Authors: Lee SJ; Murphy CT; Kenyon C
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; Aquaporin 1/antagonists & inhibitors/genetics/*metabolism; Caenorhabditis elegans/*physiology; Caenorhabditis elegans Proteins/antagonists & inhibitors/genetics/*metabolism; DNA-Binding Proteins/antagonists & inhibitors/genetics/*metabolism; Down-Regulation; Feedback, Physiological; Gene Knockout Techniques; Glucose/*metabolism; Glycerol/metabolism; Insulin/metabolism; Longevity; Receptor, IGF Type 1/physiology; *Signal Transduction; Transcription Factors/antagonists & inhibitors/genetics/*metabolism
Journal: Cell metabolism
Date: Nov. 4, 2009
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Lee SJ, Murphy CT, Kenyon C (2009) Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression. Cell metabolism 10: 379-91.