Erickson Elise N, Knight Anna K, Smith Alicia K, Myatt Leslie
Midwifery Division, School of Nursing, Oregon Health and Science University, 3455 SW US Veterans Hospital Rd, Portland, OR 97239, USA.
Gynecology & Obstetrics, Emory University, 100 Woodruff Circle, Atlanta, GA 30322, USA.
Epigenetics Commun. 2022;2. doi: 10.1186/s43682-022-00010-0. Epub 2022 May 23.
Advanced maternal age is currently a term defined by chronological age. However, a group of biomarkers known as epigenetic clocks, which can predict morbidity and mortality, has been used to estimate measures of biological aging. Uterine myometrial function during the process of parturition may be influenced by aging, as labor dystocia, unplanned intrapartum cesarean birth, and postpartum hemorrhage are more common in older individuals. The purpose of this study was to evaluate the use of epigenetic clocks in maternal myometrium and blood for predicting age and to evaluate the correlation of epigenetic age between the tissues.
We compared epigenetic age in blood and myometrial samples provided by women undergoing planned cesarean birth at term gestation. Chronological age ranged from 20 to 50 with a median (IQR) age of 35.5(8) years. The MethylationEPIC BeadChip was used to obtain DNA methylation data, and then epigenetic age was calculated using the Horvath, Hannum, GrimAge, and PhenoAge clocks. Spearman correlations of epigenetic age with chronological age were calculated. We tested the relationship of epigenetic age in maternal blood to epigenetic age in myometrium. Age acceleration, for each clock, was also correlated between tissues. Twenty-seven participants provided samples, and 21 matched specimens were included in the final analysis after quality control. Spearman correlation between maternal chronological age and epigenetic age were significant in three of the four clocks (pan-tissue Horvath, Hannum, and GrimAge), for both myometrium and blood samples. Correlations between blood epigenetic age and maternal age ranged from 0.72 to 0.87 (all < 0.001). Correlations between myometrial epigenetic age and maternal age were also significant (0.62-0.70, = 0.002), though lower than correlations seen in blood. Maternal blood epigenetic age also correlated with epigenetic age in myometrium with each of these three clocks 0.60 ( = 0.004, Horvath), 0.63 ( = 0.003, Hannum), and 0.80 ( < 0.001, GrimAge). GrimAge age acceleration had the highest correlation between tissues among the clocks (0.49, = 0.02).
Given the limited sample, this study provides insight into the potential use of epigenetic age derived from blood as a proxy for myometrial epigenetic age, which may be a useful biomarker in estimating myometrial biological age in relationship to myometrial dysfunction. GrimAge outperformed the other tested clocks in terms of concordance of epigenetic age and age acceleration between tissues; however, the Horvath and Hannum clocks may be useful depending on the outcome of interest in pregnancy.
高龄孕产妇目前是一个由实足年龄定义的术语。然而，一组被称为表观遗传时钟的生物标志物可预测发病率和死亡率，已被用于估计生物衰老程度。分娩过程中子宫肌层功能可能受衰老影响，因为产程延长、计划外产时剖宫产和产后出血在高龄产妇中更常见。本研究的目的是评估表观遗传时钟在母体子宫肌层和血液中预测年龄的应用，并评估组织间表观遗传年龄的相关性。
我们比较了足月计划性剖宫产妇女提供的血液和子宫肌层样本中的表观遗传年龄。实足年龄范围为20至50岁，中位（IQR）年龄为35.5（8）岁。使用甲基化EPIC BeadChip获取DNA甲基化数据，然后使用霍瓦斯、汉纳姆、GrimAge和PhenoAge时钟计算表观遗传年龄。计算表观遗传年龄与实足年龄的斯皮尔曼相关性。我们测试了母体血液中的表观遗传年龄与子宫肌层中的表观遗传年龄之间的关系。每个时钟的年龄加速在组织间也具有相关性。27名参与者提供了样本，经过质量控制后，最终分析纳入了21对匹配样本。在四个时钟中的三个（全组织霍瓦斯、汉纳姆和GrimAge）中，母体实足年龄与表观遗传年龄之间的斯皮尔曼相关性在子宫肌层和血液样本中均显著。血液表观遗传年龄与母体年龄之间的相关性范围为0.72至0.87（均<0.001）。子宫肌层表观遗传年龄与母体年龄之间的相关性也显著（0.62 - 0.70，P = 0.002），尽管低于血液中的相关性。母体血液表观遗传年龄与子宫肌层中的表观遗传年龄在这三个时钟中也均具有相关性，分别为0.60（P = 0.004，霍瓦斯）、0.63（P = 0.003，汉纳姆）和0.80（P < 0.001，GrimAge）。在这些时钟中，GrimAge年龄加速在组织间的相关性最高（0.49，P = 0.02）。
鉴于样本有限，本研究深入探讨了将血液中衍生的表观遗传年龄作为子宫肌层表观遗传年龄替代指标的潜在用途，这可能是评估与子宫肌层功能障碍相关的子宫肌层生物学年龄的有用生物标志物。就组织间表观遗传年龄和年龄加速的一致性而言，GrimAge优于其他测试时钟；然而，根据妊娠相关的感兴趣结局，霍瓦斯和汉纳姆时钟可能也有用。
