Melov S, Shoffner J M, Kaufman A, Wallace D C
Department of Genetics and Molecular Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
Nucleic Acids Res. 1995 Oct 25;23(20):4122-6. doi: 10.1093/nar/23.20.4122.
Several reports have shown that individual mitochondrial DNA (mtDNA) deletions accumulate with age. However, the overall extent of somatic mtDNA damage with age remains unclear. We have utilized full-length PCR to concurrently screen for multiple mtDNA rearrangements in total DNA extracted from skeletal muscle derived from physiologically normal individuals (n = 35). This revealed that both the number and variety of mtDNA rearrangements increases dramatically between young and old individuals (P < 0.0001). We further examined the mtDNA from both the younger and older subjects by Southern blot analysis and observed an age-related increase in mtDNA(s) comparable in size to mtDNA products unique to patients with known mtDNA deletions. These data imply that a wide spectrum of mtDNA rearrangements accumulate in old individuals, which correlates with the marked age related decrease in OXPHOS capacity observed in post-mitotic tissues.
多项报告显示，个体线粒体DNA（mtDNA）缺失会随年龄增长而积累。然而，随着年龄增长，体细胞mtDNA损伤的总体程度仍不清楚。我们利用全长PCR技术，同时筛选从生理正常个体（n = 35）的骨骼肌中提取的总DNA中的多种mtDNA重排。结果显示，年轻个体与老年个体之间，mtDNA重排的数量和种类均显著增加（P < 0.0001）。我们通过Southern印迹分析进一步检测了年轻和老年受试者的mtDNA，观察到与已知mtDNA缺失患者特有的mtDNA产物大小相当的mtDNA随年龄增长而增加。这些数据表明，老年个体中积累了广泛的mtDNA重排，这与在有丝分裂后组织中观察到的与年龄相关的氧化磷酸化（OXPHOS）能力显著下降相关。
