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Naked mole-rats maintain healthy skeletal muscle and Complex IV mitochondrial enzyme function into old age

Lookup NU author(s): Dr Elizabeth Stoll, Nevena Karapavlovic, Hannah Rosa, Michael Woodmass, Dr Karolina Rygiel, Dr Kathryn White, Emeritus Professor Doug Turnbull

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

The naked mole-rat (NMR) Heterocephalus glaber is an exceptionally long-lived rodent, living up to 32 years in captivity. This extended lifespan is accompanied by a phenotype of negligible senescence, a phenomenon of very slow changes in the expected physiological characteristics with age. One of the many consequences of normal aging in mammals is the devastating and progressive loss of skeletal muscle, termed sarcopenia, caused in part by respiratory enzyme dysfunction within the mitochondria of skeletal muscle fibers. Here we report that NMRs avoid sarcopenia for decades. Muscle fiber integrity and mitochondrial ultrastructure are largely maintained in aged animals. While mitochondrial Complex IV expression and activity remains stable, Complex I expression is significantly decreased. We show that aged naked mole-rat skeletal muscle tissue contains some mitochondrial DNA rearrangements, although the common mitochondrial DNA deletions associated with aging in human and other rodent skeletal muscles are not present. Interestingly, NMR skeletal muscle fibers demonstrate a significant increase in mitochondrial DNA copy number. These results have intriguing implications for the role of mitochondria in aging, suggesting Complex IV, but not Complex I, function is maintained in the long-lived naked mole rat, where sarcopenia is avoided and healthy muscle function is maintained for decades.


Publication metadata

Author(s): Stoll EA, Karapavlovic N, Rosa H, Woodmass M, Rygiel K, White K, Turnbull DM, Faulkes CG

Publication type: Article

Publication status: Published

Journal: Aging (Albany)

Year: 2016

Volume: 8

Issue: 12

Pages: 3468–3483

Online publication date: 19/12/2016

Acceptance date: 05/12/2016

Date deposited: 05/02/2017

ISSN (electronic): 1945-4589

Publisher: Impact Journals LLC

URL: http://dx.doi.org/10.18632/aging.101140

DOI: 10.18632/aging.101140


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Funding

Funder referenceFunder name
Newcastle University Centre for Brain Ageing and Vitality (Biotechnology and Biological Sciences Research Council)
Newcastle University Centre for Brain Ageing and Vitality (Economic and Social Research Council)
Newcastle University Centre for Brain Ageing and Vitality (Engineering and Physical Sciences Research Council)
UK NIHR Biomedical Research Centre in Age
096919/Z/11/ZWellcome Trust Centre for Mitochondrial Research
G000608-1MRC Centre for Neuromuscular Disease
G0700718Newcastle University Centre for Brain Ageing and Vitality (Medical Research Council)

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