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

被引：2663

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

共 51 条

[1] Age-associated DNA methylation in pediatric populations [J].

Alisch, Reid S. ;

Barwick, Benjamin G. ;

Chopra, Pankaj ;

Myrick, Leila K. ;

Satten, Glen A. ;

Conneely, Karen N. ;

Warren, Stephen T. .

GENOME RESEARCH, 2012, 22 (04) :623-632

[2]

[Anonymous], 1963, The Mathematical Theory of Communication

[3] Lipoprotein genotype and conserved pathway for exceptional longevity in humans [J].

Atzmon, G ;

Rincon, M ;

Schechter, CB ;

Shuldiner, AR ;

Lipton, RB ;

Bergman, A ;

Barzilai, N .

PLOS BIOLOGY, 2006, 4 (04) :562-569

[4]

Austad Steven N, 2006, Gend Med, V3, P79, DOI 10.1016/S1550-8579(06)80198-1

[5] DNA methylation in metabolic disorders [J].

Barres, Romain ;

Zierath, Juleen R. .

AMERICAN JOURNAL OF CLINICAL NUTRITION, 2011, 93 (04) :897S-900S

[6] Epigenome-Wide Scans Identify Differentially Methylated Regions for Age and Age-Related Phenotypes in a Healthy Ageing Population [J].

Bell, Jordana T. ;

Tsai, Pei-Chien ;

Yang, Tsun-Po ;

Pidsley, Ruth ;

Nisbet, James ;

Glass, Daniel ;

Mangino, Massimo ;

Zhai, Guangju ;

Zhang, Feng ;

Valdes, Ana ;

Shin, So-Youn ;

Dempster, Emma L. ;

Murray, Robin M. ;

Grundberg, Elin ;

Hedman, Asa K. ;

Nica, Alexandra ;

Small, Kerrin S. ;

Dermitzakis, Emmanouil T. ;

McCarthy, Mark I. ;

Mill, Jonathan ;

Spector, Tim D. ;

Deloukas, Panos .

PLOS GENETICS, 2012, 8 (04) :189-200

[7] DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines [J].

Bell, Jordana T. ;

Pai, Athma A. ;

Pickrell, Joseph K. ;

Gaffney, Daniel J. ;

Pique-Regi, Roger ;

Degner, Jacob F. ;

Gilad, Yoav ;

Pritchard, Jonathan K. .

GENOME BIOLOGY, 2011, 12 (01)

[8] MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1 [J].

Bellacosa, A ;

Cicchillitti, L ;

Schepis, F ;

Riccio, A ;

Yeung, AT ;

Matsumoto, Y ;

Golemis, EA ;

Genuardi, M ;

Neri, G .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (07) :3969-3974

[9] CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[10] Enhanced gene repair mediated by methyl-CpG-modified single-stranded oligonucleotides [J].

Bertoni, Carmen ;

Rustagi, Arjun ;

Rando, Thomas A. .

NUCLEIC ACIDS RESEARCH, 2009, 37 (22) :7468-7482

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