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Aging Cell. 2019 Jun;18(3):e12916. doi: 10.1111/acel.12916. Epub 2019 Feb 15.

The exceptional longevity of the naked mole-rat may be explained by mitochondrial antioxidant defenses.

Author information

1
Department of Biological Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
2
Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
3
Centre on Aging, University of Manitoba, Winnipeg, Manitoba, Canada.
4
University of Ottawa Brain and Mind Research Institute, Ottawa, Ontario, Canada.
5
Department of food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

Abstract

Naked mole-rats (NMRs) are mouse-sized mammals that exhibit an exceptionally long lifespan (>30 vs. <4 years for mice), and resist aging-related pathologies such as cardiovascular and pulmonary diseases, cancer, and neurodegeneration. However, the mechanisms underlying this exceptional longevity and disease resistance remain poorly understood. The oxidative stress theory of aging posits that (a) senescence results from the accumulation of oxidative damage inflicted by reactive oxygen species (ROS) of mitochondrial origin, and (b) mitochondria of long-lived species produce less ROS than do mitochondria of short-lived species. However, comparative studies over the past 28 years have produced equivocal results supporting this latter prediction. We hypothesized that, rather than differences in ROS generation, the capacity of mitochondria to consume ROS might distinguish long-lived species from short-lived species. To test this hypothesis, we compared mitochondrial production and consumption of hydrogen peroxide (H2 O2 ; as a proxy of overall ROS metabolism) between NMR and mouse skeletal muscle and heart. We found that the two species had comparable rates of mitochondrial H2 O2 generation in both tissues; however, the capacity of mitochondria to consume ROS was markedly greater in NMRs. Specifically, maximal observed consumption rates were approximately two and fivefold greater in NMRs than in mice, for skeletal muscle and heart, respectively. Our results indicate that differences in matrix ROS detoxification capacity between species may contribute to their divergence in lifespan.

KEYWORDS:

Heterocephalus glaber ; antioxidants; mitochondria; reactive oxygen species; skeletal muscle heart

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