PDF(Pubmed)
Abstract：
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 genesPDE4C 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.
摘要：
可以将年龄相关CpG位点的DNA甲基化（DNAm）水平组合成表观遗传衰老特征以估计供体年龄。已经证明，这种表观遗传年龄预测和实际年龄之间的差异表明了晚年的全因死亡率。在这项研究中,我们测试了其他表观遗传特征,并遵循以下假设:即使是个体与年龄相关的CpG位点也可能是预期寿命的指标.使用99-CpG老化模型，在Lothian出生队列1921研究的DNAm资料中,5年以上的年龄预测与11%以上的死亡风险相关.然而,基于三个CpG的模型，甚至单个CpG，如果应用于独立的微阵列数据集，通常在年龄预测中显示出非常高的偏移量。另一方面,我们证明了在几个个体与年龄相关的CpG的DNAm水平似乎与预期寿命相关-例如，与基因PDE4C和CLCN6相关的CpG。我们的结果支持这样的观点，即小的老化特征应该通过更定量的方法来分析，如位点特异性焦磷酸测序，因为在独立的微阵列数据集上，年龄预测的精度相当低。然而，结果认为简单的表观遗传生物标志物，基于很少或个别与年龄相关的CpG，可以帮助估计生物年龄。
