Regulation of chronological aging in Schizosaccharomyces pombe by the protein kinases Pka1 and Sck2

Aging Cell. 2006 Aug;5(4):345-57. doi: 10.1111/j.1474-9726.2006.00225.x. Epub 2006 Jul 5.

Abstract

Budding yeast shows a progressive decline in viability after entering stationary phase, a phenomenon known as chronological aging. We show here that the fission yeast Schizosaccharomyces pombe also undergoes chronological aging and that the process is regulated by genes controlling two related nutrient signalling pathways. The first pathway includes the serine/threonine cAMP-activated protein kinase Pka1 and the second pathway comprises the serine/threonine kinase Sck2, a homologue of Saccharomyces cerevisiae SCH9. A double mutant for pka1 and sck2 displayed an additive effect on prolonging the fission yeast lifespan, suggesting that these genes regulate related but independent pathways. These long-lived mutants also accumulated less reactive oxygen species and had a delayed initiation of apoptosis compared with wild-type cells. We also found that strains carrying pka1 deletion but not those with sck2 deletion gained resistance to oxidative stress due to exposure to H(2)O(2) or menadione. On the other hand, the additional increase in lifespan shown by the Deltapka1Deltasck2 double-mutant strain correlated with an increased resistance to both oxidative stress and heat shock. These results underscore the importance of nutrient signalling pathways and reactive oxygen species on organismal lifespan and establish S. pombe as a new model organism to study the molecular mechanisms underlying aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Apoptosis
  • Cell Cycle
  • Cell Survival
  • Cyclic AMP-Dependent Protein Kinases / genetics*
  • Gene Expression Regulation, Fungal
  • Heat-Shock Response / genetics
  • Longevity / genetics
  • Protein-Serine-Threonine Kinases / genetics*
  • Reactive Oxygen Species / metabolism
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / physiology*
  • Schizosaccharomyces pombe Proteins / genetics*
  • Signal Transduction

Substances

  • Reactive Oxygen Species
  • Schizosaccharomyces pombe Proteins
  • Sck2 protein, S pombe
  • Protein-Serine-Threonine Kinases
  • Cyclic AMP-Dependent Protein Kinases