Authors: Lee SS; Lee RY; Fraser AG; Kamath RS; Ahringer J; Ruvkun G
Abstract: We report a systematic RNA interference (RNAi) screen of 5,690 Caenorhabditis elegans genes for gene inactivations that increase lifespan. We found that genes important for mitochondrial function stand out as a principal group of genes affecting C. elegans lifespan. A classical genetic screen identified a mutation in the mitochondrial leucyl-tRNA synthetase gene (lrs-2) that impaired mitochondrial function and was associated with longer-lifespan. The long-lived worms with impaired mitochondria had lower ATP content and oxygen consumption, but differential responses to free-radical and other stresses. These data suggest that the longer lifespan of C. elegans with compromised mitochrondria cannot simply be assigned to lower free radical production and suggest a more complex coupling of metabolism and longevity.Keywords: Adenosine Triphosphate/metabolism; Animals; Caenorhabditis elegans/cytology/enzymology/*genetics/*metabolism; Gene Expression Regulation; Genes, Helminth/*genetics; Genetic Testing; Leucine-tRNA Ligase/genetics/metabolism; Longevity/*genetics; Mitochondria/enzymology/genetics/*metabolism/pathology; Oxygen Consumption; *RNA Interference; Stress, Physiological/metabolism
Journal: Nature genetics
Date: Nov. 26, 2002
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Lee SS, Lee RY, Fraser AG, Kamath RS, Ahringer J, Ruvkun G (2003) A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity. Nature genetics 33: 40-8.