Metabolic shift from glycogen to trehalose promotes lifespan and healthspan in Caenorhabditis elegans
UMass Metabolic Network; Department of Molecular, Cell and Cancer Biology
Biochemical Phenomena, Metabolism, and Nutrition | Cell Biology | Cellular and Molecular Physiology | Nutritional and Metabolic Diseases
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.
daf-16, glycogen, gsy-1, lifespan, trehalose
DOI of Published Version
Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):E2791-E2800. doi: 10.1073/pnas.1714178115. Epub 2018 Mar 6. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Seo, Yonghak; Kingsley, Samuel F.; Walker, Griffin; Mondoux, Michelle A.; and Tissenbaum, Heidi A., "Metabolic shift from glycogen to trehalose promotes lifespan and healthspan in Caenorhabditis elegans" (2018). University of Massachusetts Medical School Faculty Publications. 1491.