Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a large European population enrolled in the MARK-AGE study.
Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a large European population enrolled in the MARK-AGE study.
复制标题
DOI：
10.1111/acel.12485
复制
发表时间：
2016-08
期刊：
影响因子：
7.8
通讯作者：
Caiafa P
中科院分区：
文献类型：
--
作者：
Ciccarone F;Malavolta M;Calabrese R;Guastafierro T;Bacalini MG;Reale A;Franceschi C;Capri M;Hervonen A;Hurme M;Grubeck-Loebenstein B;Koller B;Bernhardt J;Schӧn C;Slagboom PE;Toussaint O;Sikora E;Gonos ES;Breusing N;Grune T;Jansen E;Dollé M;Moreno-Villanueva M;Sindlinger T;Bürkle A;Zampieri M;Caiafa P
衰老与DNA甲基化的内容和模式的改变有关，几乎贯穿整个人类寿命。这些差异的原因还不清楚。然而，一些证据表明，衰老中的表观遗传不稳定性可以追溯到DNA甲基转移酶表达的改变。在此，在MARK-AGE研究的背景下分析了DNA甲基转移酶DNMT 1和DNMT 3B的表达与年龄的相关性，MARK-AGE研究是一项针对欧洲普通人群的大规模横断面研究。使用外周血单核细胞，我们评估了在8个欧洲国家招募的2000多名年龄分层的女性和男性（35-75岁）中DNMT 1和DNMT 3B基因表达的变化。两种转录本均检测到显著的年龄相关变化。DNMT 1的水平随着年龄的增长而逐渐下降，但这仅在64岁之前观察到。相比之下，DNMT 3B的表达随着年龄的增加而线性下降，这种关联在女性中尤其明显。接下来，我们试图追踪这两种转录本的年龄相关变化，以了解不同变量的影响，这些变量会影响其在人群中的表达变化，包括人口统计学、饮食和健康习惯以及临床参数。我们的研究结果表明，年龄影响DNMT 1和DNMT 3B的表达作为一个几乎独立的变量在所有其他变量的评价。
Aging is associated with alterations in the content and patterns of DNA methylation virtually throughout the entire human lifespan. Reasons for these variations are not well understood. However, several lines of evidence suggest that the epigenetic instability in aging may be traced back to the alteration of the expression of DNA methyltransferases. Here, the association of the expression of DNA methyltransferases DNMT1 and DNMT3B with age has been analysed in the context of the MARK‐AGE study, a large‐scale cross‐sectional study of the European general population. Using peripheral blood mononuclear cells, we assessed the variation of DNMT1 and DNMT3B gene expression in more than two thousand age‐stratified women and men (35–75 years) recruited across eight European countries. Significant age‐related changes were detected for both transcripts. The level of DNMT1 gradually dropped with aging but this was only observed up to the age of 64 years. By contrast, the expression of DNMT3B decreased linearly with increasing age and this association was particularly evident in females. We next attempted to trace the age‐related changes of both transcripts to the influence of different variables that have an impact on changes of their expression in the population, including demographics, dietary and health habits, and clinical parameters. Our results indicate that age affects the expression of DNMT1 and DNMT3B as an almost independent variable in respect of all other variables evaluated.