CELLULAR AND MOLECULAR GEROSCIENCE CoBRE

细胞和分子老年科学 CoBRE

• 批准号: 10851465
• 负责人: William Edmund Sonntag
• 金额: $ 41.39万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10851465
• 关键词: Acceleration; Age; Aging; Animal Model; Bioinformatics; Biological Markers; Blood; Blood Vessels; Blood specimen; Brain; Brain Diseases; Centers of Research Excellence; Cephalic; Chronology; Circulation; Clinical; Clinical Trials; Cognition; Cognitive; DNA Methylation; Data; Data Set; Disease; Elderly; Endothelium; Epigenetic Process; Evaluation; Functional disorder; Geroscience; Goals; Health; Human; Impaired cognition; Laser Speckle Imaging; Leukocytes; Literature; Longevity; Manuals; Measures; Mediating; Meta-Analysis; Methylation; Modeling; Molecular; Morbidity - disease rate; Neuropsychological Tests; Paper; Pathology; Patients; Performance; Peripheral; Physiological; Prediction of Response to Therapy; Publishing; Research; Sampling; Science; Testing; Tissues; Training; Treatment Efficacy; Ultrasonography; Validation; Vascular Cognitive Impairment; Vascular Diseases; age related; anti aging; brain tissue; cerebrovascular; cerebrovascular health; clinically relevant; cognitive function; cognitive testing; design; functional disability; functional near infrared spectroscopy; human tissue; laboratory experiment; machine learning model; machine learning prediction; mortality; retina blood vessel structure; young adult

ABSTRACT This project aims to advance aging research by developing a biomarker for aging using a model based upon the epigenetic clock, a machine learning model that predicts age from DNA methylation changes in any human tissue. We propose to test these clocks’ association to cognitive and vascular pathologies, as well as to generate new clocks designed to predict age- related dysfunction. We propose to evaluate the performance of epigenetic clocks in clinical samples by correlating cognitive function and vascular-cognitive impairment measures with DNA methylation data. Our goal is to determine if epigenetic clocks can serve as an aging biomarker using accessible tissue (blood) to predict age-related vascular and cognitive dysfunction. Aim 1 of the project will determine the ability of epigenetic clocks to predict age-associated vascular and cognitive impairment from blood samples. We will test the association between Horvath, Levine, and our own epigenetic clocks’ “age acceleration” and functional data on cognition and brain vascular health from human samples. We will generate methylation data from previously collected white blood cells, which will be paired with cognitive assessment using the Cambridge Neuropsychological Test Automated Battery (CANTAB) of cognitive tests, cerebrovascular health using transcranial doppler (TCD), functional near-infrared spectroscopy (fNIRS), dynamic retinal vessel analysis, and peripheral vascular health using the flow mediated dilation approach in large (ultrasonography) and small vessels (laser speckle contrast imaging). We hypothesize that age acceleration should be negatively correlated with cognitive and vascular function both in central circulation and in the periphery. These analyses will provide evidence critical to determining if epigenetic clocks can be a clinically relevant biomarker for aging in the brain. In the Aim 2, we will design new epigenetic clocks to predict vascular and cognitive impairment and evaluate their association to AD and cognitive impairment in a meta-analysis of public data. Using the same epigenetic data generated in aim 1, we will train new epigenetic clocks that predict functional impairment instead of chronological age. We hypothesize that epigenetic clocks trained to predict vascular and cognitive dysfunction will also be able to predict age-related disease status.

抽象的 该项目旨在通过使用以下方法开发衰老生物标志物来推进衰老研究： 基于表观遗传时钟的模型，这是一种根据 DNA 预测年龄的机器学习模型 我们建议测试这些时钟与任何人体组织的甲基化变化。 认知和血管病理学，以及生成旨在预测年龄的新时钟 我们建议评估表观遗传时钟在临床中的表现。 通过将认知功能和血管认知障碍测量与 DNA 相关联来获取样本 我们的目标是确定表观遗传时钟是否可以作为衰老生物标志物。 使用可及的组织（血液）来预测与年龄相关的血管和认知功能障碍。 该项目的研究将确定表观遗传时钟预测与年龄相关的血管和 我们将测试霍瓦斯、莱文、 以及我们自己的表观遗传时钟的“年龄加速”以及认知和大脑的功能数据 我们将从之前收集的人类样本中生成甲基化数据。 白细胞，将与剑桥认知评估配对 认知测试、脑血管健康的神经心理学测试自动电池（CANTAB） 使用经颅多普勒 (TCD)、功能性近红外光谱 (fNIRS)、动态视网膜 使用流量介导的扩张方法在大范围内进行血管分析和外周血管健康 （超声检查）和小血管（激光散斑对比成像）。 加速度应与中枢认知功能和血管功能呈负相关 这些分析将为确定是否存在提供重要的证据。 表观遗传时钟可以成为大脑衰老的临床相关生物标志物，在目标 2 中，我们将。 设计新的表观遗传时钟来预测血管和认知障碍并评估其 使用相同的公共数据进行荟萃分析，得出 AD 和认知障碍之间的关联。 目标 1 中生成的表观遗传数据，我们将训练新的表观遗传时钟来预测功能 我们发现表观遗传时钟经过训练可以预测。 血管和认知功能障碍也将能够预测与年龄相关的疾病状态。

项目成果

Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation.

MRL/MpJ 小鼠耳部伤口的愈合与肠道微生物组的组成有关，并且可以通过微生物组移植转移到非愈合小鼠身上。

• 发表时间: 2021
• 影响因子: 3.7
• 作者: Velasco, Cassandra;Dunn, Christopher;Sturdy, Cassandra;Izda, Vladislav;Martin, Jake;Rivas, Alexander;McNaughton, Jeffrey;Jeffries, Matlock A
• 通讯作者: Jeffries, Matlock A

Measuring Behavior in the Home Cage: Study Design, Applications, Challenges, and Perspectives.

测量家庭笼子中的行为：研究设计、应用、挑战和前景。

• 发表时间: 2021
• 作者: Grieco, Fabrizio;Bernstein, Briana J;Biemans, Barbara;Bikovski, Lior;Burnett, C Joseph;Cushman, Jesse D;van Dam, Elsbeth A;Fry, Sydney A;Richmond;Homberg, Judith R;Kas, Martien J H;Kessels, Helmut W;Koopmans, Bastijn;Krashes, Mich
• 通讯作者: Krashes, Mich

Progressive cognitive impairment after recovery from neuroinvasive and non-neuroinvasive Listeria monocytogenes infection.

从神经侵袭性和非神经侵袭性单核细胞增生李斯特菌感染恢复后出现进行性认知障碍。

• 发表时间: 2023
• 作者: Cassidy, Benjamin R;Logan, Sreemathi;Farley, Julie A;Owen, Daniel B;Sonntag, William E;Drevets, Douglas A
• 通讯作者: Drevets, Douglas A

Exploring the Influence of Gut-Brain Axis Modulation on Cognitive Health: A Comprehensive Review of Prebiotics, Probiotics, and Symbiotics.

探索肠脑轴调节对认知健康的影响：益生元、益生菌和共生素的综合综述。

• 发表时间: 2024-03-10
• 影响因子: 5.9
• 作者: Fekete, Mónika;Lehoczki, Andrea;Major, Dávid;Fazekas;Csípő, Tamás;Tarantini, Stefano;Csizmadia, Zoltán;Varga, János Tamás
• 通讯作者: Varga, János Tamás

A history of ethanol drinking increases locomotor stimulation and blunts enhancement of dendritic dopamine transmission by methamphetamine.

饮酒史会增加运动刺激并减弱甲基苯丙胺对树突状多巴胺传递的增强。

• 发表时间: 2020
• 影响因子: 3.4
• 作者: Tschumi, Christopher W;Daszkowski, Anna W;Sharpe, Amanda L;Trzeciak, Marta;Beckstead, Michael J
• 通讯作者: Beckstead, Michael J