Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression

Author: Lee, S.-J., Murphy, C. T., & Kenyon, C.

Description: 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.

Subject headings: Animals; Aquaporin 1; Caenorhabditis elegans; Caenorhabditis elegans Proteins; DNA-Binding Proteins; Down-Regulation; Feedback; Physiological; Forkhead Transcription Factors; Gene Knockout Techniques; Glucose; Glycerol; Heat Shock Transcription Factors; Insulin; Longevity; Receptor; IGF Type 1; Signal Transduction; Transcription Factors

Publication year: 2009

Journal or book title: Cell Metabolism

Volume: 10

Issue: 5

Pages: 379–391

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Type: Journal article

Serial number: 3146

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