Voluntary wheel running has no impact on brain and liver mitochondrial DNA copy number or mutation measures in the PolG mouse model of aging

• Published in: PloS one Vol. 15; no. 3; p. e0226860
• Main Authors: Maclaine, Kendra D, Stebbings, Kevin A, Llano, Daniel A, Rhodes, Justin S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02-03-2020; Public Library of Science (PLoS)
• Subjects: Accuracy; Age; Aging; Aging, Premature - genetics; Aging, Premature - pathology; Aging, Premature - physiopathology; Aging, Premature - prevention & control; Alopecia; Analysis; Animals; Apoptosis; Biology and life sciences; Body mass; Body weight loss; Brain; Brain - cytology; Brain - metabolism; Brain - pathology; Brain research; Copy number; Damage; Death; Deoxyribonucleic acid; Disease Models, Animal; DNA; DNA Copy Number Variations; DNA damage; DNA Damage - physiology; DNA Polymerase gamma - genetics; DNA Polymerase gamma - metabolism; DNA, Mitochondrial - genetics; DNA, Mitochondrial - isolation & purification; DNA, Mitochondrial - metabolism; Evaluation; Genetic aspects; Genomes; Genomics; Hair loss; Humans; Kyphosis; Liver; Liver - cytology; Liver - metabolism; Liver - pathology; Male; Measurement; Medicine and Health Sciences; Metabolism; Mice; Mice, Transgenic; Mitochondrial DNA; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscles; Musculoskeletal system; Mutants; Mutation; Neurosciences; Novels; Physical Conditioning, Animal - physiology; Physical training; Proofreading; Research and Analysis Methods; Skeletal muscle; Studies; Weight loss; Wheel running; United States > US; Illinois
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0226860

The mitochondrial theory of aging attributes much of the aging process to mitochondrial DNA damage. The polymerase gamma (PolG) mutant mouse was designed to evaluate this theory and thus carries a mutated proofreading region of polymerase gamma (D257A) that exclusively transcribes the mitochondrial genome. As a result, PolGD257A mice accumulate mitochondrial DNA (mtDNA) mutations that lead to premature aging, as evidenced by hair loss, weight loss, kyphosis, increased rates of apoptosis, organ damage, and an early death, occurring around 12 months of age. Research has shown that exercise decreases skeletal muscle mtDNA mutations and normalizes protein levels in PolG mice. However, brain mtDNA changes with exercise in PolG mice have not been studied. We found no effects of exercise on mtDNA mutations or copy number in either the brain or liver of PolG mice, despite changes to body mass. Our results suggest that mitochondrial mutations play little role in exercise-brain interactions in the PolG model of accelerated aging. In addition to evaluating the effect of exercise on mtDNA outcomes, we also implemented novel methods for both extracting mtDNA and measuring mtDNA mutations, with aims for improving the efficiency and accuracy of these methods.