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. 2005 Jul 1;19(13):1544-55.
doi: 10.1101/gad.1308205.

A systematic RNAi screen for longevity genes in C. elegans

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A systematic RNAi screen for longevity genes in C. elegans

Benjamin Hamilton et al. Genes Dev. .

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.

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Figures

Figure 1.
Figure 1.
RNAi inactivation of multiple candidate longevity genes induces hsp-6::GFP expression. (A) Basal levels of hsp-6::GFP expression in worms treated with control RNAi (L4440 empty vector). (B) Greatly enhanced hsp-6::GFP expression in worms treated with RNAi targeting F26E4.6 (cytochrome C oxidase subunit) (Yoneda et al. 2004). (C) A representative image of enhanced hsp-6::GFP expression in worms treated with a “group 1” RNAi. Group 1 RNAi include F54H12.1, C53B7.4, D2030.4, F26E4.6, F26E4.9, K04G7.4, T20H4.5, and W09C5.8. (D) A representative picture of somewhat enhanced hsp-6::GFP expression in worms treated with a “group 2” RNAi. Group 2 RNAi include B0261.4, C39F7.2, Y53F4B.23, Y75B8A.33, and Y92C3A.1.

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