A systematic RNAi screen for longevity genes in C. elegans

  1. Benjamin Hamilton1,
  2. Yuqing Dong1,
  3. Mami Shindo1,
  4. Wenyu Liu1,
  5. Ian Odell1,
  6. Gary Ruvkun2,3,4, and
  7. Siu Sylvia Lee1,3,5
  1. 1Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850, USA; 2Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA

Abstract

We report here the first genome-wide functional genomic screen for longevity genes. We systematically surveyed Caenorhabditis elegans genes using large-scale RNA interference (RNAi), and found that RNAi inactivation of 89 genes extend C. elegans lifespan. Components of the daf-2/insulin-like signaling pathway are recovered, as well as genes that regulate metabolism, signal transduction, protein turnover, and gene expression. Many of these candidate longevity genes are conserved across animal phylogeny. Genetic interaction analyses with the new longevity genes indicate that some act upstream of the daf-16/FOXO transcription factor or the sir2.1 protein deacetylase, and others function independently of daf-16/FOXO and sir2.1, and might define new pathways to regulate lifespan.

Keywords

Footnotes

  • Supplemental material is available at http://www.genesdev.org.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1308205.

  • Corresponding authors.

  • 3 These authors contributed equally to this work.

  • 4 E-MAIL ruvkun{at}molbio.mgh.harvard.edu; FAX (617) 726-5937.

  • 5 E-MAIL SSL29{at}cornell.edu; FAX (607) 255-6249.

    • Accepted May 19, 2005.
    • Received February 22, 2005.
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