Exogenous alanine supplements modulates yeast chronological life span

초록

We previously identified a role of yeast ALT1, the gene encoding the major alanine transaminase, in lifespan modulation. In yeast, alanine level is correlated with yeast chronological lifespan. In the calorie restriction condition, chronological lifespan (CLS) is increased and alanine level is drastically decreased. Genetic analysis using alt1 deletion mutant revealed that ALT1 gene is required for normal lifespan of yeast in TOR1-independent manner. The alt1Δ mutant had significantly higher alanine levels compared to the WT. In addition, the change of the alanine level was much higher in the calorie restriction condition (Control group, 59.7% and CR group, 176.1%). These results indicate that ALT1 is involved in the catabolic pathway of alanine and that the decrease in alanine level in the long-living group may be the results of ALT1 modulation in the CR condition. In this study, we verified the effect of exogenous alanine level in yeast CLS. We supplemented various level of exogenous alanine to culture medium and examined the cell growth and CLS. Cell growth was inhibited and CLS was decreased by exogenous alanine supplement in dose-dependent manner. In addition, growing cells in the presence of ALT inhibitors slightly increased CLS. These results verifies that ALT1 regulates yeast CLS by modulating alanine level in the cell.