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

Abstract

SummaryBudding 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 ∆ ∆ ∆ ∆ pka1∆ ∆ ∆ ∆ sck2 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.

The Fission Yeastphp2Mutant Displays a Lengthened Chronological Lifespan

“…3) In the fission yeast Schizosaccharomyces pombe, disruption of pka1 þ and sck2 þ has been reported to increase chronological lifespan. 4) The lifespan of S. pombe can also be extended by calorie restriction (CR), which is known to extend the lifespan of various organisms from yeast to mammals. This process relies on the Sty1 MAP kinase in S. pombe.…”

Identification of Ecl Family Genes That Extend Chronological Lifespan in Fission Yeast

“…The factors known to be involved in lifespan regulation in S. pombe are Sck2 and Pka1. 19) These are known to function as negative factors in the extension of chronological lifespan in separate (redundant or parallel signalling) ways. Recently, respiration-defective mutants were reported to have short chronological lifespans.…”

Identification of a Fatty Acyl-CoA Synthetase Gene,lcf2+, Which Affects Viability after Entry into the Stationary Phase inSchizosaccharomyces pombe

“…13,14) In S. pombe, it is known that chronological aging is accelerated by glucose signaling, because cells bearing mutations in genes controlling this pathway, such as pka1 and sck2, live longer. 15) In S. cerevisiae, it is also known that deletion of genes SCH9, CYR1, and RAS2, which mediate glucose signaling, extends chronological lifespan. 13,14) In this study, we determined that Álcf2 mutants lived longer than wild-type cells after entry into the stationary phase in SD medium.…”