title: The Ras and Sch9 pathways regulate stress resistance and longevity.
abstract: Depending on the availability of extracellular nutrients, yeast can enter either high or low metabolism survival phases. We have identified two pathways that regulate longevity and stress resistance in both the low and high metabolism phases. The deletion of SCH9, which encodes for a serine threonine kinase, triples the mean life span and increases resistance to oxidative and thermal stress. Mutations that decrease the activity of the Ras/Cyr1/PKA pathway also extend longevity and increase stress resistance by activating transcription factors Msn2/Msn4 and the mitochondrial antioxidant enzyme superoxide dismutase (Sod2). Although only one intracellular pathway that includes genes homologous to SCH9 and SOD2 has been identified in worms, our studies in yeast suggest that longevity in higher eukaryotes may also be negatively regulated by the Ras pathway.
authors.affiliation: Division of Biogerontology and Department of Biological Sciences, Andrus Gerontology Center, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA. vlongo@usc.edu
authors.forename: Valter D
authors.initials: VD
authors.lastname: Longo
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism; D017353:Gene Deletion; D011905:Genes, ras; D008136:Longevity / Q000235:genetics; D010084:Oxidation-Reduction; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015003:Yeasts / Q000502:physiology*; D000099156:Superoxide Dismutase 2
chemical_list: D004268:DNA-Binding Proteins; D011494:Protein Kinases; D029701:Saccharomyces cerevisiae Proteins; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2; C081935:MSN2 protein, S cerevisiae; C081937:MSN4 protein, S cerevisiae; C071569:SCH9 protein kinase