title: 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.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Coleen T
authors.initials: CT
authors.lastname: Murphy
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kenyon
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D025461:Feedback, Physiological; D051858:Forkhead Transcription Factors; D055786:Gene Knockout Techniques; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D007328:Insulin / Q000378:metabolism; D008136:Longevity; D017526:Receptor, IGF Type 1 / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D000076249:Heat Shock Transcription Factors; D007328:Insulin; D014157:Transcription Factors; C116823:aqp-1 protein, C elegans; C108831:daf-16 protein, C elegans; D051398:Aquaporin 1; D017526:Receptor, IGF Type 1; D005947:Glucose; D005990:Glycerol