Glucose Shortens the Life Span of C. elegans by Downregulating DAF-16/FOXO Activity and Aquaporin Gene Expression

Seung Jae Lee, Coleen T. Murphy, Cynthia Kenyon

Research output: Contribution to journalArticle

195 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)379-391
Number of pages13
JournalCell Metabolism
Volume10
Issue number5
DOIs
StatePublished - Nov 4 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

Keywords

  • HUMDISEASE

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