A Systematic RNAi Screen Identifies a Critical Role for Mitochondria in C. Elegans Longevity

Nat Genet. 2003 Jan;33(1):40-8. doi: 10.1038/ng1056. Epub 2002 Nov 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism*
  • Gene Expression Regulation
  • Genes, Helminth / genetics*
  • Genetic Testing
  • Leucine-tRNA Ligase / genetics
  • Leucine-tRNA Ligase / metabolism
  • Longevity / genetics*
  • Mitochondria / enzymology
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Oxygen Consumption
  • RNA Interference*
  • Stress, Physiological / metabolism

Substances

  • Adenosine Triphosphate
  • Leucine-tRNA Ligase