Dietary Carbohydrates Affect Oxygen-Deprivation Survival in C.elegans

Oxygen deprivation plays a central role in the pathology of a number of human diseases including stroke, pulmonary and cardiac dysfunction and solid tumor cell progression. Progression of these diseases is influenced by diet, environment and genetics. Consequently, there is interest in understanding the relationship between environment, genotype and the survival of oxygen deprivation. We are using the genetic model system Caenorhabditis elegans to study oxygen deprivation. C. elegans, a soil nematode, has the ability to survive severe oxygen deprivation (anoxia). Others and our previous studies have shown that food source affects anoxia survival and adult lifespan. The insulin-like signaling pathway, which is highly conserved between nematodes and mammals, is known to have a role in lifespan and stress responses.

We hypothesize that carbohydrates in the diet will influence anoxia survival in C. elegans. We determined that the addition of low levels of dietary glucose (2%) significantly decreased anoxia survival rate. This phenotype is suppressed by mutations in genes involved with the insulin-signaling pathway or post-translational modifications of glycoproteins. Furthermore, the glucose-induced sensitivity to anoxia phenotype is suppressed by the addition of metformin to the diet; metformin is a drug used to treat diabetes and modulates the AMPK and insulin-signaling pathway.

Together these data suggest that carbohydrate metabolism plays a crucial role in survival of oxygen deprivation and that C. elegans is a well-suited genetic model system to study glucose toxicity. This work is significant given the central role diet and oxygen deprivation has on human health related issues.