Munro 2019 Aging Cell

From Bioblast
Publications in the MiPMap
Munro D, Baldy C, Pamenter ME, Treberg JR (2019) The exceptional longevity of the naked mole-rat may be explained by mitochondrial antioxidant defenses. Aging Cell 18:e12916.

Β» PMID: 30768748 Open Access

Munro D, Baldy C, Pamenter ME, Treberg JR (2019) Aging Cell

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 (H2O2; 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 H2O2 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.

Β© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. β€’ Keywords: Heterocephalus glaber, Antioxidants, Mitochondria, Reactive oxygen species, Skeletal muscle heart β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: CA Winnipeg Treberg JR

Labels: MiParea: Respiration, Comparative MiP;environmental MiP  Pathology: Aging;senescence  Stress:Oxidative stress;RONS  Organism: Mouse, Other mammals  Tissue;cell: Heart, Skeletal muscle  Preparation: Isolated mitochondria  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex IV;cytochrome c oxidase 

Coupling state: LEAK, OXPHOS  Pathway: N, S, NS  HRR: Oxygraph-2k, O2k-Fluorometer 

2019-02, AmR 

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