An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans.

Authors: Tissenbaum HA; Ruvkun G

Abstract: Mutations in daf-2 and age-1 cause a dramatic increase in longevity as well as developmental arrest at the dauer diapause stage in Caenorhabditis elegans. daf-2 and age-1 encode components of an insulin-like signaling pathway. Both daf-2 and age-1 act at a similar point in the genetic epistasis pathway for dauer arrest and longevity and regulate the activity of the daf-16 gene. Mutations in daf-16 cause a dauer-defective phenotype and are epistatic to the diapause arrest and life span extension phenotypes of daf-2 and age-1 mutants. Here we show that mutations in this pathway also affect fertility and embryonic development. Weak daf-2 alleles, and maternally rescued age-1 alleles that cause life span extension but do not arrest at the dauer stage, also reduce fertility and viability. We find that age-1(hx546) has reduced both maternal and zygotic age-1 activity. daf-16 mutations suppress all of the daf-2 and age-1 phenotypes, including dauer arrest, life span extension, reduced fertility, and viability defects. These data show that insulin signaling, mediated by DAF-2 through the AGE-1 phosphatidylinositol-3-OH kinase, regulates reproduction and embryonic development, as well as dauer diapause and life span, and that DAF-16 transduces these signals. The regulation of fertility, life span, and metabolism by an insulin-like signaling pathway is similar to the endocrine regulation of metabolism and fertility by mammalian insulin signaling.

Keywords: Animals; Caenorhabditis elegans/growth & development/*physiology; *Caenorhabditis elegans Proteins; Fertility/genetics; Genes, Helminth/genetics; Genotype; Helminth Proteins/*genetics; Insulin/metabolism; Longevity/*genetics; Mutation/genetics; Phosphatidylinositol 3-Kinases/metabolism; Receptor, Insulin/*genetics; Recombination, Genetic/genetics; Reproduction/*genetics; Signal Transduction/*physiology; Temperature; Transcription Factors/genetics; Zygote/physiology
Journal: Genetics
Volume: 148
Issue: 2
Pages: 703-17
Date: March 20, 1998
PMID: 9504918
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Tissenbaum HA, Ruvkun G (1998) An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans. Genetics 148: 703-17.

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