Gao Xu, Zhang Yan, Breitling Lutz Philipp, Brenner Hermann
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Pneumology and Respiratory Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany.
Oncotarget. 2016 Jul 26;7(30):46878-46889. doi: 10.18632/oncotarget.9795.
Recent studies have identified biomarkers of chronological age based on DNA methylation levels. Since active smoking contributes to a wide spectrum of aging-related diseases in adults, this study intended to examine whether active smoking exposure could accelerate the DNA methylation age in forms of age acceleration (AA, residuals of the DNA methylation age estimate regressed on chronological age). We obtained the DNA methylation profiles in whole blood samples by Illumina Infinium Human Methylation450 Beadchip array in two independent subsamples of the ESTHER study and calculated their DNA methylation ages by two recently proposed algorithms. None of the self-reported smoking indicators (smoking status, cumulative exposure and smoking cessation time) or serum cotinine levels was significantly associated with AA. On the contrary, we successfully confirmed that 66 out of 150 smoking-related CpG sites were associated with AA, even after correction for multiple testing (FDR <0.05). We further built a smoking index (SI) based on these loci and demonstrated a monotonic dose-response relationship of this index with AA. In conclusion, DNA methylation-based biological indicators for current and past smoking exposure, but not self-reported smoking information or serum cotinine levels, were found to be related to DNA methylation defined AA. Further research should address potential mechanisms underlying the observed patterns, such as potential reflections of susceptibility to environmental hazards in both smoking related methylation changes and methylation defined AA.
最近的研究已经基于DNA甲基化水平确定了实足年龄的生物标志物。由于主动吸烟会导致成年人患多种与衰老相关的疾病，本研究旨在检验主动吸烟暴露是否会以年龄加速（AA，即DNA甲基化年龄估计值相对于实足年龄的残差）的形式加速DNA甲基化年龄。我们通过Illumina Infinium Human Methylation450 Beadchip芯片阵列在ESTHER研究的两个独立子样本中获取了全血样本的DNA甲基化谱，并通过两种最近提出的算法计算了它们的DNA甲基化年龄。自我报告的吸烟指标（吸烟状态、累积暴露量和戒烟时间）或血清可替宁水平均与年龄加速无显著关联。相反，我们成功证实，即使在多重检验校正后（FDR<0.05），150个与吸烟相关的CpG位点中有66个与年龄加速相关。我们进一步基于这些位点构建了一个吸烟指数（SI），并证明该指数与年龄加速呈单调剂量反应关系。总之，我们发现基于DNA甲基化的当前和过去吸烟暴露的生物指标与DNA甲基化定义的年龄加速相关，而不是自我报告的吸烟信息或血清可替宁水平。进一步的研究应探讨观察到的模式背后的潜在机制，例如吸烟相关甲基化变化和甲基化定义的年龄加速中对环境危害易感性的潜在反映。
