TY - JOUR
T1 - Menopause accelerates biological aging
AU - Levine, Morgan E.
AU - Lu, Ake T.
AU - Chen, Brian H.
AU - Hernandez, Dena G.
AU - Singleton, Andrew B.
AU - Ferrucci, Luigi
AU - Bandinelli, Stefania
AU - Salfati, Elias
AU - Manson, Jo Ann E
AU - Quach, Austin
AU - Kusters, Cynthia D J
AU - Kuhi, Diana
AU - Wong, Andrew
AU - Teschendorff, Andrew E.
AU - Widschwendter, Martin
AU - Ritz, Beate R.
AU - Absher, Devin
AU - Assimes, Themistocles L.
AU - Horvath, Steve
PY - 2016/8/16
Y1 - 2016/8/16
N2 - 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 womenwho underwentmenopausal 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 studieswill be needed to dissect cause-and-effect relationships further.
AB - 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 womenwho underwentmenopausal 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 studieswill be needed to dissect cause-and-effect relationships further.
KW - Aging
KW - DNA methylation
KW - Epigenetic clock
KW - Menopause
KW - WHI
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U2 - 10.1073/pnas.1604558113/-/DCSupplemental
DO - 10.1073/pnas.1604558113/-/DCSupplemental
M3 - Article
SN - 0027-8424
VL - 113
SP - 9327
EP - 9332
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 33
ER -