Sex-dependent geroprotective effects of malvidin in Drosophila melanogaster

Malvidin-3-galactoside (M3G), an anthocyanin derived from  blueberries (Vaccinium myrtillus L.), is recognized for its antioxidant and anti-inflammatory properties. In this study, Drosophila melanogaster was treated with M3G at concentrations of 1, 10, and 100 µM, while control groups received an identical diet without M3G supplementation. Treatment with M3G extended the lifespan of male flies by as much as 5% (p < 0.05). However, in females, certain concentrations of M3G resulted in reduced lifespan and diminished stress resistance, highlighting sex-specific responses. M3G enhanced male stress resistance, particularly against oxidative stress (induced by paraquat), heat shock (35 °C), and gamma radiation (300 Gy), increasing their median survival by 13% (p < 0.01), 10% (p < 0.05), and 12% (p < 0.05), respectively. Furthermore, M3G exhibited antioxidant effects by lowering levels of reactive oxygen species (ROS) and preventing lipid peroxidation in vitro, with no observed cytotoxicity. Gene expression analysis revealed marked changes in genes related to oxidative stress response (sod1, keap1, nrf2), lipid metabolism (bmm, Lip3), and hypoxia (hif1), with more pronounced effects in males. These findings suggest that M3G holds promise as a geroprotective and antioxidant agent with sex-specific impacts on lifespan and stress tolerance.