Browsing by Author "Tullet, Jennifer M. A."

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    Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans.
    (2008) Tullet, Jennifer M. A.; Hertweck, Maren; An, Jae Hyung; Baker, Joseph; Hwang, Ji Yun; Liu, Shu; Oliveira, Riva de Paula; Baumeister, Ralf; Blackwell, T. Keith
    Insulin/IGF-1-like signaling (IIS) is central to growth and metabolism and has a conserved role in aging. In C. elegans, reductions in IIS increase stress resistance and longevity, effects that require the IISinhibited FOXO protein DAF-16. The C. elegans transcription factor SKN-1 also defends against oxidative stress bymobilizing the conserved phase 2 detoxification response. Herewe showthat IIS not only opposes DAF-16 but also directly inhibits SKN-1 in parallel. The IIS kinases AKT-1, -2, and SGK-1 phosphorylate SKN-1, and reduced IIS leads to constitutive SKN-1 nuclear accumulation in the intestine and SKN-1 target gene activation. SKN-1 contributes to the increased stress tolerance and longevity resulting from reduced IIS and delays aging when expressed transgenically. Furthermore, SKN-1 that is constitutively active increases life span independently of DAF-16. Our findings indicate that the transcription network regulated by SKN-1 promotes longevity and is an important direct target of IIS.