Metabolic shift from glycogen to trehalose promotes lifespan and healthspan in Caenorhabditis elegans
| Autor: | Samuel F. Kingsley, Heidi A. Tissenbaum, Yong-Hak Seo, Griffin Patrick Walker, Michelle A. Mondoux |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Multidisciplinary biology Glycogen media_common.quotation_subject Autophagy Longevity Metabolism biology.organism_classification Trehalose Cell biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry Daf-16 biology.protein Glycogen synthase Caenorhabditis elegans media_common |
| Zdroj: | Proceedings of the National Academy of Sciences. 115 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1714178115 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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