DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy.
DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy.
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DOI：
10.18632/aging.100908
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Wagner W
中科院分区：
文献类型：
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作者：
Lin Q;Weidner CI;Costa IG;Marioni RE;Ferreira MR;Deary IJ;Wagner W
年龄相关的CpG位点的DNA甲基化（DNAm）水平可以组合成表观遗传衰老特征来估计供体年龄。已经证明，这种表观遗传年龄预测和实足年龄之间的差异是晚年全因死亡率的指标。在这项研究中，我们测试了替代的表观遗传特征，并遵循了这样的假设，即即使是与年龄相关的CpG位点也可能指示预期寿命。使用99-CpG老化模型，在1921年洛锡安出生队列研究的DNA谱中，5岁以上的年龄预测与11%的死亡风险相关。然而，如果应用于独立的微阵列数据集，基于三个CpG，甚至单个CpG的模型通常会显示出非常高的年龄预测偏移。另一方面，我们证明了几个与年龄相关的CpG上的DNAm水平似乎与预期寿命相关-例如，在与基因PDE 4C和CLCN 6相关的CpG。我们的研究结果支持这样一种观点，即小的衰老特征应该通过更定量的方法进行分析，例如位点特异性焦磷酸测序，因为年龄预测的精度在独立的微阵列数据集上相当低。然而，这些结果认为，基于少数或个别年龄相关CpG的简单表观遗传生物标志物可以帮助估计生物年龄。
DNA-methylation (DNAm) levels at age-associated CpG sites can be combined into epigenetic aging signatures to estimate donor age. It has been demonstrated that the difference between such epigenetic age-predictions and chronological age is indicative for of all-cause mortality in later life. In this study, we tested alternative epigenetic signatures and followed the hypothesis that even individual age-associated CpG sites might be indicative for life-expectancy. Using a 99-CpG aging model, a five-year higher age-prediction was associated with 11% greater mortality risk in DNAm profiles of the Lothian Birth Cohort 1921 study. However, models based on three CpGs, or even individual CpGs, generally revealed very high offsets in age-predictions if applied to independent microarray datasets. On the other hand, we demonstrate that DNAm levels at several individual age-associated CpGs seem to be associated with life expectancy – e.g., at CpGs associated with the genes PDE4C and CLCN6. Our results support the notion that small aging signatures should rather be analysed by more quantitative methods, such as site-specific pyrosequencing, as the precision of age-predictions is rather low on independent microarray datasets. Nevertheless, the results hold the perspective that simple epigenetic biomarkers, based on few or individual age-associated CpGs, could assist the estimation of biological age.