Mecocci P, MacGarvey U, Kaufman A E, Koontz D, Shoffner J M, Wallace D C, Beal M F
Neurochemistry Laboratory, Massachusetts General Hospital, Boston 02114.
Ann Neurol. 1993 Oct;34(4):609-16. doi: 10.1002/ana.410340416.
A major theory of aging is that oxidative damage may accumulate in DNA and contribute to physiological changes associated with aging. We examined age-related accumulation of oxidative damage to both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in human brain tissue. We measured the oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (OH8dG), in DNA isolated from 3 regions of cerebral cortex and cerebellum from 10 normal humans aged 42 to 97 years. The amount of OH8dG, expressed as a ratio of the amount of deoxyguanosine (dG) or as fmol/micrograms of DNA, increased progressively with normal aging in both nDNA and mtDNA; however, the rate of increase with age was much greater in mtDNA. There was a significant 10-fold increase in the amount of OH8dG in mtDNA as compared with nDNA in the entire group of samples, and a 15-fold significant increase in patients older than 70 years. These results show for the first time that there is a progressive age-related accumulation in oxidative damage to DNA in human brain, and that the mtDNA is preferentially affected. It is possible that such damage may contribute to age-dependent increases in incidence of neurodegenerative diseases.
衰老的一个主要理论是氧化损伤可能在DNA中积累，并导致与衰老相关的生理变化。我们研究了人类脑组织中核DNA（nDNA）和线粒体DNA（mtDNA）氧化损伤的年龄相关性积累。我们测量了从10名年龄在42至97岁的正常人类的大脑皮层和小脑的3个区域分离出的DNA中的氧化核苷8-羟基-2'-脱氧鸟苷（OH8dG）。以脱氧鸟苷（dG）的量的比率或每微克DNA的飞摩尔数表示的OH8dG的量，在nDNA和mtDNA中均随着正常衰老而逐渐增加；然而，mtDNA中随年龄的增加速率要大得多。在整个样本组中，mtDNA中OH8dG的量与nDNA相比显著增加了10倍，在70岁以上的患者中显著增加了15倍。这些结果首次表明，人类大脑中DNA的氧化损伤存在与年龄相关的渐进性积累，并且mtDNA受到的影响更为明显。这种损伤可能导致神经退行性疾病发病率随年龄增长而增加。
