Mitochondrial and Cytoplasmic ROS Have Opposing Effects on Lifespan
The accumulation of oxidative damage caused by reactive oxygen species (ROS) has been proposed to be one of the main causes of aging. However, recent work indicates that low levels of ROS can be beneficial and promote longevity. In this paper, we use a long-lived mitochondrial mutant C. elegans strain clk-1 to further examine the relationship between ROS and lifespan. While it was originally believed that clk-1 mutants had increased lifespan as a result of decreased ROS production, ROS levels have been shown to be increased in clk-1 worms. We show that this increase in ROS is required for the longevity of clk-1 worms as treatment with antioxidants decreases clk-1 lifespan. Further, by using a genetic approach to increase ROS in specific subcellular compartments, we show that the location of the ROS is crucial in determining its effect on lifespan. Increasing ROS in the mitochondria markedly increases clk-1 lifespan, while increasing ROS in the cytoplasm decreases it. Finally, we show that the effect of increased ROS on stress resistance and physiologic rates is also dependent on the location of ROS within the cell but that both of these factors can be experimentally dissociated from lifespan.
Vyšlo v časopise:
Mitochondrial and Cytoplasmic ROS Have Opposing Effects on Lifespan. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004972
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1004972
Souhrn
The accumulation of oxidative damage caused by reactive oxygen species (ROS) has been proposed to be one of the main causes of aging. However, recent work indicates that low levels of ROS can be beneficial and promote longevity. In this paper, we use a long-lived mitochondrial mutant C. elegans strain clk-1 to further examine the relationship between ROS and lifespan. While it was originally believed that clk-1 mutants had increased lifespan as a result of decreased ROS production, ROS levels have been shown to be increased in clk-1 worms. We show that this increase in ROS is required for the longevity of clk-1 worms as treatment with antioxidants decreases clk-1 lifespan. Further, by using a genetic approach to increase ROS in specific subcellular compartments, we show that the location of the ROS is crucial in determining its effect on lifespan. Increasing ROS in the mitochondria markedly increases clk-1 lifespan, while increasing ROS in the cytoplasm decreases it. Finally, we show that the effect of increased ROS on stress resistance and physiologic rates is also dependent on the location of ROS within the cell but that both of these factors can be experimentally dissociated from lifespan.
Zdroje
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Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
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