Khrapko Konstantin, Vijg Jan
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
Trends Genet. 2009 Feb;25(2):91-8. doi: 10.1016/j.tig.2008.11.007. Epub 2008 Dec 26.
Although several lines of evidence support a role for accumulating somatic mitochondrial DNA (mtDNA) mutations in the etiology of aging, it remains unclear if they are a major cause of age-related deterioration and death. Mouse models that harbor elevated mtDNA mutation frequencies age prematurely; these findings were thought to provide conclusive evidence for a causal role of such mutations in aging. Yet, the presence of several conflicting reports has sparked controversy in the field and this is further aggravated by discrepancies in the estimates of mtDNA mutant fractions, which disagree by orders of magnitude. Here, we briefly review the evidence and some of the unresolved questions surrounding a causative role for accumulating mtDNA mutations in aging.
尽管有几条证据支持累积的体细胞线粒体DNA（mtDNA）突变在衰老病因学中发挥作用，但它们是否是与年龄相关的衰退和死亡的主要原因仍不清楚。携带升高的mtDNA突变频率的小鼠模型会过早衰老；这些发现被认为为此类突变在衰老中的因果作用提供了确凿证据。然而，几份相互矛盾的报告引发了该领域的争议，而mtDNA突变体比例估计值的差异使争议进一步加剧，这些估计值相差几个数量级。在这里，我们简要回顾一下围绕累积的mtDNA突变在衰老中的因果作用的证据以及一些尚未解决的问题。
