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bioRxiv · 10.1101/871426

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

Maclaine, K. D.·Stebbings, K. A.·Llano, D. A.·Rhodes, J. S.
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Abstract

The mitochondrial theory of aging attributes much of the aging process to mitochondrial DNA damage. The PolGAD257A/D257A (PolG) mutant mouse was created to explore the mitochondrial theory of aging and carries a mutated proofreading region of polymerase gamma, which exclusively transcribes the mitochondrial genome. As a result, PolG mice accumulate mitochondrial DNA (mtDNA) mutations which leads to premature aging including hair loss, weight loss, kyphosis, increased rates of apoptosis, organ damage, and eventually, an early death at around 12 months. Exercise has been reported to decrease skeletal muscle mtDNA mutations and normalize protein levels in PolG mice. However, brain mtDNA changes with exercise in PolG mice have not been explored. We found no effects of exercise on mtDNA mutations or copy number in brain or liver in PolG mice, despite effects on 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 mtDNA extraction and measuring mtDNA mutations to improve efficiency and accuracy.

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Maclaine, K. D., Stebbings, K. A., Llano, D. A., Rhodes, J. S.. 2019-12-10. Voluntary wheel running has no impact on brain and liver mitochondrial DNA copy number or mutation measures in the PolG mouse model of aging. https://doi.org/10.1101/871426

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