Impact of Metals on Biological Aging and Cardiometabolic Traits in Adolescents

摘要 环境中无处不在的有毒金属暴露是一个全球公共卫生问题， 处境不利的人群极易受到不利影响的影响。铅，砷， 镉和汞是环境中最常见的有毒金属暴露。 人口。这些金属暴露在有毒物质和疾病机构的前7名之列 登记物质优先列表，根据物质的使用频率、毒性和 有可能暴露在人体内。人口研究的观察结果支持这些金属之间的联系 成年期暴露与心血管疾病；然而，有关早期生活的文献很少。 影响心脏新陈代谢的健康。对儿童心血管疾病起源的研究表明，早期 生活因素影响一生中的心血管风险，青春期是发育的敏感期 环境保护 诱发生物衰老的因素，如支持的改变 这些是理解早期接触金属如何影响心脏代谢健康的机制。 建立心脏代谢表型轨迹的时期。有新的证据表明 DNA甲基化和端粒长度，因此 解决当前科学文献中的差距将改善暴露、补救和降低风险 在最脆弱的人群中制定战略，并为新的疾病预防机会提供支持。 拟议的流行病学研究将为(1)金属对早期健康的影响提供见解。 暴露，(2)金属联合暴露的影响，(3)青春期是心脏代谢的敏感期 表型编程，以及(4)金属暴露引起心脏代谢的作用机制 功能障碍。这项研究的总体目标是评估金属联合暴露对心脏代谢特征的影响 青春期的轨迹和生物衰老。我们将利用现有的孟加拉国 儿童健康环境研究(BIRCH)队列，由500名居住在农村的青年组成 孟加拉。登记的参与者将在拟议的第一次研究访问时年龄在11至13岁之间。 我们提出了以下具体目标：(1)评估金属暴露与纵向 青春期心脏代谢特征；(2)评估金属暴露与 青春期DNA甲基化与DNA甲基化年龄；(3)评价金属的关联性 在青春期暴露与白细胞端粒长度的变化。拟议的流行病学 青春期的研究将提供新的数据来揭示金属暴露对心血管的影响 疾病的发病机制在非常早期阶段。这项研究可能会为DNA甲基化和 端粒长度作为金属暴露的生物传感器，在未来的研究中用于识别高危个体 心脏代谢功能障碍和其他相关不良健康后果。

ABSTRACT The ubiquitous presence of toxic metal exposures in the environment is a global public health concern, with disadvantaged populations disproportionately exposed and susceptible to adverse effects. Lead, arsenic, cadmium, and mercury are the most commonly occurring toxic environmental metal exposures in the general population. These metal exposures appear among the top 7 of the Agency for Toxic Substances and Disease Registry Substance Priority List, prioritizing substances based on a combination of their frequency, toxicity, and potential for human exposure. Observations from population studies support associations between these metal exposures and cardiovascular diseases in adulthood; however, the literature is sparse for early life cardiometabolic health impacts. Research on the childhood origins of cardiovascular diseases shows that early life factors influence cardiovascular risk over the life course, with adolescence a sensitive developmental environmental factors eliciting biological aging, such as alterations to supporting these as mechanisms for understanding how early life metal exposures can affect cardiometabolic health. period for establishing cardiometabolic phenotype trajectories. There is emerging evidence of DNA methylation and telomere length, thus Addressing gaps in the current scientific literature will improve exposure remediation and risk reduction strategies in the most vulnerable populations and provide support for new disease prevention opportunities. The proposed epidemiologic research will provide insights on the (1) early-life health effects of metal exposures, (2) impacts of metal co-exposures, (3) adolescence as a sensitive period for cardiometabolic phenotype programming, and (4) mechanisms of action by which metal exposures cause cardiometabolic dysfunction. This study's overall goal is to evaluate the effect of metal co-exposures on cardiometabolic trait trajectories and biological aging during adolescence. We will leverage the established Bangladesh Environmental Research in Children's Health (BiRCH) cohort, comprised of 500 youth residing in rural Bangladesh. Enrolled participants will be aged 11 to 13 years at the time of the proposed first research visit. We propose the following specific aims: (1) to evaluate the association of metal exposures with longitudinal cardiometabolic traits during adolescence; (2) to evaluate the association of metal exposures with changes in DNA methylation and DNA methylation age during adolescence; (3) to evaluate the association of metal exposures with changes in leukocyte telomere length during adolescence. The proposed epidemiologic research during adolescence will provide new data to unravel the effects of metal exposures on cardiovascular diseases' pathogenesis in very early stages. This research may offer novel findings for DNA methylation and telomere length as biosensors of metal exposures, leveraged in future studies to identify individuals at high risk of cardiometabolic dysfunction and other relevant adverse health outcomes.