Mitochondrial point mutations do not limit the natural lifespan of mice
Mitochondrial point mutations do not limit the natural lifespan of mice
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DOI：
10.1038/ng1988
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发表时间：
2007-04-01
期刊：
影响因子：
30.8
通讯作者：
Loeb, Lawrence A.
中科院分区：
文献类型：
--
作者：
Vermulst, Marc;Bielas, Jason H.;Loeb, Lawrence A.
线粒体突变是否导致哺乳动物衰老，或者仅仅与之相关，是一个激烈争论的领域(1)。在这里，我们使用一种新的，高度敏感的分析(2)来重新定义线粒体突变和年龄之间的关系。我们测量了小鼠线粒体基因组在单碱基对水平上的体内变化率，并证明小鼠线粒体的突变频率比先前报道的低十倍以上。尽管我们观察到随着年龄的增长，线粒体点突变增加了11倍，但我们报告说，线粒体突变小鼠(3)能够承受比正常小鼠高500倍的突变负担，而没有任何明显的快速加速衰老的特征。因此，我们的结果强烈表明，线粒体突变不会限制野生型小鼠的寿命。
Whether mitochondrial mutations cause mammalian aging, or are merely correlated with it, is an area of intense debate(1). Here, we use a new, highly sensitive assay(2) to redefine the relationship between mitochondrial mutations and age. We measured the in vivo rate of change of the mitochondrial genome at a single-base pair level in mice, and we demonstrate that the mutation frequency in mouse mitochondria is more than ten times lower than previously reported. Although we observed an 11-fold increase in mitochondrial point mutations with age, we report that a mitochondrial mutator mouse(3) was able to sustain a 500-fold higher mutation burden than normal mice, without any obvious features of rapidly accelerated aging. Thus, our results strongly indicate that mitochondrial mutations do not limit the lifespan of wild-type mice.