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.
Highlights
Heterocephalus glaber, the naked mole-rat (NMR), is a unique and fascinating mammal that has excited biologists since the discovery of its “insect-like” eusocial behavior [1]
While muscle wasting causes loss of bulk in many mammals during aging, we find that NMRs do not lose body mass in the first twenty years of life
In this report we demonstrate that NMRs show few signs of age-related muscle atrophy or mitochondrial dysfunction into old age
Summary
Heterocephalus glaber, the naked mole-rat (NMR), is a unique and fascinating mammal that has excited biologists since the discovery of its “insect-like” eusocial behavior [1]. While these animals have many unusual adaptations to their subterranean lifestyle, the discovery of their apparent resistance to cancer and exceptional longevity for a small rodent (over 30 years in captivity) has opened up new and important avenues of research [2]. The NMR is emerging as an exciting animal model for the study of aging These unique mammals exhibit negligible senescence, a phenomenon of very slow changes in the expected physiological characteristics with age, such as increased mortality and decreased physiological capacity [3]. While recent studies have reported that NMRs maintain vascular elasticity, cardiac function, gastrointestinal function, glucose tolerance, and reproductive capacity well into the third decade of life [5,6,7], no thorough investigation has been www.aging‐us.com undertaken regarding the status of skeletal muscle tissue in the aging naked mole-rat
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