A fasting-responsive signaling pathway that extends life span in C. elegans.
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.
Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Masaharu
M
Uno
Sakiko
S
Honjoh
Mitsuhiro
M
Matsuda
Haruka
H
Hoshikawa
Saya
S
Kishimoto
Tomohito
T
Yamamoto
Miki
M
Ebisuya
Takuya
T
Yamamoto
Kunihiro
K
Matsumoto
Eisuke
E
Nishida
D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D005215:Fasting; D051858:Forkhead Transcription Factors; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008136:Longevity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D019089:Stem Cell Factor / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D019089:Stem Cell Factor; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D044767:Ubiquitin-Protein Ligases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases