Diet and Environment Influence Oxygen-Deprivation Survival in C. elegans

Oxygen deprivation plays a central role in the pathology of a number of human diseases including stroke, 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 the association between environment and oxygen deprivation responses. C. elegans is particularly well suited for this work given that it is a genetic and cellular model system and has the ability to survive severe oxygen deprivation (anoxia). Additionally, others and our studies have shown that diet and environment affect anoxia survival rate and lifespan. We hypothesize that added dietary sugar (glucose or fructose) will affect anoxia response and survival in C. elegans, and that this response can be modulated genetically. We determined that wild-type animals fed glucose had a significant decrease in anoxia survival rate. Methodologies are being used to determine if the glucose-induced anoxia sensitivity observed in wild-type animals is due to direct and/or indirect effects. The glucose-fed anoxia phenotype is suppressed by mutations in genes involved with highly conserved pathways including insulin-like signaling (daf-16) and O-GlcNAc post-translational modification (PTM) of proteins (oga-1), suggesting that carbohydrate metabolism and PTMs have a role in oxygen-deprivation survival. This work will provide a greater understanding of the association between diet, environment, genetics and oxygen deprivation responses; this is relevant to human health related issues including cardiac dysfunction and diabetes.