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

Coleen T. Murphy, Seung Jae Lee, Cynthia Kenyon

Research output: Contribution to journalArticle

109 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)19046-19050
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number48
DOIs
StatePublished - Nov 27 2007

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Aging
  • DAF-16
  • DAF-2
  • FOXO

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