Life span modulation by ALT1, alanine-metabolizing enzyme, in Saccharomyces cerevisiae

초록

Importance of alterations in metabolic pathways has been implicated as important factors affecting life span. However, the determination of specific pathways and enzymes involved in life span remain largely unexplored. Meanwhile, caloric restriction (CR) has been known to extend life span of many species. In yeast, CR extends both replicative life span and chronological life span. Using metabolomics and genetic approaches, we identified metabolites affecting CR-induced chronological life span in yeast, Saccharomyces cerevisiae. Among 23 metabolites with altered profile by CR, we found that alanine level is inversely correlated with yeast chronological life span. Later analysis using deletion mutant of ALT1, the gene encoding the major alanine transaminase, revealed that life span modulation by ALT1 is TOR1-independent. Further studies showed that alt1Δ completely suppresses cytochrome C oxidase subunit 2 expression. This study shows the importance of small molecule metabolism and relevance of metabolomics combined with genetic approach in the mechanistic studies in life span.