Regulation of chronological aging in Schizosaccharomyces pombe by the protein kinases Pka1 and Sck2.
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.
Roux
Antoine E
AE
Department of Biochemistry, Université de Montréal, Montréal, Québec, Canada HC3 3J7.
Quissac
Aurélie
A
Chartrand
Pascal
P
Ferbeyre
Gerardo
G
Rokeach
Luis A
LA
D000375:Aging; D017209:Apoptosis; D002453:Cell Cycle; D002470:Cell Survival; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D018869:Heat-Shock Response / Q000235:genetics; D008136:Longevity / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics*; D015398:Signal Transduction
D017382:Reactive Oxygen Species; D029702:Schizosaccharomyces pombe Proteins; C113036:Sck2 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases