DNA methylation-based measures of biological age: meta-analysis predicting time to death

被引：728

作者：

Chen, Brian H. ^{[1
,2
,3
]}

Marioni, Riccardo E. ^{[4
,5
,6
]}

Colicino, Elena ^{[7
,8
]}

Peters, Marjolein J. ^{[9
]}

Ward-Caviness, Cavin K. ^{[10
]}

Tsai, Pei-Chien ^{[11
]}

Roetker, Nicholas S. ^{[12
]}

Just, Allan C. ^{[7
,8
]}

Demerath, Ellen W. ^{[12
]}

Guan, Weihua ^{[13
]}

Bressler, Jan ^{[14
]}

Fornage, Myriam ^{[14
,15
]}

Studenski, Stephanie ^{[1
]}

Vandiver, Amy R. ^{[16
]}

Moore, Ann Zenobia ^{[1
]}

Tanaka, Toshiko ^{[1
]}

Kiel, Douglas P. ^{[17
,18
,19
]}

Liang, Liming ^{[20
,21
]}

Vokonas, Pantel ^{[20
]}

Schwartz, Joel ^{[20
]}

Lunetta, Kathryn L. ^{[2
,22
]}

Murabito, Joanne M. ^{[2
,23
]}

Bandinelli, Stefania ^{[24
]}

Hernandez, Dena G. ^{[25
]}

Melzer, David ^{[26
]}

Nalls, Michael ^{[25
]}

Pilling, Luke C. ^{[26
]}

Price, Timothy R. ^{[25
]}

Singleton, Andrew B. ^{[25
]}

Gieger, Christian ^{[10
,27
]}

Holle, Rolf ^{[28
]}

Kretschmer, Anja ^{[10
,27
]}

Kronenberg, Florian ^{[29
]}

Kunze, Sonja ^{[10
,27
]}

Linseisen, Jakob ^{[10
]}

Meisinger, Christine ^{[10
]}

Rathmann, Wolfgang ^{[30
]}

Waldenberger, Melanie ^{[10
,27
]}

Visscher, Peter M. ^{[4
,6
,31
]}

Shah, Sonia ^{[6
,31
]}

Wray, Naomi R. ^{[6
]}

McRae, Allan F. ^{[6
,31
]}

Franco, Oscar H. ^{[32
]}

Hofman, Albert ^{[20
,32
]}

Uitterlinden, Andre G. ^{[9
,32
]}

Absher, Devin ^{[33
]}

Assimes, Themistocles ^{[34
]}

Levine, Morgan E. ^{[35
]}

Lu, Ake T. ^{[35
]}

Tsao, Philip S. ^{[34
,36
]}

机构：

[1] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA

[2] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA

[3] NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD 01702 USA

[4] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland

[5] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH4 2XU, Midlothian, Scotland

[6] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[7] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, Lab Environm Epigenet, New York, NY 10032 USA

[8] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, Lab Environm Epigenet, New York, NY 10032 USA

[9] Erasmus Univ, Med Ctr, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands

[10] Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany

[11] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England

[12] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA

[13] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA

[14] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA

[15] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[16] Johns Hopkins Univ, Ctr Epigenet, Baltimore, MD 21205 USA

[17] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA

[18] Harvard Med Sch, Boston, MA USA

[19] Hebrew Senior Life, Inst Aging Res, Boston, MA 02215 USA

[20] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[21] Harvard Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[22] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA

[23] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02118 USA

[24] Usl Ctr Toscana, Geriatr Unit, Florence, Italy

[25] NIA, Lab Neurogenet, Intramural Res Program, NIH, Bethesda, MD 20814 USA

[26] Univ Exeter, Sch Med, Epidemiol & Publ Hlth, Exeter EX2 5DW, Devon, England

[27] Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany

[28] Helmholtz Zentrum Munchen, Inst Hlth Econ & Hlth Care Management, D-85764 Neuherberg, Germany

[29] Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, A-6020 Innsbruck, Austria

[30] Heinrich Heine Univ, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, D-40225 Dusseldorf, Germany

[31] Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia

[32] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands

[33] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA

[34] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA

[35] Univ Calif Los Angeles, David Geffen Sch Med, Human Genet, Los Angeles, CA 90095 USA

[36] VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA

[37] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA

[38] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA

[39] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA

[40] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA

[41] George Washington Univ, Childrens Natl Med Ctr, Ctr Translat Sci, Washington, DC 20010 USA

[42] Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA

[43] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA

[44] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA

[45] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[46] Johns Hopkins Univ, Sch Med, Dept Mol Biol Genet, Baltimore, MD 21205 USA

[47] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[48] Johns Hopkins Univ, Sch Med, Dept Biostat, Baltimore, MD 21205 USA

[49] NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA

[50] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA

来源：

AGING-US | 2016年 / 8卷 / 09期

关键词：

all-cause mortality; lifespan; epigenetics; epigenetic clock; DNA methylation; mortality; ALL-CAUSE MORTALITY; EPIGENETIC CLOCK; DISEASE; BLOOD; COHORT; EPIDEMIOLOGY; CANCER; BRAIN; LIFE;

D O I：

10.18632/aging.101020

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Estimates of biological age based on DNA methylation patterns, often referred to as "epigenetic age", "DNAm age", have been shown to be robust biomarkers of age in humans. We previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, we examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality. All considered measures of epigenetic age acceleration were predictive of mortality (p <= 8.2x10(-9)), independent of chronological age, even after adjusting for additional risk factors (p<5.4x10(-4)), and within the racial/ethnic groups that we examined (non-Hispanic whites, Hispanics, African Americans). Epigenetic age estimates that incorporated information on blood cell composition led to the smallest p-values for time to death (p=7.5x10(-43)). Overall, this study a) strengthens the evidence that epigenetic age predicts all-cause mortality above and beyond chronological age and traditional risk factors, and b) demonstrates that epigenetic age estimates that incorporate information on blood cell counts lead to highly significant associations with all-cause mortality.

引用

页码：1844 / 1865

页数：22

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