The Ras and Sch9 pathways regulate stress resistance and longevity

Exp Gerontol. 2003 Jul;38(7):807-11. doi: 10.1016/s0531-5565(03)00113-x.


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.

MeSH terms

  • DNA-Binding Proteins / metabolism
  • Gene Deletion
  • Genes, ras*
  • Longevity / genetics
  • Oxidation-Reduction
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction / physiology*
  • Superoxide Dismutase / metabolism
  • Transcription Factors / metabolism
  • Yeasts / physiology*


  • DNA-Binding Proteins
  • MSN2 protein, S cerevisiae
  • MSN4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Superoxide Dismutase
  • superoxide dismutase 2
  • Protein Kinases
  • SCH9 protein kinase