Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression

Cell Metab. 2009 Nov;10(5):379-91. doi: 10.1016/j.cmet.2009.10.003.


Many studies have addressed the effect of dietary glycemic index on obesity and diabetes, but little is known about its effect on life span itself. We found that adding a small amount of glucose to the medium (2%) shortened the life span of C. elegans by inhibiting the activities of life span-extending transcription factors that are also inhibited by insulin signaling: the FOXO family member DAF-16 and the heat shock factor HSF-1. This effect involved the downregulation of an aquaporin glycerol channel, aqp-1. We show that changes in glycerol metabolism are likely to underlie the life span-shortening effect of glucose and that aqp-1 may act cell nonautonomously as a feedback regulator in the insulin/IGF-1-signaling pathway. Insulin downregulates similar glycerol channels in mammals, suggesting that this glucose-responsive pathway might be conserved evolutionarily. Together, these findings raise the possibility that a low-sugar diet might have beneficial effects on life span in higher organisms.

Publication types

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

MeSH terms

  • Animals
  • Aquaporin 1 / antagonists & inhibitors
  • Aquaporin 1 / genetics
  • Aquaporin 1 / metabolism*
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / antagonists & inhibitors
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation
  • Feedback, Physiological
  • Forkhead Transcription Factors
  • Gene Knockout Techniques
  • Glucose / metabolism*
  • Glycerol / metabolism
  • Heat Shock Transcription Factors
  • Insulin / metabolism
  • Longevity
  • Receptor, IGF Type 1 / physiology
  • Signal Transduction*
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Heat Shock Transcription Factors
  • Insulin
  • Transcription Factors
  • aqp-1 protein, C elegans
  • daf-16 protein, C elegans
  • Aquaporin 1
  • Receptor, IGF Type 1
  • Glucose
  • Glycerol

Associated data

  • GEO/GSE18563