title: Genome-wide screen in Saccharomyces cerevisiae identifies vacuolar protein sorting, autophagy, biosynthetic, and tRNA methylation genes involved in life span regulation.
abstract: 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.
authors.affiliation: Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Paola
authors.initials: P
authors.lastname: Fabrizio
authors.forename: Shawn
authors.initials: S
authors.lastname: Hoon
authors.forename: Mehrnaz
authors.initials: M
authors.lastname: Shamalnasab
authors.forename: Abdulaye
authors.initials: A
authors.lastname: Galbani
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Guri
authors.initials: G
authors.lastname: Giaever
authors.forename: Corey
authors.initials: C
authors.lastname: Nislow
authors.forename: Valter D
authors.initials: VD
authors.lastname: Longo
mesh_terms: D000375:Aging / Q000235:genetics; D001343:Autophagy; D017353:Gene Deletion; D016681:Genome, Fungal; D008136:Longevity / Q000235:genetics*; D008745:Methylation; D008928:Mitochondria; D014176:Protein Biosynthesis; D021381:Protein Transport; D012343:RNA, Transfer / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology; D014617:Vacuoles / Q000378:metabolism
chemical_list: D012343:RNA, Transfer