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

Abstract

32The mitochondrial theory of aging attributes much of the aging process to mitochondrial 33 DNA damage. The PolGA D257A/D257A (PolG) mutant mouse was created to explore the 34 mitochondrial theory of aging and carries a mutated proofreading region of polymerase 35 gamma, which exclusively transcribes the mitochondrial genome. As a result, PolG mice 36 accumulate mitochondrial DNA (mtDNA) mutations which leads to premature aging 37 including hair loss, weight loss, kyphosis, increased rates of apoptosis, organ damage, 38 and eventually, an early death at around 12 months. Exercise has been reported to 39 decrease skeletal muscle mtDNA mutations and normalize protein levels in PolG mice. 40 However, brain mtDNA changes with exercise in PolG mice have not been explored. 41 We found no effects of exercise on mtDNA mutations or copy number in brain or liver in 42 PolG mice, despite effects on body mass. Our results suggest that mitochondrial 43 mutations play little role in exercise-brain interactions in the PolG model of accelerated 44 aging. In addition to evaluating the effect of exercise on mtDNA outcomes, we also 45 implemented novel methods for mtDNA extraction and measuring mtDNA mutations to 46 improve efficiency and accuracy. 47 48 49 3 50