A Measurable Increase in Oxidative Damage Due to Reduction in Superoxide Detoxification Fails to Shorten the Life Span of Long-Lived Mitochondrial Mutants of Caenorhabditis elegans

• Published in: Genetics (Austin) Vol. 177; no. 4; pp. 2063 - 2074
• Main Authors: Yang, Wen, Li, Jingjing, Hekimi, Siegfried
• Format: Journal Article
• Language: English
• Published: United States Genetics Soc America 01.12.2007; Genetics Society of America
• Subjects: Aging; Animals; Caenorhabditis elegans - genetics; Caenorhabditis elegans - physiology; Genes, Mitochondrial; Genetic engineering; Investigations; Iron-sulfur proteins; Longevity - genetics; Mutation; Organisms; Oxidative Stress; Studies; Superoxide Dismutase - analysis; Superoxide Dismutase-1; Superoxides - metabolism; Transgenic animals
• ISSN: 0016-6731; 1943-2631; 1943-2631
• DOI: 10.1534/genetics.107.080788

SOD-1 and SOD-2 detoxify superoxide in the cytoplasm and mitochondria. We find that, although several long-lived mutants of Caenorhabditis elegans have increased SOD levels, this phenomenon does not correlate with life span or growth rate. Furthermore, although disruption of sod-1 or -2 expression produces numerous phenotypes, including increased sensitivity to paraquat and increased oxidative damage to proteins (except in daf-2 mutants), this fails to shorten the life span of these long-lived mutants. In fact, sod-1(RNAi) increases the life span of daf-2 mutants and sod-2(RNAi) that of clk-1 mutants. Our results suggest that increased superoxide detoxification and low oxidative damage are not crucial for the longevity of the mutants examined, with the possible exception of daf-2, where our results are inconclusive. These results are surprising because several of the long-lived mutants that we examined specifically affect mitochondrial electron transport, a process whose involvement in life-span determination is believed to be related to superoxide generation. We discuss the significance of our findings in light of the oxidative stress theory of aging.