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RESEARCH PAPER
1 Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850, USA; 2 Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA
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: Longevity; aging; C. elegans; insulin signaling; RNAi screen; genomic]
Received February 22, 2005; revised version accepted May 19, 2005.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1308205.
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.
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