Caffeine extends yeast lifespan by targeting TORC1

Mol Microbiol. 2008 Jul;69(1):277-85. doi: 10.1111/j.1365-2958.2008.06292.x. Epub 2008 May 26.

Abstract

Dietary nutrient limitation (dietary restriction) is known to increase lifespan in a variety of organisms. Although the molecular events that couple dietary restriction to increased lifespan are not clear, studies of the model eukaryote Saccharomyces cerevisiae have implicated several nutrient-sensitive kinases, including the target of rapamycin complex 1 (TORC1), Sch9, protein kinase A (PKA) and Rim15. We have recently demonstrated that TORC1 activates Sch9 by direct phosphorylation. We now show that Sch9 inhibits Rim15 also by direct phosphorylation. Treatment of yeast cells with the specific TORC1 inhibitor rapamycin or caffeine releases Rim15 from TORC1-Sch9-mediated inhibition and consequently increases lifespan. This kinase cascade appears to have been evolutionarily conserved, suggesting that caffeine may extend lifespan in other eukaryotes, including man.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caffeine / pharmacology*
  • Gene Expression Regulation, Fungal / drug effects
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Sirolimus / pharmacology*

Substances

  • Saccharomyces cerevisiae Proteins
  • Caffeine
  • Protein Kinases
  • Rim15 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • SCH9 protein, S cerevisiae
  • target of rapamycin protein, S cerevisiae
  • Sirolimus