The Microbiome and Biological Aging in the Add Health Study

摘要 免疫相关的免疫失调和炎症增加，称为炎症，已经被发现。 一直牵连在大多数常见的年龄相关疾病，但确切的病因，个体间 炎症的差异是未知的。免疫和炎症的变化发生在整个生命过程中 当然，但在非老年人群中对这些过程的研究有限。这很重要 因为在个体达到老年之前识别生物老化和炎症的来源可能有助于 确定干预要点。在动物模型中已经显示肠道微生物群的组成， 对免疫系统有着深远的影响和相互作用。无菌小鼠的发现 这表明肠道微生物是炎症的关键原因，但这一假设并没有得到很好的证实- 在人类身上探索。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记物， 年龄我们建议通过收集和分析 口腔和肠道微生物组数据在国家青少年到成人健康纵向研究（添加健康）， 具有广泛社会环境数据的全国代表性成人纵向队列， 正在进行的炎症和衰老的基因组和表型标志物的分析。具体目标包括 1）收集舌和粪便标本，用于表征口腔和肠道微生物组， AddHealth参与者（平均年龄约40岁）的全国代表性样本（N约10，155）; 2）测试 微生物组与衰老和炎症的生物标志物之间的关联，以及一种新的 “微生物组年龄时钟”; 3）检查生命过程暴露与微生物组之间的关系 与衰老和炎症的生物标志物相关的物种; 4）记录和传播 这个项目产生的数据。这项提案代表了第一项评估口腔和肠道如何 微生物组与DNA甲基化、衰老和炎症的生物标志物相关， 中年人的典型样本。我们的研究将大大促进我们对生命的理解 从妊娠期到成年期的过程暴露，形成炎症和DNA的微生物组标志物 甲基化老化这一点至关重要，因为确定成年期生物衰老的微生物组标志物将有助于 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.