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: 10468876
• 负责人: Laura A Cox
• 金额: $ 17.82万
• 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 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10468876
• 关键词: Adult; Age; Aging; Alzheimer' s Disease; Animals; Biological; Biological Clocks; Blood; Blood specimen; Cardiovascular Diseases; Cardiovascular Models; Chronology; Clinical; Clinical Markers; Clinical Research; Computer software; Controlled Environment; DNA Methylation; Data; Data Management Resources; Data Storage and Retrieval; Databases; Dementia; Development; Diabetes Mellitus; Diet; Dietary Intervention; Disease; Equipment and supply inventories; Female; Funding; Future; Gene Expression; Genetic; Genetic Predisposition to Disease; Genotype; Goals; Health; Hormones; Human; Interdisciplinary Study; Intervention; Lead; Life Cycle Stages; Life Style; Liver; Longevity; Macaca fascicularis; Macaca mulatta; Measures; Metabolic; Metabolic Diseases; Modeling; Molecular; Molecular Profiling; Monkeys; Noise; Obesity; Paper; Papio; Pathway interactions; Phase; Phenotype; Physiological; Plasma; Primates; Process; Proteins; RNA; Radiation exposure; Records; Research; Research Personnel; Resources; Rhesus; Sampling; Stress; Systems Integration; Tissues; Translating; United States National Institutes of Health; Work; age related; base; biobank; clinical development; clinically relevant; cohort; comparative; data harmonization; data management; data sharing; database query; forest; genetic pedigree; human disease; immune function; male; nonhuman primate; normal aging; open source; phenotypic data; protein metabolite; sample archive; stressor; vervet

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.

ASTRACT 非人类灵长类动物（NHP），例如狒狒，cynomolgus猕猴，恒河猕猴和Vervet 容易受到与人类相同的与年龄相关的健康挑战和疾病的影响。整体衰老轨迹 NHP还受到与人类类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，环境提供的纵向数据“噪声”少。遗传，代谢和 NHP和人类之间的生理相似性在NHP中可以直接翻译成我们 了解人类疾病过程，包括遗传倾向和早期分子指标 这些过程。在该项目的R21阶段，我们将1）在四个NHP中协调现有样本和数据 可以利用人类衰老的分子和细胞机制的物种， 2）实施猴子库存和样本的数据管理（MIDAS），Labkey Server数据 管理系统，用于将OMIC数据和谱系数据与AIM 1的临床和研究数据集成。 在随后的R33阶段中，我们将证明这种统一的，比较跨的独特值 使用综合的OMIC和临床措施进行衰老研究的物种资源，以量化肝脏的衰老和 这四个NHP的寿命中的等离子体。我们将1）确定每个NHP的生物年龄轨迹 通过测量分子来捕获人类当量18-80岁的多个年代年龄的物种 已知可以反映生物年龄，包括基因表达，DNA甲基化和肝样品中的蛋白质（n = 48 对于每个物种（F，24; m，24））; 2）确定与肝脏特异性相关的循环分子特征 在四个NHP物种一致性和 这四个NHP队列的数据和样本的协调将提供关键的资源翻译 对人类的发现，并支持整个生命周期衰老的跨学科研究。