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A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity.

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.

Pubmed ID: 12447374


  • Lee SS
  • Lee RY
  • Fraser AG
  • Kamath RS
  • Ahringer J
  • Ruvkun G


Nature genetics

Publication Data

January 1, 2003

Associated Grants

  • Agency: Wellcome Trust, Id: 054523

Mesh Terms

  • Adenosine Triphosphate
  • Animals
  • Caenorhabditis elegans
  • Gene Expression Regulation
  • Genes, Helminth
  • Genetic Testing
  • Leucine-tRNA Ligase
  • Longevity
  • Mitochondria
  • Oxygen Consumption
  • RNA Interference
  • Stress, Physiological