The Microbiome and Biological Aging in the Add Health Study

摘要 与年龄相关的免疫失调和炎症增加，称为炎症，已经被 一直与最常见的年龄相关疾病有关，但个体间的确切病因 发炎的不同之处尚不清楚。免疫力和炎症的变化贯穿一生。 当然，但在非老年人口中对这些过程的研究一直有限。这事很重要 因为在人到老年之前确定生物衰老和炎症的来源可能会有所帮助 确定干预点。肠道微生物区系的组成已经在动物模型中显示出来 对免疫系统有深远的影响，并与之相互作用。来自无菌小鼠的发现 表明肠道共生微生物是炎症的关键原因，但这一假说一直不太好- 在人类身上进行了探索。目前很少有数据研究微生物组如何与 衰老生物学的基本方面，特别是炎症表型和生物学的基因组标志物 年龄。我们建议通过收集和分析，填补目前关于衰老的微生物组研究的空白 全国青少年至成人健康纵向研究(Add Health)中的口腔和肠道微生物组数据 具有全国代表性的成年人纵向队列，具有广泛的社会环境数据和现有的或 目前正在对炎症和衰老的基因组和表型标志物进行分析。具体目标包括 1)收集舌和大便标本，用来描述口腔和肠道微生物群的特征 全国代表性样本(N~10,155)ADD健康参与者(平均年龄~40岁)；2)测试 衰老和炎症的微生物组和生物标记物之间的关系，以及一种新的 “微生物群年龄钟”；3)生命过程暴露与微生物群关系的检验 与成年后衰老和炎症的生物标记物有关的物种；4)记录和传播 从该项目生成的数据。这项建议代表了第一项评估口腔和肠道 微生物组与DNA甲基化、衰老和炎症的生物标记物有关 具有代表性的中年成年人样本。我们的学习将极大地促进我们对生活的理解 孕期到成年期的过程暴露形成炎症和DNA的微生物组标志 甲基化老化。这是至关重要的，因为识别成年生物衰老的微生物组标志将 使我们能够通过微生物组更好地识别早期衰老的迹象。

ABSTRACT Age-related immune dysregulation and increases in inflammation, termed inflammaging, have been consistently implicated in most common age-related diseases, but the precise etiology of inter-individual differences in inflammaging are unknown. Changes in immunity and inflammation occur throughout the life course, but research on these processes among non-elderly populations has been limited. This is important because identifying sources of biological aging and inflammation before individuals reach older age may help identify points for intervention. The composition of the gut microbiota has been shown in animal models to have profound influence over, and interactions with, the immune system. Findings from germ-free mice suggest that commensal gut microbes are a key cause of inflammaging, but this hypothesis has not been well- explored in humans. There are currently very few data examining how the microbiome relates to the fundamental aspects of aging biology, specifically inflammatory phenotypes and genomic markers of biological age. We propose to fill gaps in current microbiome research on aging, through the collection and analysis of oral and gut microbiome data in The National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative longitudinal cohort of adults with extensive social environment data and existing or ongoing analyses of genomic and phenotypic markers of inflammation and aging. The specific aims include the: 1) Collection of tongue and stool specimens with which to characterize the oral and gut microbiome in a nationally-representative sample (N ~10,155) of Add Health participants (mean age ~40); 2) Testing the association between the microbiome and biomarkers of aging and inflammation, and the creation of a novel “microbiome age clock”; 3) Examination of the relationships between life course exposures and microbiome species related to biomarkers of aging and inflammation as an adult; 4) Documentation and dissemination of data generated from this project. This proposal represents the first study to assess how the oral and gut microbiome are associated with biomarkers of DNA methylation aging and inflammation in a large US representative sample of midlife adults. Our study will significantly advance our understanding of the life course exposures from gestation to adulthood that shape microbiome markers of inflammaging and DNA methylation aging. This is crucial because identifying microbiome markers of biological aging in adulthood will allow us to better identify signs of early aging via the microbiome.