A mitochondrial superoxide dismutase (SOD2) is the first line of antioxidant defense against mitochondrial superoxide. Even though the involvement of SOD2 in lifespan has been studied extensively in several organisms, characterization of the aging process has not been performed for the sod2 mutant (sod2D) of a prominent model Schizosaccharomyces pombe. In this study, we measured the chronological lifespan of sod2D cells by their ability to survive in long-term culture. SOD2 deficiency drastically decreased cell viability in the stationary phase. The mutation frequency of nuclear DNA in sod2D was elevated in the stationary phase, and cellular proteins and nuclear DNA were extensively degraded, concurrent with cell death. The sod2 gene in wild-type cells could be induced by an increase in endogenous oxidative stresses, after which, SOD2 activity was substantially elevated during the stationary phase. Culture in a lower glucose concentration (calorie restriction) prominently extended the sod2D lifespan. Therefore, S. pombe SOD2 plays a critical role in longevity through its upregulation in the nondividing phase.
Defects of genome maintenance may causally contribute to aging. In general, base excision repair (BER) is involved in the repair of subtle base lesions and AP sites, and bulky helix-distorting lesions are restored by nucleotide excision repair (NER). Here, we measured the chronological lifespan (CLS) of BER- and NER-deficient mutants of the fission yeast Schizosaccharomyces pombe, and observed the aging process of cells. The CLS of the nth1 (gene for DNA glycosylase/AP lyase) mutant and the rad16 (a homolog of human XPF) mutant were slightly shorter than that of the wild-type (WT) strain. However, survival of the nth1Δ rad16Δ double mutant was significantly reduced after entry into the stationary phase. Deletion of rad16 in an AP endonuclease mutant apn2Δ also accelerated chronological aging. These results indicate that BER and NER synergistically contribute to genome maintenance in non-dividing cells. Reactive oxygen species (ROS) accumulated in cells during the stationary phase, and nth1Δ rad16Δ cells produced more ROS than WT cells. High mutation frequencies and nuclear DNA fragmentation were observed in nth1Δ rad16Δ stationary-phase cells concurrent with apoptotic-like cell death. Calorie restriction significantly reduced the level of ROS in the stationary phase and extended the CLS of nth1Δ rad16Δ cells. Therefore, ROS production critically affects the survival of the DNA repair mutant during chronological aging.
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