Cellular senescence and cell fate/interactions as drivers of Alzheimer's and age-related dementias

细胞衰老和细胞命运/相互作用是阿尔茨海默氏症和年龄相关性痴呆的驱动因素

基本信息

批准号：
10853797
负责人：
Judith Campisi
金额：
$ 11.14万
依托单位：
BUCK INSTITUTE FOR RESEARCH ON AGING
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-30 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10853797
关键词：
3-Dimensional Affect Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease related dementia Applications Grants Astrocytes Automobile Driving Bioinformatics Brain Cell Aging Cell Communication Cell Culture Techniques Cell Death Cells Clinical Cognition Collaborations Data Dementia Development Disease Disease Progression Economics Emotional Endothelial Cells Etiology Family Goals Head Human Inflammation Intervention Knowledge Macrophage Metabolic Metabolism Modeling Molecular Mus Nature Nerve Degeneration Neurodegenerative Disorders Neuroglia Neurons Oligodendroglia Organoids Pathology Patients Pharmaceutical Preparations Phenotype Population Productivity Program Research Project Grants Proteome Proteomics Publishing Recording of previous events Research Research Personnel Research Project Grants Risk Risk Factors Role Testing Time Translating age related age related neurodegeneration aging brain brain cell cell type cost effective intervention effective therapy induced pluripotent stem cell insight interest member metabolome mouse model novel novel strategies programs response senescence social transcriptomics

项目摘要

OVERALL PROJECT SUMMARY Aging is by far the most important driver and risk factor for developing a variety of neurodegenerative diseases, including Alzheimer’s disease (AD) and related dementias. These devastating diseases exact an enormous emotional, social and economic toll on patients and their families, yet to date there are no effective treatments that delay, much less reverse, the onset or progression of these diseases. Clearly, new approaches to understanding and treating age-related neurodegeneration are needed. This Program Project Grant (PPG) proposal aims to fill this serious gap in our knowledge and treatment approaches. The proposed PPG consists of three research projects, each focused on an aspect of brain aging that is known to be crucial for brain function: 1) cell fate decisions, particularly cell death and cellular senescence; 2) metabolism, particularly responses leading to metabolic reprogramming and inflammation; and 3) cell-cell interactions, particularly interactions between neurons and non-neuronal cells in the brain. We propose to support the projects by an administrative core, which will also provide statistical and bioinformatics support, and three scientific cores: 1) an iPSC/Organoid core; 2) a Proteomics and Metabolism core; and 3) a Single Cell and Spatial Transcriptomics core. The PPG benefits from the exceptionally diverse expertise of the Project and Core leaders and co-leaders, all of whom are acknowledged leaders in contemporary aging research. Each of the projects is a close collaboration among several PPG members, many of whom have a history of productive collaboration. Each of the scientific cores will provide state-of-the art support to the projects, enabling conceptual and technical advances that would be difficult to achieve in isolation. Together, the Projects and Cores have the potential to uncover new mechanisms of AD and related dementias, which will be tested in human cells and organoids and mice. Importantly, these mechanisms can be developed into interventions that can be used treat human patients.

项目总体概要迄今为止，衰老是各种神经退行性疾病最重要的驱动因素和风险因素疾病，包括阿尔茨海默氏病 (AD) 和相关的痴呆症，这些破坏性疾病会导致严重的后果。给患者及其家人带来巨大的情感、社会和经济损失，但迄今为止尚无有效的治疗方法显然，新方法可以延缓（更不用说逆转）这些疾病的发作或进展。需要了解和治疗与年龄相关的神经退行性疾病。提案旨在填补我们的知识和治疗方法中的这一严重空白。三个研究项目，每个项目都专注于已知对大脑功能至关重要的大脑衰老的一个方面： 1) 细胞命运决定，特别是细胞死亡和细胞衰老 2) 新陈代谢，特别是反应；导致代谢重编程和炎症；3) 细胞间相互作用，特别是相互作用我们建议由行政人员支持这些项目。核心，还将提供统计和生物信息学支持，以及三个科学核心：1） iPSC/类器官核心；2) 蛋白质组学和代谢核心；3) 单细胞和空间转录组学 PPG 受益于项目和核心领导者和联合领导者极其多样化的专业知识，他们都是当代衰老研究领域公认的领导者，每个项目都是一个封闭的项目。多个 PPG 成员之间的合作，其中许多成员都有富有成效的合作历史。科学核心将为项目提供最先进的支持，使概念和技术这些项目和核心有潜力共同实现这些进步。揭示 AD 和相关痴呆症的新机制，将在人体细胞和类器官中进行测试重要的是，这些机制可以发展成可用于治疗人类患者的干预措施。