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Definition: Why is mitochondrial DNA repair capacity reduced with age?

Mitochondrial DNA (mtDNA) repair capacity refers to the ability of cells to correct damage or mutations in the mitochondrial DNA. As individuals age, there is a gradual decline in the efficiency of mtDNA repair mechanisms, leading to an accumulation of DNA damage in the mitochondria.

Causes of reduced mitochondrial DNA repair capacity with age:

1. Oxidative stress: Mitochondria are the primary source of reactive oxygen species (ROS) in cells. Over time, the production of ROS increases, leading to oxidative damage to mtDNA. This oxidative stress can overwhelm the repair mechanisms, resulting in reduced repair capacity.

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2. Decline in repair enzymes: The activity of enzymes involved in mtDNA repair, such as DNA polymerases and exonucleases, decreases with age. This decline in enzyme function impairs the repair process and contributes to reduced repair capacity.

3. Accumulation of mtDNA mutations: As mtDNA repair capacity declines, the accumulation of mutations in the mitochondrial genome increases. These mutations can disrupt mitochondrial function and contribute to age-related decline in cellular and tissue function.

4. Mitochondrial dynamics: Mitochondria undergo constant fusion and fission processes, which play a crucial role in maintaining mtDNA integrity. With age, there is a decline in mitochondrial dynamics, leading to impaired mtDNA repair and increased susceptibility to damage.

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5. Epigenetic changes: Epigenetic modifications, such as DNA methylation and histone modifications, can affect the expression of genes involved in mtDNA repair. Age-related changes in epigenetic patterns can lead to altered repair capacity and increased vulnerability to mtDNA damage.

6. Energy imbalance: Mitochondria are responsible for energy production through oxidative phosphorylation. Age-related decline in mitochondrial function and energy production can compromise the availability of ATP, which is essential for DNA repair processes.

Understanding the factors contributing to reduced mtDNA repair capacity with age is crucial for developing interventions to mitigate the accumulation of mtDNA damage and potentially extend healthy lifespan.

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Keywords: repair, mitochondrial, capacity, damage, decline, reduced, mutations, accumulation, mitochondria