Cell-by-cell scanning of whole mitochondrial genomes in aged human heart reveals a significant fraction of myocytes with clonally expanded deletions
Cell-by-cell scanning of whole mitochondrial genomes in aged human heart reveals a significant fraction of myocytes with clonally expanded deletions
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DOI：
10.1093/nar/27.11.2434
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发表时间：
1999-06-01
影响因子：
14.9
通讯作者：
Wei, JY
中科院分区：
文献类型：
--
作者：
Khrapko, K;Bodyak, N;Wei, JY
年轻和老年组织中所有可能的线粒体DNA（mtDNA）突变的细胞间分布的定量信息，需要评估这些突变与衰老过程的相关性。在本研究中，我们使用PCR扩增来自单个细胞的全长线粒体基因组来扫描人类心肌细胞中所有可能的mtDNA大缺失，对来自三名中年和四名百岁老人供体的350多个单个细胞的分析表明，虽然大多数细胞不包含缺失，但在某些心肌细胞中，mtDNA分子的显著部分携带一种特定的缺失。不同的受影响细胞含有不同的缺失。尽管每个捐赠者筛选的细胞数量相似，但这些缺失丰富的细胞仅在老年捐赠者的心脏中发现，它们的发生频率高达七分之一。这些初步观察结果证明了该方法的有效性，并表明线粒体突变有可能在人类心肌衰老中发挥重要作用。
Quantitative information on the cell-to-cell distribution of all possible mitochondrial DNA (mtDNA) mutations in young and aged tissues is needed to assess the relevance of these mutations to the aging process. In the present study, we used PCR amplification of full-length mitochondrial genomes from single cells to scan human cardiomyocytes for all possible large deletions in mtDNA, Analysis of more than 350 individual cells that were derived from three middle-aged and four centenarian donors demonstrates that while most of the cells contain no deletions, in certain cardiomyocytes a significant portion of the mtDNA molecules carried one particular deletion. Different affected cells contained different deletions. Although similar numbers of cells were screened for each donor, these deletion-rich cells were found only in the hearts of old donors, where they occurred at a frequency of up to one in seven cells. These initial observations demonstrate the efficiency of the method and indicate that mitochondrial mutations have the potential to play an important role in human myocardial aging.