The nematode C. elegans has been a discovery engine for regulation of animal lifespan. We propose to follow up our surprising discovery that decreases in insulin-like signaling induce a dramatic increase in lifespan in C. elegans that is intimately associated with expression of germline-specific pathways in the somatic cells. We will dissect how these genes are regulated by insulin-like signaling and how the somatic expression of germline genes contributes to the increase in longevity. Because essentially all of the genes proposed to be studied in this proposal are conserved in humans, and because the insulin pathway has already been shown to act in human longevity, the pathways we dissect are likely to be applicable to human longevity.
The nematode C. elegans has been a discovery engine for regulation of animal lifespan. Because essentially all of the genes proposed to be studied in this proposal are conserved in humans, and because the insulin pathway has already been shown to act in human longevity, the pathways we dissect are likely to be applicable to human longevity.
|Riedel, Christian G; Dowen, Robert H; Lourenco, Guinevere F et al. (2013) DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity. Nat Cell Biol 15:491-501|
|Wu, Xiaoyun; Shi, Zhen; Cui, Mingxue et al. (2012) Repression of germline RNAi pathways in somatic cells by retinoblastoma pathway chromatin complexes. PLoS Genet 8:e1002542|
|Curran, Sean P; Wu, Xiaoyun; Riedel, Christian G et al. (2009) A soma-to-germline transformation in long-lived Caenorhabditis elegans mutants. Nature 459:1079-84|
|Wang, Meng C; O'Rourke, Eyleen J; Ruvkun, Gary (2008) Fat metabolism links germline stem cells and longevity in C. elegans. Science 322:957-60|
|Samuelson, A V; Klimczak, R R; Thompson, D B et al. (2007) Identification of Caenorhabditis elegans genes regulating longevity using enhanced RNAi-sensitive strains. Cold Spring Harb Symp Quant Biol 72:489-97|
|Curran, Sean P; Ruvkun, Gary (2007) Lifespan regulation by evolutionarily conserved genes essential for viability. PLoS Genet 3:e56|
|Samuelson, Andrew V; Carr, Christopher E; Ruvkun, Gary (2007) Gene activities that mediate increased life span of C. elegans insulin-like signaling mutants. Genes Dev 21:2976-94|
|Li, Weiqing; Kennedy, Scott G; Ruvkun, Gary (2003) daf-28 encodes a C. elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathway. Genes Dev 17:844-58|
|Pierce, S B; Costa, M; Wisotzkey, R et al. (2001) Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. Genes Dev 15:672-86|