Socioenvironmental Causes of Elevated Toxic Metal Levels and Epigenetic Aging

项目总结： 减少人类接触有毒金属是国家和全球公共卫生优先事项。暴露在空气中的风险 有毒金属在美国各地分布不均，接触许多金属的负担要高得多 工业污染物在人口稠密的城市地区社会经济地位较低的个人和 少数族裔。尽管个人特征之间的联系(社会经济地位、职业、获得 净水等。)有毒金属含量升高的生物标记物此前已被确定，但很少有研究 调查了大规模社会、经济和环境变化对血清金属水平的影响。vt.给出 由于工业活动和去工业化，许多美国城市地区的快速变化，理解 城市工业环境污染和邻里社会环境带来的人口风险 为了减轻有毒金属对人口健康的影响，改变势在必行。 这项建议的目标是(1)描述城市社会环境变化对 单独和联合血清铅(铅)、汞(汞)、铬(铬)和锰(锰)，以及(2)评估 铅、汞、铬、锰对表观遗传衰老的单独和同时作用。779年的纵向数据 2008-2013年底特律社区健康研究(DNHS)的参与者和特定地点城市的数据 来自美国社区调查的环境污染物，密歇根州环境质量部， 密歇根州交通部将用来评估街区群建筑质量的影响， 空置房屋、棕地污染和商业交通密度对血清铅、汞、 Cr和mN。DNA甲基化分析产生的表观遗传年龄的纵向测量将用于 评估铅、汞、铬和锰对生物加速老化的单独和联合影响。完成 建议的目标将大大促进我们对城市金属暴露负担的理解。 美国，以及它们对表观遗传衰老的个体和联合影响，是所有原因的准确预测因素 死亡率。DNHS提供了一个很好的机会，可以使用纵向数据进行拟议的研究 来自一个正在进行重大重建的高度工业化城市的具有代表性的成年人样本。 这份F30提案中概述的培训计划将使申请者具备必要的社交技能， 环境、表观遗传学、流行病学和临床医学，以圆满完成拟议目标 作为一名研究社会劣势和社会劣势相互关联影响的内科科学家 美国环境污染对人口健康的影响。申请者得到了极好的支持 由流行病学家、毒物学家、环境科学家、地理学家和 具有必要专业知识的临床医生，以支持他的临床培训和博士研究。

Project Summary: Reducing human exposure to toxic metals is a national and global public health priority. The risk of exposure to toxic metals is unevenly distributed across the United States, with a much higher burden of exposure to many industrial pollutants in densely populated urban areas among individuals of lower socioeconomic position and minority race. Although links between individual characteristics (socioeconomic position, occupation, access to clean water, etc.) and biomarkers of elevated toxic metals have been previously established, few studies have investigated the effect of large-scale social, economic, and environmental changes on serum metal levels. Given rapid changes in many American urban areas due to industrial activity and deindustrialization, understanding the population-level risks posed by urban industrial environmental pollution and neighborhood socioenvironmental change is imperative to mitigate the effects of toxic metals on population health. The objectives of this proposal are to (1) characterize the effects of urban socioenvironmental changes on individual and joint serum lead (Pb), mercury (Hg), chromium (Cr), and manganese (Mn), and (2) assess the individual and simultaneous effects of Pb, Hg, Cr, and Mn on epigenetic aging. Longitudinal data from 779 participants in the 2008-2013 Detroit Neighborhood Health Study (DNHS) and data on location-specific urban environmental pollutants from the American Community Survey, Michigan Department of Environmental Quality, and Michigan Department of Transportation will be used to assess the effects of block group building quality, vacant housing, brownfield pollution, and commercial traffic density on longitudinal measures of serum Pb, Hg, Cr, and Mn. Longitudinal measures of epigenetic age generated from DNA methylation analysis will be used to assess the individual and joint effects of Pb, Hg, Cr, and Mn on accelerated biological aging. The completion of the proposed aims will significantly advance our understanding of the burden of metal exposures in urban America, as well as their individual and joint effects on epigenetic aging, an accurate predictor of all-cause mortality. The DNHS provides an excellent opportunity to conduct the proposed research using longitudinal data from a representative sample of adults in a heavily industrialized city undergoing significant redevelopment. The training plan outlined in this F30 proposal will equip the applicant with the necessary skills in social, environmental, and epigenetic epidemiology and clinical medicine to successfully complete the proposed aims and progress into a role as a physician-scientist studying the interrelated effects of social disadvantage and environmental pollution on population health in the United States. The applicant is extremely well supported by an interdisciplinary group of epidemiologists, toxicologists, environmental scientists, geographers, and clinicians with the requisite expertise to support his clinical training and doctoral research.