LET-60 RAS modulates effects of insulin/IGF-1 signaling on development and aging in Caenorhabditis elegans.

Authors: Nanji M; Hopper NA; Gems D

Abstract: The DAF-2 insulin/insulin-like growth factor 1 (IGF-1) receptor signals via a phosphatidylinositol 3-kinase (PI3K) pathway to control dauer larva formation and adult longevity in Caenorhabditis elegans. Yet epistasis analysis suggests signal bifurcation downstream of DAF-2. We have used epistasis analysis to test whether the Ras pathway (which plays a role in signaling from mammalian insulin receptors) acts downstream of DAF-2. We find that an activated Ras mutation, let-60(n1046gf), weakly suppresses constitutive dauer diapause in daf-2 and age-1 (PI3K) mutants. Moreover, increased Ras pathway signaling partially suppresses the daf-2 mutant feeding defect, while reduced Ras pathway signaling enhances it. By contrast, activated Ras extends the longevity induced by mutation of daf-2, while reduced Ras pathway signaling partially suppresses it. Thus, Ras pathway signaling appears to act with insulin/IGF-1 signaling during larval development, but against it during aging.

Keywords: Aging/*physiology; Animals; Caenorhabditis elegans/genetics/growth & development/*physiology; Caenorhabditis elegans Proteins/genetics/*metabolism; Epistasis, Genetic; Inositol 1,4,5-Trisphosphate/metabolism; Insulin/*metabolism; Insulin-Like Growth Factor I/*metabolism; Longevity; Models, Animal; Phenotype; Phosphatidylinositol 3-Kinases/metabolism; Receptor, Insulin/genetics/*metabolism; Signal Transduction/*physiology; ras Proteins/genetics/*metabolism
Journal: Aging cell
Volume: 4
Issue: 5
Pages: 235-45
Date: Sept. 17, 2005
PMID: 16164423
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Citation:

Nanji M, Hopper NA, Gems D (2005) LET-60 RAS modulates effects of insulin/IGF-1 signaling on development and aging in Caenorhabditis elegans. Aging cell 4: 235-45.


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