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

Cell Rep. 2013 Jan 31;3(1):79-91. doi: 10.1016/j.celrep.2012.12.018. Epub 2013 Jan 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / physiology*
  • 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
  • Longevity / genetics
  • Longevity / physiology*
  • 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


  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Stem Cell Factor
  • Transcription Factor AP-1
  • Transcription Factors
  • daf-16 protein, C elegans
  • Ubiquitin-Protein Ligases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases

Associated data

  • GEO/GSE27677
  • GEO/GSE42689