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

黑人女性的表观遗传衰老、社会因素和早产

• 批准号: 10605694
• 负责人: Carmen Giurgescu
• 金额: $ 73.19万
• 依托单位: UNIVERSITY OF CENTRAL FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-18 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10605694
• 关键词: 37 weeks gestation; Acceleration; Address; Age; Age Years; Aging; Area; Biological; Biological Aging; Biological Markers; Birth; Black Populations; Black race; Blood; Blood specimen; COVID-19 pandemic; Cell Aging; Chronic stress; Chronology; Coupled; Crime; DNA; DNA Methylation; Data; Disease; Enrollment; Epigenetic Process; Genetic; Gestational Age; Goals; Individual; Individual Differences; Infant; Infant Mortality; Length; Life Experience; Maternal Age; Measures; Medical Records; Methylation; Neighborhoods; Not Hispanic or Latino; Participant; Pattern; Performance; Precision Health; Pregnancy; Pregnant Women; Premature Birth; Prevention; Publishing; Questionnaires; Race; Reporting; Research; Ribosomal DNA; Ribosomes; Risk; Risk Assessment; Risk Factors; Saliva; Sampling; Shapes; Term Birth; Weather; Whole Blood; Woman; Work; age related; bisulfite sequencing; black men; black women; case control; cohort; design; driving force; experience; high risk; inter-individual variation; metropolitan; neighborhood disadvantage; novel; prevent; racial discrimination; racism; social factors; social stressor; systematic review; telomere; therapeutic target

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.

项目摘要 早产（PTB；妊娠<37周）是黑人婴儿死亡的主要原因。 母亲的实际年龄长期以来一直被用来评估 PTB 的风险。 假设个体以相似的速度衰老，并且没有捕捉到个体间的差异 尽管黑人和白人女性的产妇年龄都有所增加，但可能因种族而存在。 PTB，在所有孕产妇年龄中，黑人女性患 PTB 的风险均高于白人女性。 Geronimus 的风化假说描述了一种模式，其中 PTB 与年龄相关的增加发生在 黑人女性的年龄较小，风险随年龄增长呈线性模式，而不是 J- 总体上与实际年龄形成关联。 由于种族的社会压力，黑人女性更有可能承受慢性压力 歧视、邻里混乱和犯罪。 生物老化，反映了过去暴露的影响，可能更有助于确定风险 PTB 与实际年龄相比，无论生活经历如何，实际年龄都是一致的。 缺乏（1）社会压力源与黑人孕妇表观遗传衰老之间的关联； (2) 这些女性中表观遗传衰老与 PTB 的关联。 弥补先前研究中的空白，并依靠我们先前的工作证明核糖体 DNA 甲基化 (rDNAm) 包含 rDNA 时钟，这是一种新颖、灵敏且进化保守的时钟。 本研究的目的是检查表观遗传衰老作为社会压力源的标志。 我们的队列由 550 名黑人组成。 在 COVID-19 大流行之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 Giurgescu） 妇女填写了问卷并提供了全血。 怀孕期间的样本和唾液，这些生物样本将用于完成 拟议的研究已被提取。我们的目标是：（目标 1）确定。 社会压力源是否与黑人孕妇的 rDNAm 时钟加速有关 （目标 2）确定患有 PTB 的女性是否具有比 足月分娩的妇女；以及（目标 3）评估与 PTB 相关的 rDNAm 时钟的性能 相对于表观遗传衰老的替代指标，表观遗传年龄是相互间的生物学反映。 衰老的个体差异具有作为预防 PTB 的有用参数的巨大潜力 目前，预测 PTB 的能力很差，尤其是黑人。 精准健康有可能识别出有患 PTB 风险的女性个体，并 确定预防个体患 PTB 的治疗靶点。