Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany.
J Clin Invest. 2013 Mar;123(3):951-7. doi: 10.1172/JCI64125. Epub 2013 Mar 1.
Over the last decade, accumulating evidence has suggested a causative link between mitochondrial dysfunction and major phenotypes associated with aging. Somatic mitochondrial DNA (mtDNA) mutations and respiratory chain dysfunction accompany normal aging, but the first direct experimental evidence that increased mtDNA mutation levels contribute to progeroid phenotypes came from the mtDNA mutator mouse. Recent evidence suggests that increases in aging-associated mtDNA mutations are not caused by damage accumulation, but rather are due to clonal expansion of mtDNA replication errors that occur during development. Here we discuss the caveats of the traditional mitochondrial free radical theory of aging and highlight other possible mechanisms, including insulin/IGF-1 signaling (IIS) and the target of rapamycin pathways, that underlie the central role of mitochondria in the aging process.
在过去的十年中，越来越多的证据表明线粒体功能障碍与衰老相关的主要表型之间存在因果关系。体细胞线粒体 DNA（mtDNA）突变和呼吸链功能障碍伴随着正常衰老，但增加的 mtDNA 突变水平导致类早衰表型的第一个直接实验证据来自 mtDNA 突变体小鼠。最近的证据表明，与衰老相关的 mtDNA 突变的增加不是由损伤积累引起的，而是由于在发育过程中 mtDNA 复制错误的克隆扩张引起的。在这里，我们讨论了传统的线粒体自由基衰老理论的局限性，并强调了其他可能的机制，包括胰岛素/IGF-1 信号（IIS）和雷帕霉素靶蛋白途径，这些机制是线粒体在衰老过程中起核心作用的基础。
