Glutathione levels influence chronological life span of Saccharomyces cerevisiae in a glucose-dependent manner

Diet plays a key role in determining the longevity of the organisms since it has been demonstrated that glucose restriction increases life span whereas a high-glucose diet decreases it. However, the molecular basis of how diet leads to the aging process is currently unknown. We propose that the quantity of glucose that fuels respiration influences reactive oxygen species generation and glutathione levels, and both chemical species impact in the aging process. Herein, we provide evidence that mutation of the gene GSH1 in Saccharomyces cerevisiae diminishes glutathione levels. Moreover, glutathione levels were higher with 0.5% than in 10% glucose in the gsh1 and wild-type strains. Interestingly, the chronological life span was lowered in the gsh1 strain cultured with 10% glucose but not under dietary restriction. The gsh1 strain also showed inhibition of the mitochondrial respiration in 0.5 and 10% glucose but only increased the H2O2 levels under dietary restriction. These results correlate well with the GSH/GSSG ratio, which showed a decrease in gsh1 strain cultured with 0.5% glucose. Together, these data indicate that glutathione exhaustion impact negatively both the electron transport chain function and the chronological life span of yeast, the latter occurring when a low threshold level of this antioxidant is reached, independently of the H2O2 levels.