging. In this investigation, the potential effect of apigenin on extending lifespan in Saccharomyces cerevisiae (yeast) and Drosophila melanogaster (flies) was explored. The results indicate that apigenin significantly extends both replicative and chronological life duration in yeast, as well as longevity in male and female flies. Apigenin treatment also improves resistance to oxidative stress in both organisms, as manifested by enhanced survival, decreased reactive oxygen species (ROS) levels and upregulation of antioxidant enzymes. Furthermore, apigenin activates crucial elements of the proteostasis network (PN), such as upregulation of proteostasis-related enzymes activity and genes expression. Network analysis revealed that apigenin affects aging conserved in the longevity-regulating pathway. Notably, Pten is a hub target in flies. Apigenin regulated DmPten at both mRNA and protein expression level while modulating downstream targets, including the phosphorylation of AKT and associated signalling pathways. In a high-sucrose diet (HSD) model, Apigenin treatment extended lifespan, reduced hemolymph glucose levels, enhanced Pten expression, suppressed AKT phosphorylation, and modulated the phosphorylation status of S6K and expression of DmFoxo. These results demonstrate that apigenin could serve as a longevity research object and potential therapeutic drug for promoting health and longevity through its antioxidant and proteostatic properties.