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 lifespan 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 ROS generation and glutathione levels, and both chemical species impact in the aging process. Herein, we provide evidence that mutation of the gene GSH1 diminishes glutathione levels. Moreover, glutathione levels were higher with 0.5% than in 10% glucose in the gsh1{Delta} and WT strains. Interestingly, the chronological life span (CLS) was lowered in the gsh1{Delta} strain cultured with 10% glucose but not under dietary restriction. The gsh1{Delta} strain also showed an inhibition of the mitochondrial respiration in 0.5 and 10% of 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{Delta} strain cultured with 0.5% glucose. Altogether these data indicate that glutathione has a major role in the function of electron transport chain (ETC) and is essential to maintain life span of Saccharomyces cerevisiae in 10% glucose.