Naked Mole-Rats Demonstrate Profound Tolerance to Low Oxygen, High Carbon Dioxide, and Chemical Pain

SIMPLE SUMMARY: Naked mole-rats live in crowded underground burrows where concentrations of oxygen can be low and concentrations of carbon dioxide can be high. Accordingly, this species is tolerant of low oxygen levels and high carbon dioxide levels, which would be deadly to most surface dwellers. The current article reviews what we know about these unusual tolerances and their underlying mechanisms. Understanding these mechanisms could lead to new strategies for treating human disorders related to low oxygen and high carbon dioxide, as experienced, for example, during a heart attack. ABSTRACT: Naked mole-rats (Heterocephalus glaber) are very unusual among subterranean mammals in that they live in large colonies and are extremely social, spending large amounts of time gathered together in underground nests more than a meter below the surface. Many respiring individuals resting in deep, poorly ventilated nests deplete the oxygen supply and increase the concentration of carbon dioxide. Consistent with living in that atmosphere, naked mole-rats tolerate levels of low oxygen and high carbon dioxide that are deadly to most surface-dwelling mammals. Naked mole-rats appear to have evolved a number of remarkable adaptations to be able to thrive in this harsh atmosphere. In order to successfully survive low oxygen atmospheres, they conserve energy utilization by reducing the physiological activity of all organs, manifest by reduced heart rate and brain activity. Amazingly, they resort to the anaerobic metabolism of fructose rather than glucose as a fuel to generate energy when challenged by anoxia. Similarly, high carbon dioxide atmospheres normally cause tissue acidosis, while naked mole-rats have a genetic mutation preventing both acid-induced pain and pulmonary edema. Together, these putative adaptations and the tolerances they provide make the naked mole-rat an important model for studying a host of biomedical challenges.