Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans.

• Author(s): 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
• Date: 2015
• Origin: Oasisbr
• Document Type: Journal article
• Language: English

Description

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.