A Scorpion Venom-Derived Peptide M6 Endowed with Anti-Aging Ability via Enhanced Antioxidant Activity in Cells, <i>Caenorhabditis elegans</i> and Mouse Models.

With an aging population and the prevalence of oxidative damage-related ailments, the quest for effective antioxidant and anti-aging agents has emerged as a focal point of biomedical research. Within this domain, peptides have garnered considerable attention for their potential activities. Hence, the current study investigates the antioxidant and anti-aging properties of a scorpion venom-derived peptide M6. We demonstrated that this peptide decreases H₂O₂-dependent apoptosis by binding to the TNFR1 receptor, which activates the NF-κB signaling pathway, thereby enhancing the capacity of cells to mitigate oxidative damage induced by H₂O₂ treatment. Moreover, M6 prolonged the lifespan of <i>C. elegans</i> and enhanced their thermal stress resistance. Further studies demonstrated that M6 inhibits the IIS/PI3K/AKT signaling pathway and activates <i>daf-16</i> and <i>skn-1</i> (homologous to Nrf-2), thereby enhancing the antioxidant capacity of nematodes and alleviating oxidative damage. Furthermore, M6 also alleviated D-galactose-induced oxidative damage in mice by enhancing the activity of catalase and superoxide dismutase. We also showed that M6 treatment protects liver and kidney tissues from oxidative damage induced by D-galactose. These results highlight the beneficial antioxidant and anti-aging properties of the peptide M6, which appear to be a promising lead for addressing related diseases and mitigating the effects of aging.