Two neurons mediate diet-restriction-induced longevity in C. elegans

Nature. 2007 May 31;447(7144):545-9. doi: 10.1038/nature05904.


Dietary restriction extends lifespan and retards age-related disease in many species and profoundly alters endocrine function in mammals. However, no causal role of any hormonal signal in diet-restricted longevity has been demonstrated. Here we show that increased longevity of diet-restricted Caenorhabditis elegans requires the transcription factor gene skn-1 acting in the ASIs, a pair of neurons in the head. Dietary restriction activates skn-1 in these two neurons, which signals peripheral tissues to increase metabolic activity. These findings demonstrate that increased lifespan in a diet-restricted metazoan depends on cell non-autonomous signalling from central neuronal cells to non-neuronal body tissues, and suggest that the ASI neurons mediate diet-restriction-induced longevity by an endocrine mechanism.

MeSH terms

  • Animals
  • Caenorhabditis elegans / anatomy & histology
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Caloric Restriction*
  • Cell Respiration
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Diet
  • Head
  • Longevity / physiology*
  • Models, Biological
  • Neurons / metabolism*
  • Oxygen Consumption
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Transcription Factors
  • skn-1 protein, C elegans