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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

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.

Details

Original languageEnglish
Pages (from-to)79-91
Number of pages13
JournalCell reports
Volume3
Issue number1
Publication statusPublished - 31 Jan 2013
Peer-reviewedYes

External IDs

Scopus 84873121957

Keywords

Keywords

  • Animals, Caenorhabditis elegans/drug effects, Caenorhabditis elegans Proteins/metabolism, Fasting, Forkhead Transcription Factors, Gene Expression Profiling, Gene Expression Regulation/drug effects, JNK Mitogen-Activated Protein Kinases/metabolism, Longevity/drug effects, Signal Transduction/drug effects, Stem Cell Factor/metabolism, Transcription Factor AP-1/metabolism, Transcription Factors/metabolism, Transcription, Genetic/drug effects, Ubiquitin-Protein Ligases/metabolism, p38 Mitogen-Activated Protein Kinases/metabolism