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的研究允许受控环境，提供比人类研究更少“噪音”的纵向数据。NHP与人类在遗传、代谢和生理上的相似性使得NHP的发现可以直接转化为我们对人类疾病过程的理解，包括遗传易感性和这些过程的早期分子指标。在该项目的R21阶段，我们将1)协调四种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，2)实施猴类样本库存和数据管理（MIDAS），这是一个LabKey Server数据管理系统，用于将组学数据和谱系数据与Aim 1的临床和研究数据整合起来。在随后的R33阶段，我们将展示这种统一的、比较的跨物种资源在衰老研究中的独特价值，使用综合组学和临床测量来量化这四种NHP的肝脏和血浆在整个生命周期中的衰老。我们将1)通过测量反映生物年龄的已知分子，包括基因表达、DNA甲基化和肝脏样本中的蛋白质，从多个实足年龄（相当于人类18-80岁）中确定每个NHP物种的生物年龄轨迹（n=48，每个物种（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，这些特征先于四种NHP物种共同的衰老临床标志物，这四种NHP队列的数据和样本的校准和协调将为将发现转化为人类提供关键资源，并支持跨生命周期的衰老跨学科研究。