期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 33, 页码 9327-9332出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1604558113
关键词
menopause; DNA methylation; aging; WHI; epigenetic clock
资金
- NIH/NHLBI Grant [60442456 BAA23]
- NIH/National Institute on Aging Grant [1U34AG051425-01]
- NIH/National Institute of Neurological Disorders and Stroke Grant [T32NS048004]
- NHLBI of the NIH, US Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]
- Eve Appeal
- Department of Health National Institute for Health Research Biomedical Research Centres funding scheme
- UK Medical Research Council Grant [MC_UU_12019/1]
- NIH/National Institute of Environmental Health Sciences Grants [R21-ES024356, R01-ES10544]
- MRC [MC_UU_12019/1] Funding Source: UKRI
- Medical Research Council [MC_UU_12019/1] Funding Source: researchfish
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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