Rethinking the mitochondrial theory of aging - The role of mitochondrial gene expression in lifespan determination
Rethinking the mitochondrial theory of aging - The role of mitochondrial gene expression in lifespan determination
复制标题
DOI：
10.4161/cc.6.13.4457
复制
发表时间：
2007-07-01
期刊：
影响因子：
4.3
通讯作者：
Shadel, Gerald S.
中科院分区：
文献类型：
--
作者：
Bonawitz, Nicholas D.;Shadel, Gerald S.
线粒体衰老理论假设mtDNA突变和线粒体功能障碍的积累是产生衰老表型和限制寿命的原因。尽管这一理论被广泛接受，但仍未得到证实，因为支持它的证据虽然大量，但在很大程度上是相互关联的。此外，最近在小鼠中进行的mtDNA突变速率加快的实验结果对线粒体理论的传统表述提出了挑战，可能需要对其一些核心原则进行重新评估。从这个角度来看，我们总结了最近的研究表明，线粒体基因表达的数量和质量在衰老过程中发挥的作用比以前认识到的要大得多。我们推测这种形式的线粒体功能障碍可能独立或与mtDNA突变协同作用，从而促进与年龄相关的病理和限制寿命。
The Mitochondrial Theory of Aging postulates that accumulation of mtDNA mutations and mitochondrial dysfunction are responsible for generating aging phenotypes and limiting lifespan. Although widely accepted, this theory remains unproven because the evidence supporting it, while substantial, is largely correlative. Furthermore, recent exper imental results in mice with accelerated rates of mtDNA mutagenesis have challenged the traditional formulation of the Mitochondrial Theory, perhaps warranting a reevaluation of some of its core principles. In this perspective, we summarize recent work suggesting that both the quantity and the quality of mitochondrial gene expression play a much greater role in the aging process than previously appreciated. We speculate that this form of mitochondrial dysfunction may operate independently or in concert with mtDNA mutations to promote age - related pathology and limit lifespan.