title: Naked mole-rats maintain healthy skeletal muscle and Complex IV mitochondrial enzyme function into old age.
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.
authors.affiliation: LLHW Centre for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.|Wellcome Trust Centre for Mitochondrial Research, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.|Institute for Neuroscience, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Stoll
authors.affiliation: Undergraduate Programme in Biomedical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Nevena
authors.initials: N
authors.lastname: Karapavlovic
authors.affiliation: LLHW Centre for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.|Wellcome Trust Centre for Mitochondrial Research, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.|Institute for Neuroscience, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Hannah
authors.initials: H
authors.lastname: Rosa
authors.affiliation: Undergraduate Programme in Biomedical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Woodmass
authors.affiliation: LLHW Centre for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.|Wellcome Trust Centre for Mitochondrial Research, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.|Institute for Neuroscience, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Karolina
authors.initials: K
authors.lastname: Rygiel
authors.affiliation: Electron Microscopy Research Services, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Kathryn
authors.initials: K
authors.lastname: White
authors.affiliation: LLHW Centre for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.|Wellcome Trust Centre for Mitochondrial Research, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.|Institute for Neuroscience, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Douglass M
authors.initials: DM
authors.lastname: Turnbull
authors.affiliation: School of Biological & Chemical Sciences, Queen Mary University of London, London, E1 4NS, UK.
authors.forename: Chris G
authors.initials: CG
authors.lastname: Faulkes
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D042967:Electron Transport Complex I / Q000502:physiology; D003576:Electron Transport Complex IV / Q000502:physiology*; D008297:Male; D019577:Mole Rats; D018482:Muscle, Skeletal / Q000502:physiology*; D009133:Muscular Atrophy
chemical_list: D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I
keywords: animal models of aging; mitochondria; naked mole-rat; oxidative stress; sarcopenia