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The Idiosyncratic Physiological Traits of the Naked Mole-Rat; a Resilient Animal Model of Aging, Longevity, and Healthspan

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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

The subterranean-dwelling naked mole-rat (Heterocephalus glaber) is an extremophilic rodent, able to thrive in the harsh underground conditions of sub-Saharan Northeast Africa. This pelage-free mammal exhibits numerous unusual ecophysiological features including pronounced tolerance of thermolability, hypoxia, hypercapnia and noxious substances. As a mammal, the naked mole-rat provides a proof-of-concept that age-related changes in physiology are avoidable. At ages far beyond their expected lifespans given both their body size and/or the timing of early developmental milestones, naked mole-rats fail to exhibit meaningful changes in physiological health or demographic mortality. Lack of physiological deterioration with age is also evident in lean and fat mass, bone quality, and reproductive capacity. Rather, regardless of age, under basal conditions naked mole-rats appear to “idle on low” with their “shields up” as is manifested by low body temperature, metabolic rate, cardiac output and kidney concentrating ability, enabling better protection of organs and cellular function. When needed, they can nevertheless ramp up these functions, increasing cardiac output and metabolism 2–5 fold. Here we review many unusual aspects of their physiology and examine how these attributes facilitate both tolerance of the diverse suite of hostile conditions encountered in their natural milieu as well as contribute to their extraordinary longevity and resistance to common, age-related chronic diseases.

figure a

Thirty seven year-old naked mole-rat (Photo Credit: Ben Passarelli)

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Acknowledgements

We thank David Botstein, Graham Ruby and anonymous reviewers for their constructive critique of this chapter. Financial support from Calico Life Sciences LLC is gratefully acknowledged. Figures were created using Biorender.com

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    Rochelle Buffenstein & Wendy Craft

  2. Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX, USA

    Rochelle Buffenstein

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Correspondence to Rochelle Buffenstein .

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    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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Buffenstein, R., Craft, W. (2021). The Idiosyncratic Physiological Traits of the Naked Mole-Rat; a Resilient Animal Model of Aging, Longevity, and Healthspan. 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_8

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