Mutation and intracellular clonal expansion of mitochondrial genomes: two synergistic components of the aging process?
Mutation and intracellular clonal expansion of mitochondrial genomes: two synergistic components of the aging process?
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DOI：
10.1016/s0047-6374(02)00169-0
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发表时间：
2003-01-01
影响因子：
5.3
通讯作者：
Khrapko, K
中科院分区：
文献类型：
--
作者：
Kraytsberg, Y;Nekhaeva, E;Khrapko, K
线粒体衰老突变理论的基础包括两个假设：线粒体突变的高度丰度及其在单个细胞内克隆扩展的能力。回顾了与这些假设相关的最新数据，并提供了突变频率和细胞内扩展的半定量估计。在不同的衰老组织中，突变的发生率可能在每个线粒体基因组拷贝一个突变的数量级上，并且大多数细胞可能受到线粒体基因组的细胞内克隆扩张的影响。因此，衰老组织可以被认为是具有不同突变线粒体基因型的细胞的马赛克。有趣的是，独立的研究表明，广泛的老化组织呈现出具有不同线粒体表型的细胞的马赛克。可以使用必要的方法来探索这两个马赛克是否存在因果关系。答案显然在肌肉中是肯定的；其他组织，特别是大脑，还有待探索。(C)2002爱思唯尔科学爱尔兰有限公司。保留所有权利。
The foundations of the Mitochondrial mutational theory of aging include two assumptions: the high abundance of mitochondrial mutations and their ability to clonally expand within individual cells. The up-to-date data pertinent to these assumptions is reviewed and semi-quantitative estimates of the frequencies of mutants and intracellular expansions are offered. The incidence of mutations in various aged tissues may be on the order of one mutant per mitochondrial genome copy, and most of the cells are likely to be affected by intracellular clonal expansions of mitochondrial genomes. Thus aged tissue may be considered a mosaic of cells with different mutant mitochondrial genotypes. Interestingly, independent studies show that a wide range of aged tissues presents with a mosaic of cells with different mitochondrial phenotypes. The necessary methodologies are available to explore whether the two mosaics are causally related. The answer apparently is positive in muscle; other tissues, brain in particular, await exploration. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.