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Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):19046-50. Epub 2007 Nov 19.

Tissue entrainment by feedback regulation of insulin gene expression in the endoderm of Caenorhabditis elegans.

Author information

1
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-2200, USA.

Abstract

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.

PMID:
18025456
PMCID:
PMC2141905
DOI:
10.1073/pnas.0709613104
[Indexed for MEDLINE]
Free PMC Article

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