Epigenetic aging, social factors, and preterm birth among Black women

项目摘要 早产(妊娠37周)是黑人婴儿死亡的主要原因。 母亲的时序年龄长期以来一直被用来评估肺结核的风险；然而，时序年龄 假设个体以相似的速度老化，并且没有捕捉到个体之间的差异 可能因为种族而存在。尽管黑人和白人妇女都有与母亲年龄相关的增加 在所有产妇年龄段，黑人妇女患肺结核的风险都高于白人妇女。 Geronimus的风化假说描述了一种模式，即与年龄相关的肺结核增加发生在 黑人女性的年龄越小，风险随着年龄的增长而线性增加，而不是J- 总体上形成了与实际年龄的联系。老龄化的加速被归因于 黑人女性更有可能因种族的社会压力而经历慢性压力 歧视、邻里骚乱和犯罪。表观遗传年龄，一种衡量细胞或 生物老化，反映了过去暴露的影响，在确定心脏病风险方面可能更有用 PTB高于按时间顺序排列的年龄，后者与生活经历无关，都是一致的。然而，研究表明 缺乏(1)社会应激源与黑人孕妇表观遗传衰老的关系； 以及(2)这些女性中表观遗传老化与肺结核的关系。这项研究旨在 解决先前研究中的空白，并依赖于我们之前的工作证明核糖体DNA 甲基化(RDNAm)含有rDNA时钟，这是一种新的、敏感的和进化上保守的时钟 表观遗传衰老。这项研究的目的是检验表观遗传衰老作为社会压力来源的标志。 以及一个指示黑人女性患肺结核风险的生物标记物。我们的队伍由550名黑人组成 新冠肺炎大流行前从密歇根州底特律和俄亥俄州哥伦布登记的孕妇 地区(R01 MD011575，Pi Giurescu)。妇女填写调查问卷并提供全血 样本和唾液，这些生物样本将被用来完成 建议的研究。产妇的医疗记录已被摘录。我们的目标是：(目标1)确定 社会应激源是否与黑人孕妇rDNAm时钟加快有关 女性；(目标2)确定患有肺结核的女性是否有比较快的rDNA时钟 和(目标3)评估与肺结核相关的rDNAm时钟的表现 相对于表观遗传老化的替代指标。表观遗传年龄，从生物学角度反映了 个体变异性在老龄化中具有显著的潜力，可以作为结核病预防的有用参数 精准的健康视角。目前，预测肺结核的能力很差，特别是在黑人中 女人。精确的健康状况有可能识别出有肺结核风险的个别女性，并 确定治疗目标，以防止个人患上肺结核。

PROJECT ABSTRACT Preterm birth (PTB; <37 weeks gestation) is the leading cause of infant mortality among Black infants. Maternal chronological age has long been used to assess risk for PTB; however, chronological age assumes that individuals age at similar rates and does not capture the inter-individual differences that may exist due to race. Although both Black and White women have a maternal age-related increase in PTB, the risk for PTB is higher among Black women than among White women at all maternal ages. Geronimus’ weathering hypothesis describes a pattern in which age-related increases in PTB occur at a younger age for Black women, and risk with age increases in a linear pattern, rather than the J- shaped association with chronological age overall. This acceleration of aging has been attributed to Black women being more likely to experience chronic stress due to social stressors of racial discrimination and neighborhood disorder and crime. Epigenetic age, a measure of cellular or biological aging, reflects influences of past exposures and may be more useful in determining risk for PTB than chronological age, which is uniform regardless of life experiences. However, research is lacking on (1) the association of social stressors with epigenetic aging among Black pregnant women; and (2) the association of epigenetic aging with PTB among these women. This study is designed to address the gaps in prior research and relies on our previous work demonstrating that ribosomal DNA methylation (rDNAm) harbors the rDNA clock, a novel, sensitive, and evolutionarily conserved clock of epigenetic aging. The goal of this study is to examine epigenetic aging as a marker of social stressors and a biomarker indicating risk of PTB among Black women. Our cohort is comprised of 550 Black pregnant women enrolled prior to the COVID-19 pandemic from the Detroit, MI and Columbus, OH areas (R01 MD011575, PI Giurgescu). Women completed questionnaires and provided whole blood samples and saliva during pregnancy, and these biological samples will be used to complete the proposed study. Maternal medical records have been abstracted. We aim to: (Aim 1) Determine whether social stressors are associated with an accelerated rDNAm clock among Black pregnant women; (Aim 2) Determine whether women with PTB have an accelerated rDNAm clock compared with women with term birth; and (Aim 3) Assess performance of the rDNAm clock associated with PTB relative to alternative metrics of epigenetic aging. Epigenetic age, a biological reflection of inter- individual variability in aging, holds significant potential as a useful parameter in PTB prevention from a precision health perspective. Currently, the ability to predict PTB is poor, especially among Black women. Precision health has the potential to identify individual women who are at risk for PTB, and to identify therapeutic targets to prevent an individual from having PTB.