Regulation of Caenorhabditis elegans RNA Interference by the daf-2 Insulin Stress and Longevity Signaling Pathway

A conserved insulin-like signaling pathway regulatesmetabolism, development, stress resistance, and life spanin Caenorhabditis elegans (Lee et al. 2003). This pathway involves an insulin-like receptor DAF-2, a phosphatidylinositol-3-OH kinase (PI3K) AGE-1, and the kinases AKT-1, AKT-2 (Paradis and Ruvkun 1998), andPDK-1 (Paradis et al. 1999), as well as the fork head transcription factor DAF-16 (Ogg et al. 1997; Lee et al.2003). Loss-of-function mutations in daf-2 or age-1cause the worm to arrest at the dauer diapause stage ratherthan proceeding to reproductive development (Ogg et al.1997). In addition, the daf-2 and age-1 mutants have increased life span and stress resistance, compared withwild type (Ogg et al. 1997; Honda and Honda 2002; Leeet al. 2003). Both the dauer-constitutive and life spanphenotypes of the daf-2 or age-1 mutants are suppressedby loss-of-function mutation in the downstream daf-16gene (Ogg et al. 1997)...