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

非人灵长类动物(NHP)，如狒狒、食蟹猴、恒河猴和弗韦特，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。NHP的整体衰老轨迹也受到与人类相似的压力源和生活方式的影响。NHP的研究允许在受控环境中进行，提供的纵向数据比人类研究中的“噪音”更少。NHP与人类之间的遗传、代谢和生理相似之处使NHP的发现可以直接翻译为我们对人类疾病过程的理解，包括这些过程的遗传易感性和早期分子指标。在这个项目的R21阶段，我们将1)协调四个NHP物种的现有样本和数据，以便更好地了解人类衰老的分子和细胞机制，以及2)实施Monkey Inventory and Data Management of Samples(MIDAS)，这是一个LabKey服务器数据管理系统，用于整合基因组数据和系谱数据与AIM 1的临床和研究数据。在随后的R33阶段，我们将使用集成的组学和临床措施来量化这四个NHP中肝脏和血浆中的衰老，展示这种协调的、可比较的跨物种资源在衰老研究中的独特价值。我们将1)通过测量已知的反映生物年龄的分子，包括基因表达、DNA甲基化和肝脏样本中的蛋白质(每个物种48人(女性，24人；男性，24人))，从捕捉人类相当于18-80岁的多个年龄段确定每个NHP物种的生物年龄轨迹；以及2)识别与四个NHP物种共同的临床衰老标记之前的肝脏特定衰老特征相关的循环分子特征，并协调这四个NHP群体的数据和样本，将提供一个关键资源，将发现转化为人类，并支持跨寿命的跨学科衰老研究。

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.