Annett Kathryn, Hyland Paul, Duggan Orla, Barnett Christopher, Barnett Yvonne
Cancer and Ageing Research Group, School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, BT52 1SA, UK.
Exp Gerontol. 2004 Apr;39(4):491-8. doi: 10.1016/j.exger.2003.09.028.
DNA damage has been shown to increase with age in lymphocytes of healthy humans and in human CD4+ T cell clones. Such genetic damage, if unrepaired, may have a detrimental effect on lymphocyte-mediated immune responses. This study investigated DNA excision repair capacity of human CD4+ T cell clones as a function of age in vitro. Cultures of T cell clones were treated with a range of DNA damaging agents; hydrogen peroxide, N-methyl-N'-nitro-N-nitrosoguanidine or 254 nm ultraviolet irradiation. Following treatment, the amount of DNA damage in the clones was determined over a time course using modified comet assays. The results obtained revealed a decline related to in vitro age in the DNA repair capacity of clones derived from a 26 and a 45 year old donor. This decline may represent at least a partial explanation for the age related increase in DNA damage in these clones when cultured in vitro. In contrast, there was no evidence for a decline related to in vitro age in repair capacity in the clones derived from an 80 year old SENIEUR donor. An alternative mechanism must underlie the age related increased in DNA damage in these clones when cultured in vitro.
已有研究表明，健康人的淋巴细胞以及人类CD4+ T细胞克隆中的DNA损伤会随着年龄的增长而增加。这种基因损伤若不修复，可能会对淋巴细胞介导的免疫反应产生不利影响。本研究在体外调查了人类CD4+ T细胞克隆的DNA切除修复能力与年龄的关系。用一系列DNA损伤剂处理T细胞克隆培养物；过氧化氢、N-甲基-N'-硝基-N-亚硝基胍或254纳米紫外线照射。处理后，使用改良彗星试验在一段时间内测定克隆中的DNA损伤量。所得结果显示，来自26岁和45岁供体的克隆的DNA修复能力与体外年龄有关，呈下降趋势。这种下降可能至少部分解释了这些克隆在体外培养时DNA损伤随年龄增长的现象。相比之下，没有证据表明来自80岁SENIEUR供体的克隆的修复能力与体外年龄有关，呈下降趋势。在体外培养时，这些克隆中与年龄相关的DNA损伤增加必然存在另一种机制。
