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动物器官中的衰老和氧化损伤的核 DNA。

Aging and oxidatively damaged nuclear DNA in animal organs.

机构信息

Section of Environmental Health, Department of Public Health, University of Copenhagen, DK-1014 Copenhagen K, Denmark.

出版信息

Free Radic Biol Med. 2010 May 15;48(10):1275-85. doi: 10.1016/j.freeradbiomed.2010.02.003. Epub 2010 Feb 10.

Abstract

Oxidative stress is considered to contribute to aging and is associated with the generation of oxidatively damaged DNA, including 8-oxo-7,8-dihydroguanine. We have identified 69 studies that have measured the level of oxidatively damaged DNA in organs of animals at various ages. In general, organs with limited cell proliferation, i.e., liver, kidney, brain, heart, pancreas, and muscle, tended to show accumulation of DNA damage with age, whereas organs with highly proliferating cells, such as intestine, spleen, and testis, showed more equivocal or no effect of age. A restricted analysis of studies reporting a baseline level of damaged DNA that was fewer than 5 lesions/10(6) dG showed that 21 of 29 studies reported age-associated accumulation of DNA damage. The standardized mean difference in oxidatively damaged DNA between the oldest and the youngest age groups was 1.49 (95% CI 1.03-1.95). There was no difference between age span, number of tested organs, statistical power, sex, strain, or breeding between the studies showing positive and null effects. Citation and publication bias seems to be a problem in the overall dataset, whereas it is less pronounced in the restricted dataset. There is compelling evidence for aging-associated accumulation of oxidatively damaged DNA in organs with limited cell proliferation.

摘要

氧化应激被认为与衰老有关,并且与氧化性 DNA 损伤的产生有关,包括 8-氧代-7,8-二氢鸟嘌呤。我们已经确定了 69 项研究,这些研究测量了不同年龄动物器官中氧化性 DNA 损伤的水平。一般来说,细胞增殖能力有限的器官,如肝脏、肾脏、大脑、心脏、胰腺和肌肉,随着年龄的增长往往会积累 DNA 损伤,而增殖能力较强的器官,如肠道、脾脏和睾丸,则表现出更为不确定或没有年龄影响。对报告少于 5 个损伤/10(6)dG 的基线损伤 DNA 水平的研究进行的限制性分析表明,29 项研究中有 21 项报告了与年龄相关的 DNA 损伤积累。在最老和最年轻年龄组之间,氧化损伤 DNA 的标准化均数差为 1.49(95%CI 1.03-1.95)。在表现出阳性和阴性效应的研究之间,年龄跨度、测试器官数量、统计能力、性别、品系或繁殖方式没有差异。引用和出版偏倚似乎是整个数据集的一个问题,而在限制数据集则不那么明显。有强有力的证据表明,有限细胞增殖的器官中与衰老相关的氧化性 DNA 损伤积累。

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