Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195-7705, USA.
Mech Ageing Dev. 2012 Apr;133(4):118-26. doi: 10.1016/j.mad.2011.10.009. Epub 2011 Nov 3.
The somatic mutation theory of aging posits that the accumulation of mutations in the genetic material of somatic cells as a function of time results in a decrease in cellular function. In particular, the accumulation of random mutations may inactivate genes that are important for the functioning of the somatic cells of various organ systems of the adult, result in a decrease in organ function. When the organ function decreases below a critical level, death occurs. A significant amount of research has shown that somatic mutations play an important role in aging and a number of age related pathologies. In this review, we explore evidence for increases in somatic nuclear mutation burden with age and the consequences for aging, cancer, and neurodegeneration. We then review evidence for increases in mitochondrial mutation burden and the consequences for dysfunction in the disease processes.
衰老的体细胞突变理论认为，随着时间的推移，体细胞遗传物质中突变的积累会导致细胞功能下降。特别是，随机突变的积累可能会使对各种器官系统体细胞功能很重要的基因失活，导致器官功能下降。当器官功能下降到临界水平以下时，就会死亡。大量研究表明，体细胞突变在衰老和许多与年龄相关的病理中起着重要作用。在这篇综述中，我们探讨了随年龄增长体细胞核突变负担增加的证据及其对衰老、癌症和神经退行性变的影响。然后，我们回顾了线粒体突变负担增加的证据及其对疾病过程中功能障碍的影响。
