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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aquaporin 1 / antagonists & inhibitors
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Aquaporin 1 / genetics
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Aquaporin 1 / metabolism*
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins / antagonists & inhibitors
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Down-Regulation
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Feedback, Physiological
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Forkhead Transcription Factors
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Gene Knockout Techniques
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Glucose / metabolism*
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Glycerol / metabolism
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Heat Shock Transcription Factors
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Insulin / metabolism
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Longevity
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Receptor, IGF Type 1 / physiology
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Signal Transduction*
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Caenorhabditis elegans Proteins
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DNA-Binding Proteins
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Forkhead Transcription Factors
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Heat Shock Transcription Factors
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Insulin
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Transcription Factors
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aqp-1 protein, C elegans
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daf-16 protein, C elegans
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Aquaporin 1
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Receptor, IGF Type 1
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Glucose
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Glycerol