Worming pathways to and from DAF-16/FOXO

Exp Gerontol. 2006 Oct;41(10):928-34. doi: 10.1016/j.exger.2006.05.020. Epub 2006 Jul 12.


In Caenorhabditis elegans, the insulin/IGF-1 signaling pathway controls many biological processes such as life span, fat storage, dauer diapause, reproduction and stress response . This pathway is comprised of many genes including the insulin/IGF-1 receptor (DAF-2) that signals through a conserved PI 3-kinase/AKT pathway and ultimately down-regulates DAF-16, a forkhead transcription factor (FOXO). DAF-16 also receives input from several other pathways that regulate life span such as the germline and the JNK pathway [Hsin, H., Kenyon, C., 1999. Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399, 362-366; Oh, S.W., Mukhopadhyay, A., Svrzikapa, N., Jiang, F., Davis, R.J., Tissenbaum, H.A., 2005. JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc. Natl. Acad. Sci. USA 102, 4494-4499]. Therefore, DAF-16 integrates signals from multiple pathways and regulates its downstream target genes to control diverse processes. Here, we discuss the signals to and from DAF-16, with a focus on life span regulation.

Publication types

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

MeSH terms

  • Aging / genetics*
  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / genetics*
  • Caloric Restriction
  • Forkhead Transcription Factors / genetics*
  • Gene Expression Regulation, Developmental / genetics
  • Germ Cells / physiology
  • Insulin / genetics
  • Longevity / genetics
  • Models, Genetic
  • Receptor, IGF Type 2 / genetics
  • Receptor, Insulin / genetics
  • Signal Transduction / genetics
  • Sirtuins / genetics
  • Transcription Factors / genetics*


  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Insulin
  • Receptor, IGF Type 2
  • Transcription Factors
  • daf-16 protein, C elegans
  • DAF-2 protein, C elegans
  • Receptor, Insulin
  • SIR-2.1 protein, C elegans
  • Sirtuins