A fasting-responsive signaling pathway that extends life span in C. elegans.

Masaharu Uno, Sakiko Honjoh, Mitsuhiro Matsuda, Haruka Hoshikawa, Saya Kishimoto, Tomohito Yamamoto, Miki Ebisuya, Takuya Yamamoto, Kunihiro Matsumoto, Eisuke Nishida

Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.

Cell reports 2013 Jan 31

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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. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Masaharu Uno, Sakiko Honjoh, Mitsuhiro Matsuda, Haruka Hoshikawa, Saya Kishimoto, Tomohito Yamamoto, Miki Ebisuya, Takuya Yamamoto, Kunihiro Matsumoto, Eisuke Nishida. A fasting-responsive signaling pathway that extends life span in C. elegans. Cell reports. 2013 Jan 31;3(1):79-91