HIV-1 Infection Accelerates Age According to the Epigenetic Clock.
HIV-1 Infection Accelerates Age According to the Epigenetic Clock.
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DOI：
10.1093/infdis/jiv277
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发表时间：
2015-11-15
期刊：
影响因子：
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通讯作者：
Levine AJ
中科院分区：
文献类型：
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作者：
Horvath S;Levine AJ
背景：人类免疫缺陷病毒1型（HIV）感染与加速衰老的临床症状有关，这一点可从相对年轻时年龄相关疾病的发病率和多样性增加以及器官和细胞病理学分析的支持性发现中得到证实。 但在分子水平上检测加速老化效应一直很困难。方法：在这里，我们使用了一种基于宿主DNA甲基化水平的衰老表观遗传生物标志物来研究HIV感染对加速衰老的影响。 通过Illumina Infinium Methylation 450 K平台测定来自脑和血液组织的DNA。结果：使用6个新的DNA甲基化数据集，我们发现HIV感染导致脑组织（7.4岁）和血液（5.2岁）的表观遗传年龄增加。 虽然在血液中观察到的加速老化效应可能反映了血细胞成分的变化（特别是细胞毒性T细胞的耗竭），但尚不清楚如何解释在脑组织中观察到的加速老化效应。结论：总的来说，我们的研究结果表明，表观遗传时钟是一个有用的生物标志物检测加速老化的影响，由于艾滋病毒感染。 该工具可用于准确确定个体组织和细胞中的老化加速程度。
Background. Infection with human immunodeficiency virus type 1 (HIV) is associated with clinical symptoms of accelerated aging, as evidenced by the increased incidence and diversity of age-related illnesses at relatively young ages and supporting findings of organ and cellular pathologic analyses. But it has been difficult to detect an accelerated aging effect at a molecular level. Methods. Here, we used an epigenetic biomarker of aging based on host DNA methylation levels to study accelerated aging effects due to HIV infection. DNA from brain and blood tissue was assayed via the Illumina Infinium Methylation 450 K platform. Results. Using 6 novel DNA methylation data sets, we show that HIV infection leads to an increase in epigenetic age both in brain tissue (7.4 years) and blood (5.2 years). While the observed accelerated aging effects in blood may reflect changes in blood cell composition (notably exhausted cytotoxic T cells), it is less clear what explains the observed accelerated aging effects in brain tissue. Conclusions. Overall, our results demonstrate that the epigenetic clock is a useful biomarker for detecting accelerated aging effects due to HIV infection. This tool can be used to accurately determine the extent of age acceleration in individual tissues and cells.