Racial inequalities in health throughout adulthood: The cumulative impact of neighborhood chemical and non-chemical stressors on epigenomic pathways

整个成年期健康方面的种族不平等：邻里化学和非化学压力源对表观基因组途径的累积影响

• 批准号: 9763639
• 负责人: Margaret Takako Hicken
• 金额: $ 71.68万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-14 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9763639
• 关键词: Acceleration; Adult; African American; Age; Aging; Air Pollution; American; Biological; Blood; Cardiovascular Diseases; Cessation of life; Chemicals; Chronic; Chronic Disease; Collection; Complex; DNA; DNA Markers; DNA Methylation; Data; Data Collection; Data Set; Development; Diabetes Mellitus; Disadvantaged; Disease; Ecology; Environment; Environmental Hazards; Environmental Pollution; Epigenetic Process; Etiology; Exposure to; Genes; Health; Immune; Industrialization; Inequality; Intervention; Learning; Link; Literature; Measures; Methylation; Modeling; Molecular; Morbidity - disease rate; Neighborhoods; Outcome; Pathway interactions; Pattern; Physical environment; Play; Policies; Population; Poverty; Race; Research; Research Personnel; Role; Site; Social Environment; Social Sciences; Sorting - Cell Movement; Source; Stress; System; age related; caucasian American; cognitive function; effective intervention; epigenomics; experience; health inequalities; healthy aging; methylation pattern; mortality; response; segregation; social; stressor; structural genomics

ABSTRACT Racial inequalities in healthy aging have been well-documented. Compared to White Americans, Black Americans experience illness and death at early ages and show steeper age-related declines in health. Our neighborhoods, as the site of where we live, learn, play, and pray, may serve as a powerful source of these racial inequalities. Racial residential segregation (which is the sorting of different racial groups into different neighborhoods through historical and current discriminatory policies and practices) has resulted in a racially unequal American neighborhood landscape. Neighborhoods with mostly Black residents experience more poverty, civic and commercial disinvestment, and more exposure to environmental hazards compared to neighborhoods with mostly White residents. While more researchers are documenting the role of neighborhoods in health inequalities, we may actually be underestimating the true impact of neighborhood context, because we often focus on specific health outcomes, such as cardiovascular disease or diabetes. However, there are likely shared biological mechanisms within the body that drive many of these diseases – and one such mechanism may be changes to our genomic structure, called epigenomics. While our genes do not change, the environment can have an impact on whether our genes are actually “expressed”. We will determine whether the accumulation of adulthood lived experience in racially-segregated neighborhoods is related to epigenomic patterns called DNA methylation. We will also specifically determine whether the accumulation of adulthood exposure to neighborhood industrial air pollution and disadvantage together are related to these patterns of DNA methylation. Finally, we will determine whether the DNA methylation patterns we see are related to racial inequalities in healthy aging. We hypothesize that racially-segregation Black neighborhoods, with their greater levels of industrial air pollution and social disadvantage, will be related to the types of patterns in DNA methylation that have been shown to be related to chronic diseases in molecular studies. In fact, we further hypothesize that these patterns in DNA methylation will be related to racial inequalities in cognitive function and the number of chronic diseases one has had. Clarifying the role of neighborhood context in racial inequalities in healthy aging is critical, as neighborhoods are not naturally- occurring. They develop and change through policies and are amenable to intervention. Identifying the role of DNA methylation that likely underlies many chronic diseases, will clarify the importance of neighborhoods and point to potential effective interventions.

抽象的 健康老龄化方面的种族不平等已有充分记录。与美国白人相比，黑人 美国人在很小的时候就经历过疾病和死亡，并且与年龄相关的健康状况出现更严重的下降。我们的 社区作为我们生活、学习、玩耍和祈祷的场所，可能是这些信息的强大来源。 种族不平等。种族居住隔离（将不同种族群体分为不同的居住区） 历史和当前的歧视性政策和做法）导致了种族歧视 不平等的美国社区景观。以黑人居民为主的社区体验更多 与其他国家相比，贫困、公民和商业投资减少以及更多地面临环境危害 以白人居民为主的社区。虽然越来越多的研究人员正在记录其作用 社区的健康不平等，我们实际上可能低估了社区的真正影响 因为我们经常关注特定的健康结果，例如心血管疾病或糖尿病。 然而，体内可能存在共同的生物机制来驱动许多这些疾病—— 其中一种机制可能是我们的基因组结构的变化，称为表观基因组学。虽然我们的基因确实如此 环境不会改变，但它会影响我们的基因是否真正“表达”。我们将 确定在种族隔离社区中成年生活经验的积累是否 与称为 DNA 甲基化的表观基因组模式有关。我们还将具体确定是否 成年后暴露于附近工业空气污染和不利条件的累积是 与这些 DNA 甲基化模式有关。最后，我们将确定DNA甲基化模式是否 我们看到这与健康老龄化方面的种族不平等有关。我们假设种族隔离黑人 工业空气污染程度较高且社会地位较差的社区将与 DNA 甲基化模式类型已被证明与分子生物学中的慢性疾病相关 研究。事实上，我们进一步假设 DNA 甲基化的这些模式与种族有关 认知功能的不平等和人们患有的慢性疾病的数量。明确角色 健康老龄化过程中种族不平等的邻里环境至关重要，因为邻里并不自然地- 发生。它们通过政策发展和变化，并且愿意接受干预。确定角色 DNA 甲基化可能是许多慢性疾病的根源，这将阐明社区和社区的重要性 指出潜在的有效干预措施。