Tissue entrainment by feedback regulation of insulin gene expression in the endoderm of Caenorhabditis elegans.
How are the rates of aging of different tissues coordinated? In Caenorhabditis elegans, decreasing insulin/IGF-1 signaling extends lifespan by activating the transcription factor DAF-16/FOXO. If DAF-16 levels are experimentally increased in one tissue, such as the intestine, DAF-16 activity in other tissues rises. Here we test the hypothesis that this "FOXO-to-FOXO" signaling occurs via feedback regulation of ins-7 insulin gene expression. We find that DAF-16 regulates ins-7 expression in the intestine, and that preventing this regulation blocks FOXO-to-FOXO signaling from the intestine to other tissues. Our findings show that feedback regulation of insulin gene expression coordinates DAF-16 activity among the tissues, and they establish the intestine, which is the animal's entire endoderm, as an important insulin-signaling center.
Murphy
Coleen T
CT
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-2200, USA.
Lee
Seung-Jae
SJ
Kenyon
Cynthia
C
D000375:Aging / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004707:Endoderm / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology*; D051858:Forkhead Transcription Factors; D007328:Insulin / Q000502:physiology*; D007422:Intestines / Q000502:physiology*; D007814:Larva; D008136:Longevity / Q000235:genetics; D036361:Peptide Hormones / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; C525653:Ins-7 protein, C elegans; D007328:Insulin; D036361:Peptide Hormones; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C525107:Sod-3 protein, C elegans; D013482:Superoxide Dismutase