A Spoonful of Sugar Makes Life Span Go Down (2009.11.4)
Many studies have addressed the effect of sugar in the diet on obesity and diabetes. Professor Seung-Jae Lee (Division of IT Convergence Engineering, Department of Life Science, School of Interdisciplinary Bioscience and Bioengineering) and his group report that it might also be taking years off the life span.
Professor Lee’s group, in collaboration with Professor Cynthia Kenyon of the University of California, San Francisco, discovered that glucose inhibits the activities of the glycerol channel in C. elegans, shortening the life span of the worm by about 20 percent. The group traces the effect to insulin signals, which can block other life-extending molecular players.
Insulin reduces similar glycerol channels in mammals, suggesting that this glucose-responsive pathway might be conserved evolutionarily. The findings raise the possibility that a low-sugar diet might have beneficial effects on life span in higher organisms.
The research group discovered in the early 90s that mutations that effected insulin signals could double the normal life span of worms. Specifically, a mutation in a gene known as daf-2 slowed aging and doubled life span. That longer life needed other genes called the FOXO transcription factor DAF-16 and the heat shock factor HSF-1.
Now, the researchers show that those same genes are also involved in numbering the days of worms which are fed on glucose. In fact, glucose makes no difference to the life span of worms that lack DAF-16 or HSF-1, they show. Glucose also completely prevents the life-extending benefits that would otherwise come with mutations in the daf-2 gene.
Ultimately, worms fed a steady diet containing glucose show a reduction in aquaporin channels that transport glycerol, one of the ingredients in the process by which the body produces its own glucose: if there is not enough glucose, the body makes it with glycerol. That glycerol has to first get where it needs to go, which it does via the aquaporin channels.
Further studies are needed to see if these same effects of sugar can be seen in mice, or even people. But there is reason to think they may. “Although the mechanism by which glucose shortens the life span of C. elegans is not yet fully understood, the fact that the two mammalian aquaporin glycerol-transporting channels are downregulated by insulin raises the possibility that glucose may have a life-span-shortening effect in humans, and, conversely, that a diet with a low glycemic index may extend human life span,” the researchers wrote.
The findings may also have implications for drugs in development for the treatment of diabetes, which are meant to block glucose production by inhibiting glycerol channels. The new findings suggest that glycerol channels might be doing something else, and that drugs designed to block them might have a downside.
The results of the study were introduced under the title, “Glucose Shortens the Life Span of C. elegans by Downregulating DAF-16/FOXO Activity and Aquaporin Gene Expression” in the November 4, 2009, issue of Cell Metabolism, Volume 10, Issue 5, Pages 379-391.