Cell Reports
Volume 3, Issue 1, 31 January 2013, Pages 79-91
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Article
A Fasting-Responsive Signaling Pathway that Extends Life Span in C. elegans

https://doi.org/10.1016/j.celrep.2012.12.018Get rights and content
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Summary

Intermittent fasting is one of the most effective dietary restriction regimens that extend life span in C. elegans and mammals. Fasting-stimulus responses are key to the longevity response; however, the mechanisms that sense and transduce the fasting stimulus remain largely unknown. Through a comprehensive transcriptome analysis in C. elegans, we find that along with the FOXO transcription factor DAF-16, AP-1 (JUN-1/FOS-1) plays a central role in fasting-induced transcriptional changes. KGB-1, one of the C. elegans JNKs, acts as an activator of AP-1 and is activated in response to fasting. KGB-1 and AP-1 are involved in intermittent fasting-induced longevity. Fasting-induced upregulation of the components of the SCF E3 ubiquitin ligase complex via AP-1 and DAF-16 enhances protein ubiquitination and reduces protein carbonylation. Our results thus identify a fasting-responsive KGB-1/AP-1 signaling pathway, which, together with DAF-16, causes transcriptional changes that mediate longevity, partly through regulating proteostasis.

Highlights

► JNK/AP-1 signaling and DAF-16 play a central role in fasting-stimulus responses ► AP-1 and DAF-16 mediate induction of fasting genes that play key roles in life-span extension ► The SCF E3 ubiquitin ligase complex is a target of fasting-responsive signaling ► Fasting enhances protein ubiquitination, causing a reduction in protein carbonylation

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