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Impaired respiration is positively correlated with decreased life span in Caenorhabditis elegans models of Friedreich Ataxia

Kim Zarse^*,1, Tim J. Schulz^*,,1, Marc Birringer^* and Michael Ristow^*,,2

^* Department of Human Nutrition, Institute of Nutrition, University of Jena, Jena, Germany; and

German Institute of Human Nutrition, Nuthetal, Germany

²Correspondence: Department of Human Nutrition, Inst. of Nutrition, University of Jena, 29 Dornburger St., Jena D-07743, Germany. E-mail: mristow{at}mristow.org

Impaired expression of mitochondrial genes causes alterations in life span of the nematode Caenorhabditis elegans. Intriguingly, although some of these genes have been shown to extend life expectancy and reduce aging processes, others are known to shorten life span in the same model organism. Reduced expression of a mitochondrial protein called frataxin causes a neurodegenerative disorder named Friedreich Ataxia, which decreases life span in humans. Surprisingly, reduced expression of the C. elegans frataxin homologue frh-1 has been associated with both increased as well as decreased life span by different laboratories. To further elucidate these conflicting findings, here we show that different RNA interference (RNAi) constructs directed against frh-1 reduce C. elegans life span. Moreover, we show that frh-1-inhibiting RNAi impairs oxygen consumption and that respiratory rate is positively correlated with life span in this multicellular eukaryote (r=0.8566), suggesting that >73% of life span variance in C. elegans is explained by changes in respiratory rate. Taken together, impaired mitochondrial metabolism due to RNAi-mediated inhibition of the frataxin homologue frh-1 causes both impaired respiration as well as decreased life span in the multicellular eukaryote C. elegans.—Zarse, K., Schulz, T. J., Birringer, M., Ristow, M. Impaired respiration is positively correlated with decreased life span in Caenorhabditis elegans models of Friedreich Ataxia.

Key Words: mitochondria • oxygen • frataxin • hormesis