Age-associated change in mitochondrial DNA damage
Age-associated change in mitochondrial DNA damage
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DOI：
10.1080/10715769800300611
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发表时间：
1998-01-01
影响因子：
3.3
通讯作者：
Hansford, RG
中科院分区：
文献类型：
--
作者：
Hudson, EK;Hogue, BA;Hansford, RG
Wistar大鼠心脏的线粒体功能存在与年龄相关的下降。本实验室以前的报告显示，线粒体细胞色素c氧化酶（考克斯）活性降低与考克斯基因和蛋白表达降低以及线粒体蛋白合成速率类似降低相关。使用HPLC-Coularray系统（ESA，USA），我们测量了来自6个月（年轻）和23个月（衰老）大鼠肝脏DNA的核和线粒体8-氧代-2 '-脱氧鸟苷（8-oxodG）的水平。我们通过用光敏亚甲蓝损伤小牛胸腺DNA 30 s至2 h来测量该技术的灵敏度。损伤水平在整个时间过程中呈线性，包括较短的时间，其显示水平与肝脏中的预期水平相当。对于肝脏数据，8-oxodG报告为2-脱氧鸟苷（2-dG）的一部分。从6月龄到23月龄，核DNA中8-oxodG水平没有变化。然而，随着年龄的增长，线粒体DNA中的8-oxodG水平增加了2.5倍。在6个月时，mtDNA中的8-oxodG水平比核高5倍，到23个月时增加到约12倍。这些发现与其他报告一致，显示线粒体DNA损伤水平与年龄相关;然而，它增加的程度较小，线粒体DNA的这种损伤可能导致线粒体功能与年龄相关的下降。
There is an age-associated decline in the mitochondrial function of the Wistar rat heart. Previous reports from this lab have shown a decrease in mitochondrial cytochrome c oxidase (COX) activity associated with a reduction in COX gene and protein expression and a similar decrease in the rate of mitochondrial protein synthesis. Damage to mitochondrial DNA may contribute to this decline.Using the HPLC-Coularray system (ESA, USA), we measured levels of nuclear and mitochondrial 8-oxo-2'-deoxyguanosine (8-oxodG) from 6-month (young) and 23-month-old (senescent) rat liver DNA. We measured the sensitivity of the technique by damaging calf thymus DNA with photoactivated methylene blue for 30 s up to 2 h. The levels of damage were linear over the entire time course including the shorter times which showed levels comparable to those expected in liver. For the liver data, 8-oxodG was reported as a fraction of 2-deoxyguanosine (2-dG). There was no change in the levels of 8-oxodG levels in the nuclear DNA from 6 to 23-months of age. However, the levels of 8-oxodG increased 2.5-fold in the mitochondrial DNA with age. At 6 months, the level of 8-oxodG in mtDNA was 5-fold higher than nuclear and increased to approximately 12-fold higher by 23 months of age. These findings agree with other reports showing an age-associated increase in levels of mtDNA damage; however, the degree to which it increases is smaller Such damage to the mitochondrial DNA may contribute to the age-associated decline in mitochondrial function.