Lack of age-related increase of mitochondrial DNA amount in brain, skeletal muscle and human heart
Lack of age-related increase of mitochondrial DNA amount in brain, skeletal muscle and human heart
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DOI：
10.1016/j.mad.2005.06.008
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发表时间：
2005-11-01
影响因子：
5.3
通讯作者：
Meissner, C
中科院分区：
文献类型：
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作者：
Frahm, T;Mohamed, SA;Meissner, C
在衰老过程中，据报道线粒体DNA（mtDNA）缺失及其他突变有所增加。mtDNA的这些结构改变被认为会导致呼吸链活性降低，并可能促进衰老过程。因此，出现了这样一个问题：体内缺失的mtDNA的积累是否通过反馈机制使mtDNA合成增加而得到补偿。我们设计了两种人mtDNA特异性寡核苷酸探针，用于对50个年龄从8周龄到93岁的个体的5种不同组织进行mtDNA定量分析。尾状核中mtDNA的量约为1.1±0.5%（4617±2099拷贝），额叶皮质中为1.0±0.5%（4198±2099拷贝），小脑皮质中为0.3±0.2%（1259±840拷贝），骨骼肌中为1.0±0.4%（4198±1679拷贝），心肌中为2.2±1.3%（9235±5457拷贝）。我们在5种不同组织的衰老过程中未观察到绝对拷贝数有任何显著变化，因此，没有发现所假定的反馈机制存在的证据。我们的研究表明，mtDNA拷贝数具有组织特异性，并取决于组织的能量需求。（c）2005爱思唯尔爱尔兰有限公司。保留所有权利。
During the ageing process, an increase of mitochondrial DNA (mtDNA) deletions and other mutations have been reported. These structural alterations of mtDNA are assumed to cause a reduction in the respiratory chain activity and may contribute to the ageing process. Therefore, the question arises if the accumulation of deleted mtDNA is compensated in vivo by an increase of mtDNA synthesis via a feedback mechanism. We designed two human mtDNA-specific oligonucleotide probes for quantitative mtDNA analysis of 5 different tissues from 50 individuals aged from 8 weeks to 93 years. The amount of mtDNA was approximately 1.1 +/- 0.5% (4617 +/- 2099 copies) in the caudate nucleus, 1.0 +/- 0.5% (4198 +/- 2099 copies) in the frontal lobe cortex, 0.3 +/- 0.2% (1259 +/- 840 copies) in the cerebellar cortex, 1.0 +/- 0.4% (4198 +/- 1679 copies) in skeletal muscle and 2.2 +/- 1.3% (9235 +/- 5457 copies) in heart muscle. We did not observe any significant change in the absolute copy number during ageing in five different tissues, and therefore, found no evidence for the postulated feedback mechanism. Our study indicates that mtDNA copy number is tissue-specific and depends on the energy demand of the tissue. (c) 2005 Elsevier Ireland Ltd. All rights reserved.