The 4977 bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: A useful biomarker or more?
The 4977 bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: A useful biomarker or more?
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DOI：
10.1016/j.exger.2008.03.004
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发表时间：
2008-07-01
影响因子：
3.9
通讯作者：
Oehmichen, Manfred
中科院分区：
文献类型：
--
作者：
Meissner, Christoph;Bruse, Petra;Oehmichen, Manfred
有人认为，线粒体DNA（mtDNA）的缺失是衰老过程中的重要因素。自20世纪90年代初以来，4977 bp的缺失已在各种组织中进行了研究，特别是在有丝分裂后的组织具有高能量需求。不幸的是，其中一些研究包括不到10个主题，所以我们的研究目的。在一个92人的队列中，可靠地量化人类大脑、心脏和骨骼肌的9个不同区域的缺失量。基底神经节含有最高的缺失量，其值高达2.93%，青春期早期和老年人之间的缺失水平差异高达三个数量级。额叶中的数值平均低一个数量级，但小脑组织中的数值最低，平均仅为基底神经节的5 x 10（-3）。缺失在40岁早期开始在髂腰肌中积累，值在0.00019%和0.0035%之间，在102岁女性中最高，为0.14%。与骨骼肌相比，左心室心肌中的总丰度仅为三分之一。黑质缺失量与年龄的线性对数相关性最好，r = 0.87（p <0.0005），其次是左室前壁（r = 0.82; p <0.0005）。关于线粒体DNA损伤，我们建议使用4977 bp的缺失作为一个理想的生物标志物来区分生理老化和加速老化。线粒体缺失在衰老过程中的生物学意义正在讨论中，但有实验证据表明，大规模的缺失损害了单个细胞中的氧化磷酸化，并使这些细胞敏感，从而发生凋亡。(C)2008年爱思唯尔公司All rights reserved.
it has been suggested that deletions of mitochondrial DNA (mtDNA) are important players with regard to the ageing process. Since the early 1990s, the 4977 bp deletion has been studied in various tissues, especially in postmitotic tissues with high energy demand. Unfortunately, some of these studies included less than 10 subjects, so the aim of our study. was to quantify reliably the deletion amount in nine different regions of human brain, heart and skeletal muscle in a cohort of 92 individuals. The basal ganglia contain the highest deletion amounts with values up to 2.93% and differences in deletion levels between early adolescence and older ages were up to three orders of magnitude. Values in frontal lobe were on average an order of magnitude lower, but lowest in cerebellar tissue where the amount was on average only 5 x 10(-3) of the basal ganglia. The deletion started to accumulate in iliopsoas muscle early in the fourth decade of life with values between 0.00019% and 0.0035% and was highest in a 102-year-old woman with 0.14%. In comparison to skeletal muscle, the overall abundance in heart muscle of the left ventricle was only one-third. The best linear logarithmic correlation between amount of the deletion and age was found in substantia nigra with r = 0.87 (p < 0.0005) followed by anterior wall of the left ventricle (r = 0.82; p < 0.0005). With regard to mitochondrial DNA damage, we propose to use the 4977 bp deletion as an ideal biomarker to discriminate between physiological ageing and accelerated ageing. The biological meaning of mitochondrial deletions in the process of ageing is under discussion, but there is experimental evidence that large-scale deletions impair the oxidative phosphorylation in single cells and sensitize these cells to undergo apoptosis. (C) 2008 Elsevier Inc. All rights reserved.