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: 9890792
• 负责人: Margaret Takako Hicken
• 金额: $ 76.06万
• 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/9890792
• 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 disadvantage; social stressor; 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.

摘要 健康老龄化中的种族不平等已经有了很好的记录。与美国白人相比，黑人 美国人在很小的时候就会经历疾病和死亡，并表现出与年龄相关的健康下降幅度更大。我们的 社区，作为我们生活、学习、玩耍和祈祷的场所，可能是这些东西的强大来源 种族不平等。种族居住隔离(这是将不同的种族群体分成不同的 通过历史和当前的歧视性政策和做法)造成了种族上的 不平等的美国社区景观。黑人居多的社区经历更多 贫穷、公民和商业撤资，以及更多暴露在环境危害中 以白人居民为主的社区。当更多的研究人员记录下 在健康不平等的社区，我们实际上可能低估了社区的真正影响 背景，因为我们经常关注特定的健康结果，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，导致了许多此类疾病-- 其中一种机制可能是改变我们的基因组结构，称为表观基因组学。而我们的基因 不是改变，环境可能会影响我们的基因是否真的得到了“表达”。我们会 确定在种族隔离的社区中积累的成年生活经验是否 与被称为DNA甲基化的表观基因组模式相关。我们还将具体确定是否 成年人接触邻里工业空气污染的累积和危害一起 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 我们看到的是与健康老龄化中的种族不平等有关。我们假设种族隔离的黑人 工业空气污染水平更高、社会劣势更大的社区将与 DNA甲基化模式的类型已被证明与慢性疾病在分子上有关 学习。事实上，我们进一步假设，DNA甲基化的这些模式将与种族有关 认知功能的不平等和患慢性病的数量。澄清企业的角色 健康老龄化中种族不平等的邻里环境至关重要，因为邻里并不自然- 发生的。它们通过政策发展和变化，并容易受到干预。确定的角色 DNA甲基化可能是许多慢性病的基础，这将澄清社区和 指出潜在的有效干预措施。