Frailty is associated with the epigenetic clock but not with telomere length in a German cohort.
Frailty is associated with the epigenetic clock but not with telomere length in a German cohort.
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DOI：
10.1186/s13148-016-0186-5
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发表时间：
2016
影响因子：
5.7
通讯作者：
Brenner H
中科院分区：
文献类型：
--
作者：
Breitling LP;Saum KU;Perna L;Schöttker B;Holleczek B;Brenner H
表观遗传时钟，特别是由所谓的DNA甲基化年龄加速量化的表观遗传前期衰老，最近被认为与各种疾病表型密切相关。然而，它与端粒长度和脆性的关系仍然缺乏数据，端粒长度和脆性分别可以被认为是基因组和临床水平上年龄的主要相关性。在这项横断面观察性研究中，来自德国老年人群队列研究的两个子集(n = 969和n = 851；平均 ± 标准差年龄分别为62.1 ±dna 6.5和63.0 ±dna 6.7)的1820名受试者，根据先前在一项大型元研究中开发的353个基因座预测因子计算了 甲基化年龄，并根据预测的甲基化年龄减去时间年龄计算了基于差异的表观遗传年龄加速。在我们的研究中，没有发现表观遗传年龄加速与端粒长度相关(p = 0.63)。然而，DNA甲基化年龄加速与综合脆弱程度有关，因此累积的缺陷随着年龄加速而显著增加。从数量上讲，每6年甲基化年龄加速就会增加大约一半的缺陷(p = 0.0004)。这种相关性独立于年龄、性别和估计的白细胞分布，也不受考虑的其他各种混杂变量的影响。本研究的结果表明，表观遗传年龄加速通过与端粒长度评估的细胞衰老无关的途径与临床相关的衰老相关表型相关。需要像孟德尔随机化这样的创新方法来阐明表观遗传年龄加速是否确实对临床表型的发展起到了因果作用。本文的在线版本(doi：10.1186/s131480160186-5)包含补充材料，授权用户可以使用。
The epigenetic clock, in particular epigenetic pre-aging quantified by the so-called DNA methylation age acceleration, has recently been suggested to closely correlate with a variety of disease phenotypes. There remains a dearth of data, however, on its association with telomere length and frailty, which can be considered major correlates of age on the genomic and clinical level, respectively. In this cross-sectional observational study on altogether 1820 subjects from two subsets (n = 969 and n = 851; mean ± standard deviation age 62.1 ± 6.5 and 63.0 ± 6.7 years, respectively) of the ESTHER cohort study of the elderly general population in Germany, DNA methylation age was calculated based on a 353 loci predictor previously developed in a large meta-study, and the difference-based epigenetic age acceleration was calculated as predicted methylation age minus chronological age. No correlation of epigenetic age acceleration with telomere length was found in our study (p = 0.63). However, there was an association of DNA methylation age acceleration with a comprehensive frailty measure, such that the accumulated deficits significantly increased with increasing age acceleration. Quantitatively, about half an additional deficit was added per 6 years of methylation age acceleration (p = 0.0004). This association was independent from age, sex, and estimated leukocyte distribution, as well as from a variety of other confounding variables considered. The results of the present study suggest that epigenetic age acceleration is correlated with clinically relevant aging-related phenotypes through pathways unrelated to cellular senescence as assessed by telomere length. Innovative approaches like Mendelian randomization will be needed to elucidate whether epigenetic age acceleration indeed plays a causal role for the development of clinical phenotypes. The online version of this article (doi:10.1186/s13148-016-0186-5) contains supplementary material, which is available to authorized users.