Effects of an extreme natural disaster on immunity and aging

极端自然灾害对免疫力和衰老的影响

基本信息

批准号：
10385536
负责人：
Marina Watowich
金额：
$ 4.28万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-01 至 2022-12-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10385536
关键词：
Address Adolescent Adult Adverse event Affect Age Aging American Animal Model Behavioral Biological Biological Aging Biology Blood specimen Cardiovascular Diseases Cells Characteristics Chronology DNA DNA Methylation Data Data Collection Demographic Factors Disasters Disease Event Exhibits Female Frequencies Funding Gene Expression Gene Expression Regulation Genetic Genetic Transcription Goals Health Heterogeneity Hospitalization Human Hurricane Immune Immune System Diseases Immune response Immune system Immunity Immunologics Incidence Individual Investigation Island Knowledge Lead Link Macaca Macaca mulatta Measures Mental Health Modeling Modification Molecular Natural Disasters Natural experiment Older Population Outcome Pattern Peripheral Phenotype Population Predisposition Publications Puerto Rico RNA Recovery Regulator Genes Research Risk Sampling Severities Shapes Social Behavior Social status Socioeconomic Status Source Testing Transcriptional Regulation Vulnerable Populations Weather Whole Blood Work age effect arm climate change experience genomic data immune function insight male negative affect nonhuman primate peripheral blood premature relating to nervous system response severe weather sex social social adversity social factors social integration sociodemographics systemic inflammatory response therapy development training opportunity transcriptomics translational model weather-related disaster

项目摘要

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.

项目概要极端不利的环境事件，例如大飓风，与发病率增加和有趣的是，其中许多疾病在老年人中也更为普遍。这表明逆境和衰老以类似的方式共同影响免疫系统。不良经历可能会加速免疫系统老化，破坏免疫基因调节。持续多年，预计将成为极端自然现象的一种特别显着的机制。此外，灾害还会导致与衰老相关的健康状况下降。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），实际年龄和性别与灾难后不同的健康结果有关。迄今为止的研究主要集中在没有基线数据的情况下机会性收集的样本，并且没有一项研究研究极端飓风是否会加速基因表达和 DNA 甲基化以及如何加速社会经历、实际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优势来解决这些差距最近经历过的来自圣地亚哥岛的恒河猴（Macaca mulatta）样本飓风玛丽亚是转化人类衰老研究的成熟动物模型，因为它们与人类有许多共同的遗传、社会和免疫学特征。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，用于飓风玛丽亚之前三年（2014-2016 年）和一年之后（2018 年）的 DNA 血液样本。收集自 2010-2016 年和 2018 年。我将利用这个独特的机会来调查飓风玛丽亚及其后果对外周免疫系统基因调控和生物衰老的影响量化外周基因表达和 DNA 甲基化的变化和老化，这一目标将得到扩展。研究极端自然灾害的逆境和免疫基因调控并量化免疫系统老化其次，我将衡量社会逆境、实际年龄和性别对外围因素的影响。基因表达、DNA 甲基化和衰老速度这一目标将深入了解这些因素如何发挥作用。影响免疫反应的异质性并调节大飓风后的免疫衰老。这些研究将共同深入了解极端自然灾害如何影响免疫基因监管以及一些相关的社会和人口因素如何影响这些反应。工作将增加关于自然灾害和免疫基因调控破坏的不断增长的研究，引入社会人口统计数据的整合来评估免疫多个领域的异质性这项工作为该研究员提供了一个令人难以置信的培训机会，并将提供有关老龄化的宝贵见解。极端灾害如何导致不良健康结果以及谁最容易受到这些负面影响。