Oxygen is Toxic in the Cold in C. elegans.

Temperature and oxygen are two factors that profoundly affect survival limits of animals; too much or too little of either is lethal. However, both humans and animals can exhibit exceptional survival when oxygen and temperature are simultaneously low. To better understand this apparent synergistic interaction between oxygen and temperature, we assayed the survival of Caenorhabditis elegans in experimental environments at different temperatures and oxygen concentrations. While nematodes cannot survive a day in room air at 2 {degrees}C (cold shock), we found that when oxygen is low, 200-fold less than room air, they can survive this temperature for 48 hours. Consistent with this, we found that worms exposed to high oxygen concentrations, 35 times greater than room air, are more sensitive to low temperature than worms in room air. These results show that normal atmospheric levels of oxygen are toxic in the cold. Using these survival assays, we found that cold acclimatization protects worms from lethal effects of high oxygen, mutations in the cold acclimatization pathway affect oxygen tolerance, and that the naturally occurring and physiologically relevant compounds glucose, manganese (II), and ascorbate improve survival limits in both low temperature and high oxygen when supplied early in life. These results show that the interdependence of temperature and oxygen on survival in C. elegans is based in part on shared physiological mechanisms involved in response to these two environmental stressors. The evolution and natural history of stress responses in animals suggest similar phenomena may function in humans.