Mitochondrial therapeutics for healthy brain aging

线粒体疗法促进大脑健康老化

• 批准号: 10259815
• 负责人: Ronald L Davis
• 金额: $ 15.28万
• 依托单位: SCRIPPS FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-10 至 2022-04-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259815
• 关键词: Abbreviations; Adult; Age; Aging; Algorithms; Anxiety; Behavior; Behavioral Assay; Biological Assay; Brain; Cardiovascular Diseases; Cell physiology; Chemicals; Chronic; Chronology; Clinical; Clinical Treatment; Cognition; Cognitive; Collection; Data; Dementia; Deterioration; Disease; Drug Screening; Elderly; Functional disorder; Future; Generations; Glaucoma; Goals; Health; Health Status; Human; Impairment; In Vitro; Laboratory Animals; Lead; Learning; Length; Libraries; Literature; Malignant Neoplasms; Measures; Memory; Mental Depression; Mental Health; Metabolic; Mitochondria; Modeling; Mus; Neurons; Non-Insulin-Dependent Diabetes Mellitus; Organelles; Organism; Osteoporosis; Parents; Penetration; Pharmaceutical Preparations; Phase; Pilot Projects; Population; Prevention; Property; Recording of previous events; Research; Risk Factors; Sampling; Shapes; Structure; System; Testing; Therapeutic; Time; Triage; age effect; age related; aged; aging brain; analog; base; body system; brain health; drug discovery; drug metabolism; functional decline; human disease; improved; in vitro Assay; in vivo; in vivo evaluation; lead optimization; middle age; mitochondrial dysfunction; novel; novel therapeutics; research and development; response; screening; small molecule; small molecule therapeutics; success

There is a pressing need to develop therapeutics that can promote brain health with aging. Such therapeutics would postpone the deterioration in cognition and mental health that occurs with age. The proposed research will identify, optimize, and then test in laboratory animals such therapeutics as steps towards future clinical use. The research focus is on mitochondria, the organelle in brain neurons that provides energy and many other functions for neurons to function and remain healthy. Mitochondria become impaired with age; mitochondrial impairment is one of the well-known hallmarks of aging. In pilot studies, we have identified a few new drugs that have the potential to enhance mitochondrial function across age. We will search for and identify five times more to enlarge the set of potential “mitotherapeutics.” These drugs will then be tested in laboratory animals to determine whether they can protect mitochondria from the insults associated with age and enhance brain function; postponing or eliminating the cognitive and mental health issues that occur with age. Drugs with the potential to postpone or eliminate these issues would have an enormous impact on brain health for the late adult and elderly in the U.S. population.

迫切需要开发可以随着衰老而促进大脑健康的治疗。这种疗法 会推迟随着年龄的增长而发生的认知和心理健康的定义。拟议的研究 将识别，优化，然后在实验室动物中进行测试，例如迈向未来临床的步骤 使用。研究重点是线粒体，线粒体是脑神经元中的细胞器，可提供能量和许多 神经元功能并保持健康的其他功能。线粒体随着年龄的增长而受到损害。 线粒体损伤是衰老的著名标志之一。在试点研究中，我们已经确定了一些 有可能增强跨年龄范围的线粒体功能的新药。我们将搜索并确定 增加了五倍以扩大潜在的“丝质治疗”。这些药物将在实验室中进行测试 动物以确定它们是否可以保护线粒体免受与年龄相关的侮辱并增强 大脑功能；推迟或消除随着年龄的增长而发生的认知和心理健康问题。毒品与 推迟或消除这些问题的潜力将对晚期对大脑健康产生增强的影响 在美国人口中成人和年龄较大。