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），例如狒狒，cynomolgus猕猴，恒河猴和vervet，易受与人类相同的与年龄相关的健康挑战和疾病的影响。 NHP中的整体衰老轨迹也受压力源和与人类类似的生活方式的影响。 NHP的研究允许受控环境，提供的纵向数据与人类研究相比，“噪声”少。 NHP和人类之间的遗传，代谢和生理相似性使NHP中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。 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在这四个NHP中，使用综合的OMIC和临床措施来量化肝脏和血浆中衰老的综合跨物种资源的价值。我们将1）通过测量已知反映生物年龄的分子（包括基因表达，DNA甲基化和肝样品中的蛋白质）已知的分子来确定每个NHP物种的生物年龄轨迹，这些年代的生物年龄轨迹从多个年代年代捕获了人类当量18 - 80年（n = 48种）（n = 48种（F，24; 24; m，24）; m，m，24）; 2）确定与肝脏特异性特异性衰老相关的循环分子特征，该标志是在这四个NHP群体中四个NHP物种对齐和数据和样本的衰老临床标志之前，将为人类提供至关重要的资源，并支持人类的跨学科研究。