Linnane A W, Baumer A, Maxwell R J, Preston H, Zhang C F, Marzuki S
Centre for Molecular Biology and Medicine, Monash University, Clayton, Victoria, Australia.
Biochem Int. 1990 Dec;22(6):1067-76.
Polymerase chain reaction (PCR) amplification was carried out on total DNA from a range of autopsy tissues from deceased human subjects with no known mitochondrial disease, aged from birth (80 minutes) to 87 years. We report the finding of an age-related 5 kb deletion in the mitochondrial genomes of these subjects. The deletion occurs between nucleotide positions 8470 and 13459 of the mitochondrial genome, and is flanked by a 13 bp direct repeat. All tissues from adult subjects showed the presence of mitochondrial DNA molecules with the deletion after a 30 cycle PCR amplification; by contrast the deletion was not similarly detected in any of the infant tissues analysed. However, the occurrence of the deletion was detected in the infant tissues after 60 PCR cycles of MtDNA amplification. It is concluded that such deletions are not necessarily associated with particular mitochondrial diseases but occur naturally, and with increasing frequency with age. A consequence of the accumulation of this deletion could be a progressive decrease with age of bioenergetic capacity which in turn could influence the rate of ageing and predispose to age-associated degenerative diseases.
对一系列来自无已知线粒体疾病的已故人类受试者的尸检组织的总DNA进行了聚合酶链反应（PCR）扩增，这些受试者年龄从出生（80分钟）到87岁不等。我们报告了在这些受试者的线粒体基因组中发现与年龄相关的5kb缺失。该缺失发生在线粒体基因组的核苷酸位置8470和13459之间，并由一个13bp的直接重复序列侧翼。在30个循环的PCR扩增后，成年受试者的所有组织均显示存在带有该缺失的线粒体DNA分子；相比之下，在分析的任何婴儿组织中均未类似地检测到该缺失。然而，在对线粒体DNA进行60个PCR循环扩增后，在婴儿组织中检测到了该缺失的发生。得出的结论是，此类缺失不一定与特定的线粒体疾病相关，而是自然发生的，并且随着年龄的增长频率增加。这种缺失积累的一个后果可能是生物能量能力随年龄增长而逐渐下降，这反过来又可能影响衰老速度并易患与年龄相关的退行性疾病。
