Genome-Wide Screen in Saccharomyces cerevisiae Identifies Vacuolar Protein Sorting, Autophagy, Biosynthetic, and tRNA Methylation Genes Involved in Life Span Regulation

The study of the chronological life span of Saccharomyces cerevisiae, which measures the survival of populations of non-dividing yeast, has resulted in the identification of homologous genes and pathways that promote aging in organisms ranging from yeast to mammals. Using a competitive genome-wide approach, we performed a screen of a complete set of approximately 4,800 viable deletion mutants to identify genes that either increase or decrease chronological life span. Half of the putative short-/long-lived mutants retested from the primary screen were confirmed, demonstrating the utility of our approach. Deletion of genes involved in vacuolar protein sorting, autophagy, and mitochondrial function shortened life span, confirming that respiration and degradation processes are essential for long-term survival. Among the genes whose deletion significantly extended life span are ACB1, CKA2, and TRM9, implicated in fatty acid transport and biosynthesis, cell signaling, and tRNA methylation, respectively. Deletion of these genes conferred heat-shock resistance, supporting the link between life span extension and cellular protection observed in several model organisms. The high degree of conservation of these novel yeast longevity determinants in other species raises the possibility that their role in senescence might be conserved

A Possible Role of the Creatine Phosphate-Creatine Pool in the Regulation of the Adenylate Pool

Human lymphoblastoid Raji cells and mouse hybridoma ascites cells incubated with 20 mM creatine showed significant increases in creatine, creatine phosphate and adenine nucleotide levels and in the energy charge. In human erythrocytes in which no variation of the creatine phosphate-creatine pool was observed because of a very low creatine kinase activity, the adenine nucleotide pool and the energy charge were not modified. These observations suggest not only a relationship among the creatine phosphate-creatine pool, the energy charge and the adenylate pool, but also the possibility to increase the energy charge and the adenylate pool in cells with creatine kinase activity by expanding the creatine phosphate-creatine pool