RRC ID 53944
著者 Seo Y, Kingsley S, Walker G, Mondoux MA, Tissenbaum HA.
タイトル Metabolic shift from glycogen to trehalose promotes lifespan and healthspan in Caenorhabditis elegans.
ジャーナル Proc Natl Acad Sci U S A
Abstract As Western diets continue to include an ever-increasing amount of sugar, there has been a rise in obesity and type 2 diabetes. To avoid metabolic diseases, the body must maintain proper metabolism, even on a high-sugar diet. In both humans and Caenorhabditis elegans, excess sugar (glucose) is stored as glycogen. Here, we find that animals increased stored glycogen as they aged, whereas even young adult animals had increased stored glycogen on a high-sugar diet. Decreasing the amount of glycogen storage by modulating the C. elegans glycogen synthase, gsy-1, a key enzyme in glycogen synthesis, can extend lifespan, prolong healthspan, and limit the detrimental effects of a high-sugar diet. Importantly, limiting glycogen storage leads to a metabolic shift whereby glucose is now stored as trehalose. Two additional means to increase trehalose show similar longevity extension. Increased trehalose is entirely dependent on a functional FOXO transcription factor DAF-16 and autophagy to promote lifespan and healthspan extension. Our results reveal that when glucose is stored as glycogen, it is detrimental, whereas, when stored as trehalose, animals live a longer, healthier life if DAF-16 is functional. Taken together, these results demonstrate that trehalose modulation may be an avenue for combatting high-sugar-diet pathology.
巻・号 115(12)
ページ E2791-E2800
公開日 2018-3-20
DOI 10.1073/pnas.1714178115
PII 1714178115
PMID 29511104
PMC PMC5866546
MeSH Animals Animals, Genetically Modified Autophagy / physiology Caenorhabditis elegans / drug effects Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism Glucose / metabolism Glucose / toxicity Glycogen / genetics Glycogen / metabolism* Longevity Time Factors Trehalose / genetics Trehalose / metabolism*
IF 9.412
引用数 21
リソース情報
線虫 tm6196