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。 长期以来，母亲的实际年龄一直被用来评估PTB的风险;然而，实际年龄 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， 可能是因为种族。尽管黑人和白色女性的生育率都有与年龄相关的增加， PTB，在所有产妇年龄，黑人妇女患PTB的风险高于白色妇女。 Geronimus的风化假说描述了一种模式，其中与年龄相关的PTB增加发生在 黑人女性的年龄更小，风险随着年龄的增长呈线性增长，而不是J- 与整体实足年龄的关系。这种加速老化的现象被归因于 黑人女性更容易因种族歧视的社会压力而经历慢性压力 歧视、邻里混乱和犯罪。表观遗传年龄是衡量细胞或 生物老化，反映了过去暴露的影响，可能更有助于确定 PTB比实足年龄，这是统一的，无论生活经历。然而，研究 缺乏（1）社会压力与黑人孕妇表观遗传衰老的关联; （2）表观遗传衰老与PTB的关系。本研究旨在 填补了先前研究的空白，并依赖于我们先前的工作，证明核糖体DNA 甲基化（rDNAm）携带rDNA时钟，一种新的，敏感的，进化上保守的时钟。 表观遗传老化本研究的目的是检验表观遗传衰老作为社会压力源的一个标志 和一种生物标志物，表明黑人妇女患肺结核的风险。我们的队伍由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 区域（R 01 MD 011575，PI Giescu）。女性完成问卷并提供全血 这些生物样本将用于完成 建议的研究。产妇的医疗记录已经被提取出来了。我们的目标是：（目标1）确定 社会压力是否与黑人孕妇rDNAm时钟加速有关 女性;（目的2）确定PTB女性是否具有加速的rDNAm时钟， （目的3）评估与PTB相关的rDNAm时钟的性能 相对于表观遗传老化的替代指标。表观遗传年龄，一个生物学上的反映， 在老化中的个体差异，作为预防PTB的有用参数， 精准健康视角目前，预测PTB的能力很差，特别是在黑人中 妇女精确的健康有可能识别出有PTB风险的个体女性， 确定治疗靶点以预防个体患有PTB。