Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression. Author Seung-Jae Lee, Coleen Murphy, Cynthia Kenyon Publication Year 2009 Type Journal Article 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. Keywords Animals, Gene Knockout Techniques, Signal Transduction, Glucose, Down-Regulation, Transcription Factors, DNA-Binding Proteins, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Feedback, Physiological, Insulin, Longevity, Receptor, IGF Type 1, Aquaporin 1, Glycerol Journal Cell Metab Volume 10 Issue 5 Pages 379-91 Date Published 11/2009 Alternate Journal Cell Metab. Google ScholarBibTeXEndNote X3 XML