Ergothioneine exhibits longevity-extension effect in Drosophila melanogaster via regulation of cholinergic neurotransmission, tyrosine metabolism, and fatty acid oxidation

Many studies have demonstrated the protective effect of ergothioneine (EGT), the unique sulfur-containing antioxidant in mushrooms, on several aging-related diseases. Nevertheless, to date, no single study has explored the potential role of EGT in the lifespan of animal models. We show here that EGT consistently extended fly life span in diverse genetic backgrounds and both sexes, as well as in a dose and gender-dependent manner. Additionally, EGT is shown to increases the climbing activity of flies, enhances AchE activity, and maintains GSH/GSSG ratios of aged flies. An increase in life span by EGT was gut microorganisms dependent. Altogether, we proposed potential mechanisms of lifespan extension in Drosophila by EGT through RNA-seq analysis: preservation of the normal status of the central nervous system via the coordination of cholinergic neurotransmission, tyrosine metabolism, and peroxisomal proteins, regulated autophagic activity by altering the lysosomal protein CTSD, and the preservation of normal mitochondrial function through the controlled substrate feeding into the TCA cycle