Regulation of C. elegans life-span by insulinlike signaling in the nervous system.
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.
Wolkow
C A
CA
Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Kimura
K D
KD
Lee
M S
MS
Ruvkun
G
G
D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000502:physiology; D007814:Larva / Q000502:physiology; D008136:Longevity; D009132:Muscles / Q000166:cytology / Q000502:physiology; D009424:Nervous System Physiological Phenomena; D009474:Neurons / Q000502:physiology*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases; D011401:Promoter Regions, Genetic; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D011993:Recombinant Fusion Proteins; D002374:Catalase; D013482:Superoxide Dismutase; D019869:Phosphatidylinositol 3-Kinases; C100662:AGE-1 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin