Glucose Shortens the Life Span of C. elegans by Downregulating DAF-16/FOXO Activity and Aquaporin Gene Expression

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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.
Publisher
CELL PRESS
Issue Date
2009-11
Language
English
Article Type
Article
Citation

CELL METABOLISM, v.10, no.5, pp.379 - 391

ISSN
1550-4131
DOI
10.1016/j.cmet.2009.10.003
URI
http://hdl.handle.net/10203/251727
Appears in Collection
BS-Journal Papers(저널논문)
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