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CELLULAR AND MOLECULAR GEROSCIENCE CoBRE

细胞和分子老年科学 CoBRE

基本信息

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
项目类别：
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

项目摘要

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任何人体组织中的甲基化都会发生变化。我们建议测试这些时钟的关联认知和血管病理学，以及生成旨在预测年龄的新时钟相关的功能障碍。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 相关联来获取样本甲基化数据。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。目标1 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血液样本中的认知障碍。我们将测试 Horvath、Levine、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来自人体样本的血管健康状况。我们将从之前收集的甲基化数据中生成白细胞，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）。我们假设这个年龄加速度应与中枢认知和血管功能呈负相关循环和外围。这些分析将为确定是否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公共数据荟萃分析中与 AD 和认知障碍的关联。使用相同的目标 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损害而不是实际年龄。我们假设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

期刊论文数量（28）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

DOI：
10.3389/fnagi.2022.876816
发表时间：
2022
期刊：
Frontiers in aging neuroscience
影响因子：
4.8
作者：
通讯作者：

Time-restricted feeding (TRF) for prevention of age-related vascular cognitive impairment and dementia.

时间限制的喂养（TRF）用于预防与年龄有关的血管认知障碍和痴呆。

DOI：
10.1016/j.arr.2020.101189
发表时间：
2020-12
期刊：
Ageing research reviews
影响因子：
13.1
作者：
Balasubramanian P;DelFavero J;Ungvari A;Papp M;Tarantini A;Price N;de Cabo R;Tarantini S
通讯作者：
Tarantini S

Improving Cognitive Function with Nutritional Supplements in Aging: A Comprehensive Narrative Review of Clinical Studies Investigating the Effects of Vitamins, Minerals, Antioxidants, and Other Dietary Supplements.

DOI：
10.3390/nu15245116
发表时间：
2023-12-15
期刊：
Nutrients
影响因子：
5.9
作者：
Fekete M;Lehoczki A;Tarantini S;Fazekas-Pongor V;Csípő T;Csizmadia Z;Varga JT
通讯作者：
Varga JT

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