Impact of Metals on Biological Aging and Cardiometabolic Traits in Adolescents

摘要 环境中普遍存在的有毒金属暴露是全球公共卫生问题， 处境不利的人口不成比例地受到和容易受到不利影响。铅砷 镉和汞是最常见的有毒环境金属暴露 人口这些金属暴露出现在有毒物质和疾病机构的前7名中 注册物质优先级列表，根据物质的频率、毒性和 人体暴露的可能性。人口研究的观察结果支持这些金属之间的关联 暴露和心血管疾病在成年期;然而，文献是稀疏的早期生活 心脏代谢健康的影响。对儿童心血管疾病起源的研究表明， 生活因素影响整个生命过程中的心血管风险，青春期是一个敏感的发展阶段， 环境 引起生物老化的因素，如支持性改变， 这些作为了解早期生活金属暴露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， 填补现有科学文献中的空白将改善接触补救和风险降低 在最脆弱的人群中实施战略，并为新的疾病预防机会提供支持。 拟议的流行病学研究将提供以下方面的见解：（1）金属对生命早期健康的影响 暴露，（2）金属共暴露的影响，（3）青春期作为心脏代谢的敏感期， 表型编程，以及（4）金属暴露引起心脏代谢的作用机制 功能障碍本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 轨迹和青春期的生物老化。我们将利用已建立的孟加拉国 儿童健康环境研究（BiRCH）队列，由居住在农村的500名青年组成 孟加拉国.入组的受试者在拟定的首次研究访视时年龄为11至13岁。 我们提出以下具体目标：（1）评估金属暴露与纵向 青春期的心脏代谢特征;（2）评估金属暴露与 DNA甲基化和DNA甲基化年龄在青春期;（3）评估金属相关性 白细胞端粒长度的变化。建议的流行病学 青少年时期的研究将提供新的数据来揭示金属暴露对心血管疾病的影响。 疾病的发病机制在非常早期的阶段。这项研究可能会为DNA甲基化提供新的发现， 端粒长度作为金属暴露的生物传感器，在未来的研究中利用，以识别高风险个体 心脏代谢功能障碍和其他相关的不良健康后果。

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.