Phlorizin Prolongs the Lifespan of Caenorhabditis elegans by insulin/SIR-2.1 Regulation

Abstract

Abstract Phlorizin, a natural compound, was studied using C. elegans to explore its potential mechanism for extending lifespan. Results showed that phlorizin mitigated the harmful effects of high temperatures and hydrogen peroxide, reduced oxidative stress, increased antioxidant enzyme activity, and reduced MDA levels. Through network pharmacological analysis, it was determined that the AKT1, INSR and SOD2 signaling pathway plays a key role in the anti-aging effects of phlorizin. Experiments with mutants and transgenic C. elegans showed that phlorizin lifespan extension and antioxidant effects are mainly mediated by insulin and SIR-2.1 pathways that regulate DAF-16 and SKN-1 nuclear translocation and its downstream targets SOD-3 and HSP-16.2. These findings were supported by molecular docking experiments. Overall, this study provides insight into the potential use of phlorizin as an anti-aging agent and highlights the importance of the DAF-16/SOD-3 signaling pathway in mediating its action.