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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.

SUBMITTER: Lee SJ 

PROVIDER: S-EPMC2887095 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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

Lee Seung-Jae SJ   Murphy Coleen T CT   Kenyon Cynthia C  

Cell metabolism 20091101 5


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  ...[more]

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