Title | Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Lee, S-J, Murphy, CT, Kenyon, C |
Journal | Cell Metab |
Volume | 10 |
Issue | 5 |
Pagination | 379-91 |
Date Published | 2009 Nov |
Keywords | Animals, Aquaporin 1, Caenorhabditis elegans, Caenorhabditis elegans Proteins, DNA-Binding Proteins, Down-Regulation, Feedback, Physiological, Gene Knockout Techniques, Glucose, Glycerol, Insulin, Longevity, Receptor, IGF Type 1, Signal Transduction, Transcription Factors |
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. |
Alternate Journal | Cell Metab. |