RRC ID 6390
著者 Lee SJ, Murphy CT, Kenyon C.
タイトル Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression.
ジャーナル 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.
巻・号 10(5)
ページ 379-91
公開日 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
引用数 185
WOS 分野 ENDOCRINOLOGY & METABOLISM CELL BIOLOGY
リソース情報
線虫 tm339