Vasomotor symptoms and accelerated epigenetic aging in the Women's Health Initiative (WHI).
Vasomotor symptoms and accelerated epigenetic aging in the Women's Health Initiative (WHI).
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DOI：
10.1210/clinem/dgaa081
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发表时间：
2020-02
期刊：
影响因子：
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通讯作者：
R. Thurston;J. Carroll;M. Levine;Yuefang Chang;C. Crandall;J. Manson;L. Pal;L. Hou;A. Shadyab-A.-Shad
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文献类型：
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作者：
R. Thurston;J. Carroll;M. Levine;Yuefang Chang;C. Crandall;J. Manson;L. Pal;L. Hou;A. Shadyab-A.-Shad
绝经期的标志性症状，血管紧张症状（VMS），与不良的健康指标有关。然而，VMS和生物老化之间的关系尚未得到验证。我们通过两个基于DNA甲基化的表观遗传衰老指标评估了绝经期VMS和生物衰老之间的关联，这些指标以前与不良的健康结果有关。参与者是妇女健康倡议观察性研究（WHI-OS）整合基因组学子研究（N = 1，206）的成员，他们有两个卵巢，没有接受激素治疗。入组时VMS之间的关系（存在、严重性）或VMS计时组（无VMS：在绝经期开始时和研究入组时均未发生;早期VMS：在绝经期开始时但在入组时未发生;持续性VMS：在绝经期开始时和研究入组时;晚期VMS：在入组时，但不是在绝经期开始时）和预测身体衰老和早期死亡的表观遗传时钟指标在调整年龄、种族/民族、子宫切除术、教育、体重指数、吸烟的线性回归模型中，以及在其他模型中，睡眠障碍中，测试了DNA m表型年龄、DNA m GrimAge）。结果女性平均年龄为65岁。入组时严重潮热与较高的DNAm表型年龄相关[相对于无潮热：B（SE）=2.79（1.27），p= 0.028，多变量]。此外，相对于无VMS，迟发性VMS与较高的DNAm表型年龄[B（SE）=2.15（.84），p=.011]和DNAm GrimAge [B（SE）=1.09（.42），p=.010，多变量]相关。主要结论：在绝经后妇女中，控制实际年龄，重度或迟发性VMS与表观遗传年龄加速相关。绝经后妇女严重或迟发性VMS可能有更大的潜在表观遗传老化。
PURPOSE The hallmark menopausal symptom, vasomotor symptoms (VMS), has been linked to adverse health indicators. However, the relationship between VMS and biological aging has not been tested. We examined associations between menopausal VMS and biological aging as assessed by two DNA methylation-based epigenetic aging indicators previously linked to poor health outcomes. METHODS Participants were members of the Women's Health Initiative Observational Study (WHI-OS) integrative genomics sub-study (N = 1,206) who had both ovaries and were not taking hormone therapy. Relationships between VMS at enrollment (presence, severity) or VMS timing groups (no VMS: not at menopause onset nor at study enrollment; early VMS: at menopause onset but not at enrollment; persistent VMS: at menopause onset and study enrollment; and late VMS: at enrollment but not at menopause onset) and epigenetic clock indicators predictive of physical aging and early death (DNAm PhenoAge, DNAm GrimAge) were tested in linear regression models adjusting for age, race/ethnicity, hysterectomy, education, body mass index, smoking, and in additional models, sleep disturbance. RESULTS Women were on average 65 years of age at enrollment. Severe hot flashes at enrollment were associated with higher DNAm PhenoAge [relative to no hot flashes: B(SE)=2.79(1.27), p=.028, multivariable]. Further, late-occurring VMS were associated with both higher DNAm PhenoAge [B(SE)=2.15 (.84), p=.011] and DNAm GrimAge [B(SE)=1.09 (.42), p=.010, multivariable] relative to no VMS. MAIN CONCLUSIONS Among postmenopausal women, severe or late-occurring VMS was associated with accelerated epigenetic age, controlling for chronological age. Postmenopausal women with severe or late-occurring VMS may have greater underlying epigenetic aging.