Title | Tissue entrainment by feedback regulation of insulin gene expression in the endoderm of Caenorhabditis elegans. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Murphy CT, Lee S-J, Kenyon C |
Journal | Proc Natl Acad Sci U S A |
Volume | 104 |
Issue | 48 |
Pagination | 19046-50 |
Date Published | 2007 Nov 27 |
ISSN | 1091-6490 |
Keywords | Aging, Animals, Animals, Genetically Modified, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Endoderm, Feedback, Physiological, Forkhead Transcription Factors, Insulin, Intestines, Larva, Longevity, Peptide Hormones, Recombinant Fusion Proteins, Signal Transduction, Superoxide Dismutase, Transcription Factors |
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. |
DOI | 10.1073/pnas.0709613104 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
Full Text | |
PubMed ID | 18025456 |
PubMed Central ID | PMC2141905 |
Grant List | R01 AG011816 / AG / NIA NIH HHS / United States R01 AG11816 / AG / NIA NIH HHS / United States |