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

• 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
• 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

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.

项目摘要 极端不利的环境事件，例如重大飓风，与事件的增加有关 无数健康问题的严重程度。有趣的是，这些疾病中的许多疾病在较旧的情况下也更为普遍 个人 - 冒险和衰老以类似的方式影响免疫系统。在一起，这表明 广告体验可能会加速免疫系统的衰老。对免疫调节的干扰可以 持续多年，预计将是一种特别自然的机制 灾难推动与衰老相关的健康下降。此外，个人在其自己的 对广告的回应以及社交广告（即社会经济地位，社会融合）等因素， 年龄和性别与灾难后的差异健康结果有关。但是，大多数 迄今为止的研究集中于没有基线数据的机会主义收集的样本，没有一个 研究了基因表达和DNA甲基化是否通过极端飓风加速 社会经验，年龄和性别会影响免疫基因调节和衰老的多个领域。 拟议研究的目的是通过利用无与伦比的利用来解决这些差距 来自Cayo Santiago岛的Rhesus Macaques（Macaca Mulatta）样本 玛丽亚飓风。猕猴是转化人类衰老研究的良好动物模型，因为 他们与人类共享许多遗传，社会和免疫学特征。外围全血样本 每年从少年和成年男性和女性猕猴的代表性样本中收集RNA 在（2014-2016）和（2018）飓风玛丽亚（Maria）之后的一年之前，紧接三年。 DNA的血液样本 从2010- 2016年和2018年收集。我将利用这个独特的机会调查 玛丽亚飓风及其对外周免疫系统基因调节和生物老化的后果 量化周围基因表达和DNA甲基化的变化和衰老。这个目标将扩展 对极端自然灾害的广告和免疫法规的研究并量化免疫系统老化 在多个级别。其次，我将衡量社交广告，年代年龄和性别对周围的影响 基因表达和DNA甲基化以及衰老的空间。这个目标将提供有关这些因素如何 影响免疫反应的异质性，并在重大飓风后调节免疫老化。 这些研究将共同​​了解极端自然灾害如何影响免疫基因 调节以及几个相关的社会和人口因素如何塑造这些反应。提议 工作将增加关于自然灾害和免疫基因调节性中断和 引入社会人口统计数据的整合以评估免疫多个领域的异质性 老化。这项工作为同伴代表了令人难以置信的培训机会，并将为您提供宝贵的见解 极端灾难如何推动健康状况不佳，谁最容易受到这些负面影响。