Effects of an extreme natural disaster on immunity and aging

项目总结 极端不利的环境事件，如大飓风，与发病率增加和 一系列健康问题的严重性。有趣的是，其中许多疾病在老年人中也更为普遍。 个体--暗示逆境和衰老以相似的方式影响免疫系统。总而言之，这表明 这种不良经历可能会加速免疫系统的老化。免疫基因调控的中断可能 持续多年，预计将是极端自然 灾难会导致与衰老相关的健康状况下降。此外，个体在他们的 对逆境的反应，以及社会逆境等因素(即社会经济地位、社会融合)， 在灾难发生后，年龄和性别与不同的健康结果有关。然而，大多数 到目前为止，研究的重点是在没有基线数据的情况下机会性地收集样本，而且还没有一个 调查了极端飓风是否会加速基因表达和DNA甲基化，以及如何 社会经历、年龄和性别影响免疫基因调节和衰老的多个领域。 拟议研究的目标是通过利用无与伦比的 最近在圣地亚哥岛经历的恒河猴(Macaca Mulatta)样本 飓风玛丽亚。猕猴是翻译人类衰老研究中公认的动物模型，因为 它们与人类有许多共同的遗传、社会和免疫学特征。外周全血样本 每年从幼年和成年雄性和雌性猕猴的代表性样本中收集RNA，用于 紧接在(2014-2016)飓风玛丽亚之前的三年和(2018)飓风玛丽亚之后的一年。血液样本中的DNA 是在2010-2016年和2018年收集的。我将利用这个独特的机会来调查 飓风玛丽亚及其对外周免疫系统基因调控和生物老化的影响 量化外周基因表达和DNA甲基化的变化和老化。这一目标将延伸到 极端自然灾害的逆境与免疫基因调控及免疫系统老化量化研究 在多个层面上。其次，我将测量社会逆境、年龄和性别对外围设备的影响 基因表达、DNA甲基化和衰老速度。这一目标将提供对这些因素如何 影响免疫反应的异质性，并调节主要飓风后的免疫老化。 总之，这些研究将深入了解极端自然灾害是如何影响免疫基因的。 监管以及几个相关的社会和人口因素如何塑造这些反应。建议数 这项工作将增加越来越多关于自然灾害和免疫基因调控中断的研究，以及 引入社会人口数据的整合，以评估免疫多个领域的异质性 衰老。这项工作对这位研究员来说是一个难以置信的培训机会，并将为 极端灾难如何导致糟糕的健康结果，以及谁最容易受到这些负面影响的影响。

PROJECT SUMMARY Extreme adverse environmental events, such as major hurricanes, are associated with increased incidence and severity of a myriad of health problems. Intriguingly, many of these ailments are also more prevalent in older individuals–hinting that adversity and aging affect the immune system in similar ways. Together, this suggests that adverse experiences may accelerate immune system aging. Disruptions to immune gene regulation can persist for many years and are expected to be a particularly salient mechanism by which extreme natural disasters drive aging-associated health declines. Additionally, individuals exhibit extensive heterogeneity in their responses to adversity, and factors such as social adversity (i.e., socioeconomic status, social integration), chronological age, and sex have been linked to differential health outcomes following disaster. However, most studies to date have focused on opportunistically collected samples without baseline data, and none have investigated whether gene expression and DNA methylation are accelerated by extreme hurricanes and how social experiences, chronological age, and sex affect multiple domains of immune gene regulation and aging. The goal of the proposed research is to address these gaps by taking advantage of an unparalleled sample of rhesus macaques (Macaca mulatta) from the island of Cayo Santiago that recently experienced Hurricane Maria. Macaques are a well-established animal model for translational human aging research because they share many genetic, social, and immunological features with humans. Peripheral whole blood samples for RNA were collected annually from representative samples of juvenile and adult male and female macaques for three years immediately prior to (2014-2016) and one year after (2018) Hurricane Maria. Blood samples for DNA were collected from 2010-2016 and in 2018. I will use this unique opportunity to investigate the effects of Hurricane Maria and its aftermath on gene regulation and biological aging of the peripheral immune system by quantifying changes to and aging of peripheral gene expression and DNA methylation. This aim will extend studies of adversity and immune gene regulation to extreme natural disaster and quantify immune system aging at multiple levels. Second, I will measure the effects of social adversity, chronological age, and sex on peripheral gene expression and DNA methylation and pace of aging. This aim will provide insight into how these factors influence the heterogeneity in immune responses and modulate immune aging following a major hurricane. Together, these studies will provide insight into how extreme natural disasters impact immune gene regulation and how several pertinent social and demographic factors shape these responses. The proposed work will add to the growing body of research on natural disaster and immune gene regulatory disruptions and introduce the integration of socio-demographic data to evaluate heterogeneity in multiple domains of immune aging. This work represents an incredible training opportunity for the fellow and will provide valuable insight into how extreme disasters drive poor health outcomes and who is most vulnerable to these negative effects.