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据可查。与白色美国人相比， 美国人在很小的时候就经历了疾病和死亡，并且在健康方面表现出与年龄相关的急剧下降。我们 社区作为我们生活、学习、娱乐和祈祷的场所，可能是这些信息的有力来源。 种族不平等种族居住隔离（将不同的种族群体分为不同的种族）。 社区通过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经历更多 贫困，公民和商业撤资，以及与环境危害相比， 居民多为白色的社区。虽然越来越多的研究人员正在记录 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， 这是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，体内可能有共同的生物学机制驱动许多这些疾病- 其中一个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 虽然环境不会改变，但环境会影响我们的基因是否真的“表达”。我们将 确定在种族隔离的社区中成年生活经验的积累是否 与表观基因组模式DNA甲基化有关。我们还将具体确定 成年期暴露于邻近工业空气污染的累积和不利条件一起， 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 与健康老龄化中的种族不平等有关。我们假设种族隔离黑人 社区，其工业空气污染和社会劣势的水平更高，将与 DNA甲基化的模式类型已被证明与分子生物学中的慢性疾病有关， 问题研究事实上，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一个人患有的慢性疾病的数量。澄清联合国的作用 健康老龄化中种族不平等的邻里环境至关重要，因为邻里关系并不自然- 正在发生。它们通过政策而发展和变化，并接受干预。确定下列人员的作用 DNA甲基化可能是许多慢性疾病的基础，它将阐明邻里关系的重要性， 指出潜在的有效干预措施。