|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|
|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|
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.|