Specific Pathogen Free Baboon Research Resource (SPFBRR) - Administrative Supplement (Epigenetic)

项目摘要/摘要 表观遗传年龄是一种新的、强大的衰老生物标志物，其表现优于其他分子和表型 衰老的生物标志物在预测发病率和死亡率中的作用。表观遗传年龄是用DNA甲基化计算的 在基因组的特定位置的水平，以创建DNA甲基化时钟(DMC)。然后使用DMC来查找 一个人的表观遗传年龄和实际年龄之间的偏差，这决定了 个人表现出年龄加速，这与一系列与年龄有关的疾病有关，包括 AD/ADRD。然而，DMCs还没有被开发出来用于狒狒，这是一种常用的各种动物模型 与衰老相关的疾病。鉴于狒狒表现出AD神经病的特征，有必要进一步 作为衰老和阿尔茨海默病模型的研究进展。德克萨斯大学医学博士安德森癌症 该中心(MDACC)正在生长和维护世界上唯一的无病毒的不定区域狒狒繁殖地 (无特定病原体的浣熊研究资源)。因此，拟议的行政补充 P40的父母拨款要求额外的资金，以检查作为加速的动物模型的狒狒 衰老，并建立AD和衰老相关生物标记物的基线数据，以增加这一用途 研究资源。在目标1中，我们建议使用DNA甲基化水平在 175只3-19岁的母养和苗圃饲养的狒狒。我们将使用该DMC按时间顺序进行预测 年龄，以及时间和表观遗传年龄之间的差异将被用来识别 显示年龄加速。此外，鉴于育儿(一种早期生活压力)与宿主有关 对行为和生理的有害影响，我们将调查养育方式与 并加速衰老。如果这真的加速了衰老，苗圃饲养的狒狒将是一个重要的 早期生活应激、衰老与阿尔茨海默病发展的实验动物模型。在目标2中，我们将确立 AD/ADRD生物标志物的基线水平，以及确定在该狒狒模型中年龄加速 与所述生物标记物相关联。多路Luminex生物标志物将包括18-plex的血浆水平 神经科学小组包括AD/ADRD生物标志物，如淀粉样蛋白和tau蛋白，糖尿病的10个复合体 生物标志物、中性粒细胞与淋巴细胞比率(NLR)以及行为标志物(即行走速度和运动 表现)，在来自目标1的175只狒狒中的两个时间点。我们还将检查这些水平 在两个时间点(15年和15年)，20只老年狒狒的脑脊液中的生物标记物 提议的项目将在P40家长拨款下创建更明确的研究资源1) 创建加速衰老的实验模型，可用于测试受控的干预措施 设置；以及2)在狒狒样本中建立AD/ADRD生物标记物的基线，从而增加 人口特征和纵向AD/ADRD研究的开放途径。

Project Summary/Abstract Epigenetic age is a new, robust biomarker of aging that has outperformed other molecular and phenotypic biomarkers of aging in predicting morbidity and mortality. Epigenetic age is calculated using DNA methylation levels at specific sites in the genome to create a DNA methylation clock (DMC). The DMC is then used to find the deviation between an individual’s epigenetic age and chronological age, which determines whether the individual shows age-acceleration, which has been implicated in a host of age-related diseases, including AD/ADRD. However, DMCs have not been developed for baboons, a commonly-used animal model for various aging-related diseases. Given that baboons show hallmarks of AD neuropathy, there is a need for further development of the baboon as a model for aging and AD. The University of Texas MD Anderson Cancer Center (MDACC) is growing and maintaining the world’s only adventitious virus-free baboon breeding colony (Specific Pathogen Free Baboon Research Resource). Therefore, the proposed administrative supplement to the P40 parent grant is requesting additional funds to examine baboons as an animal model for accelerated aging, and to establish baseline data for AD and aging-associated biomarkers to increase the utility of this research resource. In Aim 1, we propose using DNA methylation levels to create a baboon-specific DMC in 175 mother- and nursery-reared baboons aged 3-19 years old. We will use this DMC to predict chronological age, and the discrepancy between chronological and epigenetic age will be used to identify individuals that show age acceleration. Additionally, given that nursery-rearing (an early life stressor) is associated with a host of deleterious effects on behavior and physiology, we will investigate the relationship between nursery-rearing and accelerated aging. If this indeed accelerates aging, nursery-reared baboons would serve as an important experimental animal model of early life stress, aging, and the development of AD. In Aim 2, we will establish baseline levels of AD/ADRD biomarkers, as well as determine whether age acceleration in this baboon model is associated with said biomarkers. Multiplexed Luminex biomarkers will include plasma levels of an 18-plex neuroscience panel including AD/ADRD biomarkers such as amyloid and tau proteins, a 10-plex of diabetes biomarkers, neutrophil to lymphocyte ratio (NLR), as well as behavioral markers (i.e., walking speed and motor performance), at two time points in the 175 baboons from Aim 1. We will also examine levels of these biomarkers in cerebrospinal fluid in a subset of 20 geriatric baboons at two time points as well (15 years and older).The proposed project will create a better-defined research resource under the P40 parent grant by 1) creating an experimental model of accelerated aging that can be used to test interventions in controlled settings; and 2) establish baselines of AD/ADRD biomarkers in the baboon sample, thereby increasing characterization of the population and opening avenues for longitudinal AD/ADRD research.