Distinct DNA methylation changes highly correlated with chronological age in the human brain

被引：289

作者：

Hernandez, Dena G. ^{[1
,3
,4
]}

Nalls, Michael A. ^{[1
]}

Gibbs, J. Raphael ^{[1
,3
,4
]}

Arepalli, Sampath ^{[1
]}

van der Brug, Marcel ^{[5
]}

Chong, Sean ^{[1
]}

Moore, Matthew ^{[1
]}

Longo, Dan L. ^{[2
]}

Cookson, Mark R. ^{[1
]}

Traynor, Bryan J. ^{[1
]}

Singleton, Andrew B. ^{[1
]}

机构：

[1] NIA, Neurogenet Lab, Baltimore, MD 21224 USA

[2] NIA, Lymphocyte Cell Biol Unit, Baltimore, MD 21224 USA

[3] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England

[4] UCL, Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England

[5] Scripps Res Inst, Dept Mol & Integrat Neurosci, Jupiter, FL USA

来源：

HUMAN MOLECULAR GENETICS | 2011年 / 20卷 / 06期

基金：

美国国家卫生研究院;

关键词：

DISEASES;

D O I：

10.1093/hmg/ddq561

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Methylation at CpG sites is a critical epigenetic modification in mammals. Altered DNA methylation has been suggested to be a central mechanism in development, some disease processes and cellular senescence. Quantifying the extent and identity of epigenetic changes in the aging process is therefore potentially important for understanding longevity and age-related diseases. In the current study, we have examined DNA methylation at > 27 000 CpG sites throughout the human genome, in frontal cortex, temporal cortex, pons and cerebellum from 387 human donors between the ages of 1 and 102 years. We identify CpG loci that show a highly significant, consistent correlation between DNA methylation and chronological age. The majority of these loci are within CpG islands and there is a positive correlation between age and DNA methylation level. Lastly, we show that the CpG sites where the DNA methylation level is significantly associated with age are physically close to genes involved in DNA binding and regulation of transcription. This suggests that specific age-related DNA methylation changes may have quite a broad impact on gene expression in the human brain.

引用

页码：1164 / 1172

页数：9

共 13 条

[11] Aging Mice Show a Decreasing Correlation of Gene Expression within Genetic Modules [J].