Michikawa Y, Mazzucchelli F, Bresolin N, Scarlato G, Attardi G
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Science. 1999 Oct 22;286(5440):774-9. doi: 10.1126/science.286.5440.774.
Progressive damage to mitochondrial DNA (mtDNA) during life is thought to contribute to aging processes. However, this idea has been difficult to reconcile with the small fraction of mtDNA so far found to be altered. Here, examination of mtDNA revealed high copy point mutations at specific positions in the control region for replication of human fibroblast mtDNA from normal old, but not young, individuals. Furthermore, in longitudinal studies, one or more mutations appeared in an individual only at an advanced age. Some mutations appeared in more than one individual. Most strikingly, a T414G transversion was found, in a generally high proportion (up to 50 percent) of mtDNA molecules, in 8 of 14 individuals above 65 years of age (57 percent) but was absent in 13 younger individuals.
线粒体DNA（mtDNA）在生命过程中的渐进性损伤被认为与衰老过程有关。然而，这一观点很难与目前发现的仅一小部分发生改变的mtDNA相协调。在此，对mtDNA的检测发现，在正常老年人而非年轻人的人类成纤维细胞mtDNA复制控制区的特定位置存在高拷贝点突变。此外，在纵向研究中，一个或多个突变仅在个体高龄时出现。一些突变出现在不止一个个体中。最引人注目的是，在14名65岁以上个体中的8名（57%）中，在通常很高比例（高达50%）的mtDNA分子中发现了T414G颠换，但在13名较年轻个体中未发现。
