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

TitleGlucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression.
Publication TypeJournal Article
Year of Publication2009
AuthorsLee S-J, Murphy CT, Kenyon C
JournalCell Metab
Volume10
Issue5
Pagination379-91
Date Published2009 Nov
ISSN1932-7420
KeywordsAnimals, 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
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.

DOI10.1016/j.cmet.2009.10.003
Alternate JournalCell Metab.
PubMed ID19883616
PubMed Central IDPMC2887095
Grant ListR01 AG011816 / AG / NIA NIH HHS / United States
R37 AG011816 / AG / NIA NIH HHS / United States
R37 AG011816-16 / AG / NIA NIH HHS / United States
AG11816 / AG / NIA NIH HHS / United States