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African Naked Mole-Rats Demonstrate Extreme Tolerance to Hypoxia and Hypercapnia

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The Extraordinary Biology of the Naked Mole-Rat

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1319))

Abstract

Naked mole-rats are extremely tolerant to low concentrations of oxygen (hypoxia) and high concentrations of carbon dioxide (hypercapnia), which is consistent with the environment that they inhabit. Naked mole-rats combine subterranean living with living in very densely populated colonies where oxygen becomes depleted and carbon dioxide accumulates. In the laboratory, naked mole-rats fully recover from 5 h exposure to 5% O2 and 5 h exposure to 80% CO2, whereas both conditions are rapidly lethal to similarly sized laboratory mice. During anoxia (0% O2) naked mole-rats enter a suspended animation-like state and switch from aerobic metabolism of glucose to anaerobic metabolism of fructose. Additional fascinating characteristics include that naked mole-rats show intrinsic brain tolerance to anoxia; a complete lack of hypoxia-induced and CO2-induced pulmonary edema; and reduced aversion to high concentrations of CO2 and acidic fumes. Here we outline a constellation of physiological and molecular adaptations that correlate with the naked mole-rat’s hypoxic/hypercapnic tolerance and which offer potential targets for ameliorating pathological conditions in humans, such as the damage caused during cerebral ischemia.

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Photo Credit: Thomas Park

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Acknowledgements

We are grateful for the extremely helpful suggestions of two reviewers. We are also grateful for grant support from the National Science Foundation (grant number 0744979 to TJP), a Cancer Research UK/RCUK Multidisciplinary Project Award (C56829/A22053 to ESJS) and ERC advanced grants (AdG 789128 and AdG 294678 to GRL).

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Authors and Affiliations

  1. Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA

    Thomas J. Park & Daniel T. Applegate

  2. Department of Pharmacology, University of Cambridge, Cambridge, UK

    Ewan St. J. Smith

  3. Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany

    Jane Reznick

  4. Mammal Research Institute, Department of Zoology and Entomology, University of Pretoria, Pretoria, South Africa

    N. C. Bennett

  5. Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA

    John Larson

  6. Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Berlin, Germany

    Gary R. Lewin

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  1. Thomas J. Park
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Correspondence to Thomas J. Park .

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Editors and Affiliations

  1. Calico Life Sciences LLC, South San Francisco, CA, USA

    Rochelle Buffenstein

  2. Laboratory of Integrative NeuroscienceDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA

    Thomas J. Park

  3. Department of Psychology, University of Toronto Mississauga, Mississauga, ON, Canada

    Melissa M. Holmes

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Park, T.J. et al. (2021). African Naked Mole-Rats Demonstrate Extreme Tolerance to Hypoxia and Hypercapnia. In: Buffenstein, R., Park, T.J., Holmes, M.M. (eds) The Extraordinary Biology of the Naked Mole-Rat. Advances in Experimental Medicine and Biology, vol 1319. Springer, Cham. https://doi.org/10.1007/978-3-030-65943-1_9

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