@article{2045, 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}, author = {Seung-Jae Lee and Coleen Murphy and Cynthia Kenyon}, title = {Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression.}, 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.

}, year = {2009}, journal = {Cell Metab}, volume = {10}, pages = {379-91}, month = {11/2009}, language = {eng}, }