Menopause accelerates biological aging

被引：301
|
作者：
Levine, Morgan E. [1 ,2 ]
Lu, Ake T. [1 ]
Chen, Brian H. [3 ]
Hernandez, Dena G. [4 ]
Singleton, Andrew B. [4 ]
Ferrucci, Luigi [3 ]
Bandinelli, Stefania [5 ]
Salfati, Elias [6 ]
Manson, JoAnn E. [7 ]
Quach, Austin [1 ]
Kusters, Cynthia D. J. [8 ]
Kuh, Diana [9 ]
Wong, Andrew [9 ]
Teschendorff, Andrew E. [10 ,11 ,12 ,13 ]
Widschwendter, Martin [10 ]
Ritz, Beate R. [8 ]
Absher, Devin [14 ]
Assimes, Themistocles L. [6 ]
Horvath, Steve [1 ,15 ]
机构：
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA
[3] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA
[4] NIA, Lab Neurogenet, Intramural Res Program, NIH, Bethesda, MD 20892 USA
[5] Azienda Sanit Firenze, Geriatr Unit, I-50100 Florence, Italy
[6] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA
[7] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[8] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA
[9] UCL, Unit Lifelong Hlth & Ageing, Med Res Council, London WC1B 5JU, England
[10] UCL, Dept Womens Canc, London WC1 6BT, England
[11] UCL, Inst Canc, London WC1 6BT, England
[12] UCL, Inst Canc, Stat Genom Grp, London WC1E 6DD, England
[13] Chinese Acad Sci, Shanghai Inst Biol, Chinese Acad Sci Max Planck Soc Partner Inst Comp, Key Lab Computat Biol, Shanghai 200031, Peoples R China
[14] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA
[15] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2016年 / 113卷 / 33期
基金：
英国医学研究理事会;
关键词：
menopause; DNA methylation; aging; WHI; epigenetic clock; DNA METHYLATION AGE; EPIGENETIC AGE; PARKINSONS-DISEASE; BLOOD; MORTALITY; EPIDEMIOLOGY; HERITABILITY; ASSOCIATION; ABILITY; CELLS;
D O I：
10.1073/pnas.1604558113
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the "epigenetic clock"), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invec-chiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further.
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页码：9327 / 9332
页数：6
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