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Study DNA methylation changes in brain aging and rapamycin treatment

研究大脑衰老和雷帕霉素治疗中 DNA 甲基化的变化

基本信息

批准号：
8766250
负责人：
Xiangru Xu
金额：
$ 24.9万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-30 至 2015-12-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8766250
关键词：
Aberrant DNA Methylation Age Age-associated memory impairment Aged, 80 and over Aging Alzheimer&apos s Disease Bioinformatics Brain Brain Diseases Brain region Candidate Disease Gene Cells Cognition Cognitive Cognitive deficits Cohort Studies DNA DNA Methylation DNA Methylation Regulation DNA Methyltransferase DNA Modification Methylases Dementia Deterioration Disease Elderly Epigenetic Process Evaluation Foundations Gene Expression Genes Genetic Hallmark Cell Hand Hippocampus (Brain)Impaired cognition Incidence Intervention Learning Light Longevity Measures Mediating Memory Methylation Molecular Mus Neurocognitive Neurodegenerative Disorders Neurons Pharmaceutical Preparations Process Protein Isoforms Public Health Regulation Reporting Research Risk Factors Sampling Sirolimus Solid Synapses Synaptic plasticity Testing Time Tissue Sample Tissues Work age related aged aging brain aging hippocampus base bisulfite brain cell brain tissue cognitive function effective therapy genome-wide histone modification human FRAP1 protein improved knock-down learning ability mTOR Signaling Pathway prevent public health relevance synaptic function tool

项目摘要

DESCRIPTION (provided by applicant): Age is the major risk factor for neurocognitive decline and dementia. Preventing and treating age-associated brain disorders will require elucidating the processes and mechanisms underlying normal brain aging and developing interventions that target such mechanisms. This project is based on the hypothesis that rapamycin retards brain aging by correcting age- associated aberrant DNA methylation regulation in the brain. The project tests one unique prediction of this hypothesis in aged mice treated with rapamycin compared with controls: Changes with age will be retarded by rapamycin in DNA methylations and the DNA methylation regulated genes important to synaptic and cognitive function in brain.

描述(申请人提供)：年龄是神经认知功能衰退和痴呆症的主要危险因素。预防和治疗与年龄相关的大脑疾病将需要阐明正常大脑衰老的过程和机制，并开发针对这些机制的干预措施。该项目基于这样的假设，即雷帕霉素通过纠正大脑中与年龄相关的异常DNA甲基化调节来延缓大脑衰老。与对照组相比，该项目在接受雷帕霉素治疗的老年小鼠中测试了这一假说的一个独特预测：在DNA甲基化和对大脑突触和认知功能重要的DNA甲基化调节基因中，雷帕霉素将延缓随年龄的变化。