Reference - Detail
| RRC ID | 6390 |
|---|---|
| Author | Lee SJ, Murphy CT, Kenyon C. |
| Title | Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression. |
| Journal | Cell Metab |
| 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. |
| Volume | 10(5) |
| Pages | 379-91 |
| Published | 2009-11-1 |
| DOI | 10.1016/j.cmet.2009.10.003 |
| PII | S1550-4131(09)00302-7 |
| PMID | 19883616 |
| PMC | PMC2887095 |
| MeSH | Animals Aquaporin 1 / antagonists & inhibitors Aquaporin 1 / genetics Aquaporin 1 / metabolism* Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / antagonists & inhibitors Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA-Binding Proteins / antagonists & inhibitors DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Down-Regulation Feedback, Physiological Forkhead Transcription Factors Gene Knockout Techniques Glucose / metabolism* Glycerol / metabolism Heat Shock Transcription Factors Insulin / metabolism Longevity Receptor, IGF Type 1 / physiology Signal Transduction* Transcription Factors / antagonists & inhibitors Transcription Factors / genetics Transcription Factors / metabolism* |
| IF | 21.567 |
| Times Cited | 185 |
| WOS Category | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
| Resource | |
| C.elegans | tm339 |