Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates

被引：2582

作者：

Hannum, Gregory ^{[1
]}

Guinney, Justin ^{[5
]}

Zhao, Ling ^{[2
,3
,6
,7
]}

Zhang, Li ^{[2
,3
,6
,8
]}

Hughes, Guy ^{[2
,3
]}

Sadda, SriniVas ^{[9
]}

Klotzle, Brandy ^{[10
]}

Bibikova, Marina ^{[10
]}

Fan, Jian-Bing ^{[10
]}

Gao, Yuan ^{[11
]}

Deconde, Rob

Chen, Menzies

Rajapakse, Indika ^{[12
]}

Friend, Stephen ^{[5
]}

Ideker, Trey ^{[1
,2
,4
]}

Zhang, Kang ^{[2
,3
,6
,7
]}

机构：

[1] Univ Calif San Diego, Dept Bioengn, San Diego, CA 92093 USA

[2] Univ Calif San Diego, Inst Genom Med, San Diego, CA 92093 USA

[3] Univ Calif San Diego, Dept Ophthalmol, San Diego, CA 92093 USA

[4] Univ Calif San Diego, Dept Med, San Diego, CA 92093 USA

[5] Sage Bionetworks, Seattle, WA 98109 USA

[6] Sichuan Univ, Mol Med Res Ctr, Chengdu 610041, Peoples R China

[7] Sichuan Univ, Dept Ophthalmol, State Key Lab Biotherapy, W China Hosp, Chengdu 610041, Peoples R China

[8] Guangzhou IGenom, Guangzhou 510300, Peoples R China

[9] Univ So Calif, Doheny Eye Inst, Los Angeles, CA 90033 USA

[10] Illumina, San Diego, CA 92122 USA

[11] Johns Hopkins Univ, Lieber Inst, Baltimore, MD 21205 USA

[12] Fred Hutchinson Canc Res Ctr, Div Basic Sci & Biostat, Seattle, WA 98110 USA

来源：

MOLECULAR CELL | 2013年 / 49卷 / 02期

关键词：

DNA METHYLATION; GENE-EXPRESSION; EPIGENETICS; CANCER; AGE; REGULARIZATION; GENOTYPE;

D O I：

10.1016/j.molcel.2012.10.016

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：

The ability to measure human aging from molecular profiles has practical implications in many fields, including disease prevention and treatment, forensics, and extension of life. Although chronological age has been linked to changes in DNA methylation, the methylome has not yet been used to measure and compare human aging rates. Here, we build a quantitative model of aging using measurements at more than 450,000 CpG markers from the whole blood of 656 human individuals, aged 19 to 101. This model measures the rate at which an individual's methylome ages, which we show is impacted by gender and genetic variants. We also show that differences in aging rates help explain epigenetic drift and are reflected in the transcriptome. Moreover, we show how our aging model is upheld in other human tissues and reveals an advanced aging rate in tumor tissue. Our model highlights specific components of the aging process and provides a quantitative readout for studying the role of methylation in age-related disease.

引用

页码：359 / 367

页数：9

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