Publication Date:
2000-10-06
Description:
An insulinlike signaling pathway controls Caenorhabditis elegans aging, metabolism, and development. Mutations in the daf-2 insulin receptor-like gene or the downstream age-1 phosphoinositide 3-kinase gene extend adult life-span by two- to threefold. To identify tissues where this pathway regulates aging and metabolism, we restored daf-2 pathway signaling to only neurons, muscle, or intestine. Insulinlike signaling in neurons alone was sufficient to specify wild-type life-span, but muscle or intestinal signaling was not. However, restoring daf-2 pathway signaling to muscle rescued metabolic defects, thus decoupling regulation of life-span and metabolism. These findings point to the nervous system as a central regulator of animal longevity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolkow, C A -- Kimura, K D -- Lee, M S -- Ruvkun, G -- AG14161/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2000 Oct 6;290(5489):147-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11021802" target="_blank"〉PubMed〈/a〉
Keywords:
Aging/genetics/*physiology
;
Animals
;
Caenorhabditis elegans/genetics/*physiology
;
*Caenorhabditis elegans Proteins
;
Catalase/genetics/metabolism
;
Gene Expression Regulation
;
Genes, Helminth
;
Helminth Proteins/genetics/metabolism
;
Intestines/cytology/physiology
;
Larva/physiology
;
Longevity
;
Muscles/cytology/physiology
;
Nervous System Physiological Phenomena
;
Neurons/*physiology
;
Phenotype
;
*Phosphatidylinositol 3-Kinases
;
Promoter Regions, Genetic
;
Receptor, Insulin/genetics/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
*Signal Transduction
;
Superoxide Dismutase/genetics/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics