Genetics · 2008 · 68 citations · 44 references
Life SciencesBiologyGeneticsGene ExpressionReproductive BiologyTranscriptional RegulationDevelopmental Signaling PathwaysLongevityC. Elegans Developmental ModelsFoxo Transcription Factor RegulationFoxo Transcriptional RegulationGerm Cell MaintenanceGonadal Gene RegulationInsulin SignalingInsulin Signaling PathwayLife Span Extension
The two parts of the Caenorhabditis elegans reproductive system, the germ cells and the somatic reproductive tissues, each influence the life span of the animal. Removing the germ cells increases longevity, and this life span extension requires the somatic gonad. Here we show that the somatic gonad and the germ cells make distinct contributions to life span determination. The life span increase produced by loss of the germ cells requires the DAF-16/FOXO transcription factor. In response to germ-cell removal, DAF-16 accumulates in nuclei. We find that the somatic gonad is not required for DAF-16 nuclear accumulation or for the increased stress resistance that is produced by germ-cell removal. The somatic gonad is required, however, for expression of specific DAF-16 target genes. DAF-16 is known to be activated by reduced insulin/IGF-1 signaling in C. elegans. In certain insulin/IGF-1-pathway mutants, the somatic gonad is not required for germ-cell removal to extend life span. Our genetic experiments suggest that these mutations reduce insulin/IGF-1 signaling below a critical threshold level. At these low levels of insulin/IGF-1 signaling, factors normally provided by the somatic gonad are no longer needed for germ-cell removal to increase the expression of DAF-16 target genes.
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THE GENETICS OF <i>CAENORHABDITIS ELEGANS</i>
Sydney Brenner · Genetics · 1974 · 15.5K citations · Full text
Life Sciences, Biology, Genetics +14
A C. elegans mutant that lives twice as long as wild type
Cynthia Kenyon, Jean Chang, Erin Gensch et al. · Nature · 1993 · 3.4K citations
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Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
Coleen T. Murphy, Steven A. McCarroll, Cornelia I. Bargmann et al. · Nature · 2003 · 2.3K citations