Analysis of mtDNA/nDNA Ratio in Mice

Quirós, Pedro M.; Goyal, Anish K.; Jha, Pooja; Auwerx, Johan

doi:10.1002/cpmo.21

Cited by 284 publications

(213 citation statements)

References 17 publications

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“…These data also add to the current understanding of PolG model in the context of aging more generally. Previous studies found that mtDNA copy number decreases with age [5,32]. Our results showed slightly decreased mtDNA copy number with age in wild-type mice, though it was not statistically significant.…”

Section: Copy Number Effectscontrasting

confidence: 80%

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

et al. 2020

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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, PolG D257A 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.

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Section: Copy Number Effectscontrasting

confidence: 80%

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

et al. 2020

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“…The copy number of mitochondrial gene ND1 was normalized to the single-copy nuclear gene. Relative mtDNA copy number was calculated and expressed by using the 2− ∆∆CT method [44].…”

Section: Quantification Of Mtdna Copy Numbermentioning

confidence: 99%

Multi-Tissue DNA Methylation Remodeling at Mitochondrial Quality Control Genes According to Diet in Rat Aging Models

et al. 2020

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An adequate mitochondrial quality control system ensures the maintenance of a healthy mitochondrial pool so as to slow down the progressive accumulation of damage affecting mitochondrial function during aging and diseases. The amount and quality of nutrients availability were demonstrated to induce a process of bioenergetics adaptation by influencing the above system via epigenetic modifications. Here, we analyzed DNA samples from differently-aged rats fed a standard or low-calorie diet to evaluate tissue-specific changes in DNA methylation of CpG sites falling within Polg, Polg2, Tfam, Fis1, and Opa1 genes. We found significant changes according to age and tissue type and the administration of the low-calorie diet is responsible for a prevalent increase in DNA methylation levels. Particularly, this increase was more appreciable when this diet was administered during adulthood and at old age. Regression analysis demonstrated that DNA methylation patterns of the analyzed genes were negatively correlated with their expression levels. Data we obtained provide the first evidence about changes in DNA methylation patterns of genes involved in the mitochondrial biogenesis in response to specific diets and demonstrated that epigenetic modifications are involved in the modulation of mitochondrial dynamics driven by age and nutrition.

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“…These data also add to the current understanding of PolG mice in particular. Previous studies found that mtDNA copy number decreases with age (5,30). Our results showed slightly decreased mtDNA copy number with age, though it was not statistically significant.…”

Section: Discussionmentioning

confidence: 93%

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

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Stebbings

Llano

et al. 2019

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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

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Analysis of mtDNA/nDNA Ratio in Mice

Cited by 284 publications

References 17 publications

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

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

Multi-Tissue DNA Methylation Remodeling at Mitochondrial Quality Control Genes According to Diet in Rat Aging Models

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

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