Development of a Wake Forest Multi-Species NHP Biorepository to Support Interdisciplinary Aging Studies

ASTRACT 非人灵长类动物（NHP），如狒狒、食蟹猴、恒河猴和长尾猴， 易受与人类相同的年龄相关的健康挑战和疾病的影响。整体的老化轨迹 NHP也受到压力和生活方式的影响，与人类相似。NHP的研究允许控制 环境中，提供纵向数据与较少的“噪音”比人类的研究。基因、代谢和 NHP和人类之间的生理相似性使得NHP的发现可以直接转化为我们的研究结果。 了解人类疾病过程，包括遗传易感性和早期分子指标， 这些过程。在该项目的R21阶段，我们将1）协调四个NHP中的现有样本和数据 这些物种可以用来更好地了解人类衰老的分子和细胞机制， 和2）实施猴库存和样品数据管理（MIDAS），一个LabKey服务器数据 管理系统，用于将组学数据和谱系数据与目标1的临床和研究数据整合。 在随后的R33阶段，我们将展示这种协调的、比较性的交叉研究的独特价值。 使用综合组学和临床措施量化肝脏衰老的衰老研究的物种资源， 在这四个NHP的寿命期间的血浆。我们将1）确定每个NHP的生物年龄轨迹 从多个年代年龄的物种，捕捉相当于人类18-80岁，通过测量分子 已知反映生物学年龄，包括基因表达、DNA甲基化和肝脏样品中的蛋白质（n=48 对于每个物种（F，24; M，24））;和2）鉴定与肝脏特异性免疫应答相关的循环分子特征。 在四种NHP物种比对中常见的衰老临床标志物之前的衰老特征， 协调这四个国家卫生计划群组的数据和样本将提供关键资源， 这些发现对人类的影响，并支持跨学科的跨寿命衰老研究。

ASTRACT Non-human primates (NHP) such as baboon, cynomolgus macaque, rhesus macaque, and vervet are susceptible to the same age-related health challenges and diseases as humans. The overall aging trajectory in NHP is also influenced by stressors and lifestyle similar to humans. Research in NHP allows for controlled environments, providing longitudinal data with less “noise” than in human studies. The genetic, metabolic and physiologic similarities between NHP and humans make findings in NHP directly translatable to our understanding of human disease processes, including genetic predispositions and early molecular indicators of these processes. In the R21 phase of this project, we will 1) harmonize existing samples and data in four NHP species that can be leveraged to better understand molecular and cellular mechanisms underlying human aging, and 2) implement the Monkey Inventory and Data management of Samples (MIDAS), a LabKey Server data management system, for integration of omic data and pedigree data with clinical and research data from Aim 1. In the subsequent R33 phase, we will demonstrate the unique value of this harmonized, comparative cross- species resource for aging studies using integrated omics and clinical measures to quantify aging in liver and plasma across the lifespan in these four NHP. We will 1) determine the biological age trajectory for each NHP species from multiple chronological ages that capture human equivalent 18-80 years, by measuring molecules known to reflect biological age including gene expression, DNA methylation, and proteins in liver samples (n=48 for each species (F, 24; M,24)); and 2) identify circulating molecular signatures that correlate with liver specific signatures of aging that precede clinical markers of aging common to the four NHP species Alignment and harmonization of data and samples for these four NHP cohorts will provide a critical resource translating discoveries to humans, and supporting interdisciplinary studies of aging across the lifespan.