The proliferation of mitochondrial DNA (mtDNA) with deletion mutations has been linked to aging and age related neurodegenerative conditions. In this study we model the effect of mtDNA half-life on mtDNA competition and selection. It has been proposed that mutation deletions (\(\text {mtDNA}_{del}\)) have a replicative advantage over wild-type (\(\text {mtDNA}_{wild}\)) and that this is detrimental to the host cell, especially in post-mitotic cells. An individual cell can be viewed as forming a closed ecosystem containing a large population of independently replicating mtDNA. Within this enclosed environment a selfishly replicating \(\text {mtDNA}_{del}\) would compete with the \(\text {mtDNA}_{wild}\) for space and resources to the detriment of the host cell. In this paper, we use a computer simulation to model cell survival in an environment where \(\text {mtDNA}_{wild}\) compete with \(\text {mtDNA}_{del}\) such that the cell expires upon \(\text {mtDNA}_{wild}\) extinction. We focus on the survival time for long lived post-mitotic cells, such as neurons. We confirm previous observations that \(\text {mtDNA}_{del}\) do have a replicative advantage over \(\text {mtDNA}_{wild}\). As expected, cell survival times diminished with increased mutation probabilities, however, the relationship between survival time and mutation rate was non-linear, that is, a ten-fold increase in mutation probability only halved the survival time. The results of our model also showed that a modest increase in half-life had a profound affect on extending cell survival time, thereby, mitigating the replicative advantage of \(\text {mtDNA}_{del}\). Given the relevance of mitochondrial dysfunction to various neurodegenerative conditions, we propose that therapies to increase mtDNA half-life could significantly delay their onset.

具有缺失突变的线粒体 DNA (mtDNA) 的增殖与衰老和与年龄相关的神经退行性疾病有关。在这项研究中，我们模拟了 mtDNA 半衰期对 mtDNA 竞争和选择的影响。有人提出突变缺失（\(\text {mtDNA}_{del}\)）比野生型（\(\text {mtDNA}_{wild}\)）具有复制优势，这是有害的到宿主细胞，特别是在有丝分裂后的细胞中。单个细胞可以被视为形成一个封闭的生态系统，其中包含大量独立复制的 mtDNA。在这个封闭的环境中，一个自私复制的\(\text {mtDNA}_{del}\)将与\(\text {mtDNA}_{wild}\)空间和资源，从而损害宿主细胞。在本文中，我们使用计算机模拟来模拟在\(\text {mtDNA}_{wild}\)与\(\text {mtDNA}_{del}\)竞争使得细胞到期的环境中的细胞存活在\(\text {mtDNA}_{wild}\)灭绝后。我们专注于长寿命的有丝分裂后细胞（如神经元）的存活时间。我们证实了之前的观察结果，即\(\text {mtDNA}_{del}\)确实比\(\text {mtDNA}_{wild}\)具有复制优势. 正如预期的那样，细胞存活时间随着突变概率的增加而减少，然而，存活时间和突变率之间的关系是非线性的，即突变概率增加十倍只会使存活时间减半。我们模型的结果还表明，半衰期的适度增加对延长细胞存活时间有深远的影响，从而减轻了\(\text {mtDNA}_{del}\)的复制优势。鉴于线粒体功能障碍与各种神经退行性疾病的相关性，我们建议增加 mtDNA 半衰期的疗法可以显着延迟其发作。