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

开发维克森林多物种 NHP 生物样本库以支持跨学科衰老研究

• 批准号: 10909446
• 负责人: Laura A Cox
• 金额: $ 77.5万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10909446
• 关键词: Development; Wake; Forest; Multi; Species

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.

非人类灵长类动物（NHP），如狒狒、食蟹猴、恒河猴和黑长尾猴，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，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下提供比人类研究“噪音”更少的纵向数据 NHP 和人类之间的遗传、代谢和生理相似性使得 NHP 的发现可以直接转化为我们的理解。人类疾病过程的研究，包括这些过程的遗传倾向和早期分子指标。在该项目的 R21 阶段，我们将 1) 协调四个 NHP 物种的现有样本和数据，以更好地了解人类潜在的分子和细胞机制。老化，以及 2) 实施猴子库存和样本数据管理 (MIDAS)，这是一个 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 的临床和研究数据集成。在随后的 R33 阶段，我们将展示这种统一的跨物种比较资源对于衰老研究的独特价值，使用综合组学和临床措施来量化这四种 NHP 整个生命周期中肝脏和血浆的衰老情况，我们将 1) 确定通过测量已知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 n = 48 (F, 24; M,24)); 2) 识别与肝脏特异性衰老特征相关的循环分子特征，这些特征先于四个 NHP 物种常见的衰老临床标志 这四个 NHP 群体的数据和样本的对齐和协调将提供重要的资源，将发现转化为人类，并支持整个生命周期衰老的跨学科研究。