Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2016 Aug 16;113(33):9327-32. doi: 10.1073/pnas.1604558113. Epub 2016 Jul 25.

Menopause accelerates biological aging.

Author information

1
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; Center for Neurobehavioral Genetics, University of California, Los Angeles, CA 90095;
2
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095;
3
Longitudinal Studies Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892;
4
Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892;
5
Geriatric Unit, Azienda Sanitaria di Firenze, 50100; Florence, Italy;
6
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305;
7
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
8
Department of Epidemiology, School of Public Health, University of California, Los Angeles, CA 90095;
9
Medical Research Council Unit for Lifelong Health and Ageing, University College London, London WC1B 5JU, United Kingdom;
10
Department of Women's Cancer, University College London, London WC1 6BT, United Kingdom; University College London Cancer Institute, University College London, London WC1 6BT, United Kingdom; Statistical Genomics Group, University College London Cancer Institute, University College London, London WC1E 6DD, United Kingdom; Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Society Partner Institute for Computational Biology, Chinese Academy of Sciences, Shanghai Institute for Biology, Shanghai 200031, China;
11
Department of Women's Cancer, University College London, London WC1 6BT, United Kingdom;
12
HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806;
13
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA 90095 shorvath@mednet.ucla.edu.

Abstract

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); Invecchiare 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.

KEYWORDS:

DNA methylation; WHI; aging; epigenetic clock; menopause

PMID:
27457926
PMCID:
PMC4995944
DOI:
10.1073/pnas.1604558113
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center