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、恒河猴和韦氏猕猴 与人类一样容易受到与年龄相关的健康挑战和疾病的影响。年的总体老龄化轨迹 NHP也会受到与人类相似的压力源和生活方式的影响。NHP的研究允许受控 与人类研究相比，提供的纵向数据具有更少的“噪音”。遗传、新陈代谢和 NHP与人类之间的生理相似性使得NHP中的发现可以直接翻译到我们的 对人类疾病过程的理解，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 这些物种可以被用来更好地理解人类衰老的分子和细胞机制， 2)实现了Monkey Inventory and Data Management of Samples(MIDAS)，一个LabKey服务器数据 管理系统，用于将基因组数据和系谱数据与目标1的临床和研究数据集成。 在随后的R33阶段，我们将展示这种协调的、比较的交叉的独特价值 使用综合组学和临床措施量化肝脏和肾脏衰老研究的物种资源 在这四个NHP中，血浆的寿命。我们将1)确定每个NHP的生物学年龄轨迹 来自多个年代的物种，通过测量分子捕捉到相当于人类18-80年的年龄 已知的反映生物年龄的因素，包括肝脏样本中的基因表达、DNA甲基化和蛋白质(n=48 对于每个物种(F，24；M，24)；以及2)识别与肝脏特异性相关的循环分子特征 四个NHP物种排列的常见临床衰老标记之前的衰老特征和 协调这四个国家惠普群体的数据和样本将提供关键的资源翻译 对人类的发现，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.