The Mito-Frail Trial: Effects of MitoQ on Vasodilation, Mobility and Cognitive Performance in Frail Older Adults

Mito-Frail 试验：MitoQ 对体弱老年人的血管舒张、活动能力和认知能力的影响

• 批准号: 10572663
• 负责人: Oh Sung Kwon
• 金额: $ 13.45万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-15 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10572663
• 关键词: Address; Adult; Aging; Agreement; Alzheimer' s Disease; Animal Model; Antioxidants; Atherosclerosis; Attenuated; Biological; Biological Aging; Biological Availability; Biological Markers; Blood Flow Velocity; Blood Vessels; Brain; Cardiovascular Diseases; Cardiovascular Physiology; Cerebrovascular system; Cerebrum; Chronic; Chronic Disease; Clinical; Clinical Trials; Cognitive; Collaborations; Custom; Data; Dementia; Disease; Elderly; Endothelium; Exercise; Exercise Physiology; Frail Elderly; Funding; Future; Gait speed; Geroscience; Goals; Homeostasis; Human Resources; Hypertension; Impairment; Individual; Learning; Longevity; Measurement; Measures; Mediating; Memory; Metabolic; Mitochondria; Morbidity - disease rate; Multi-Institutional Clinical Trial; Nitric Oxide; Perfusion; Peripheral; Phase; Physical Function; Physical Performance; Physiological; Play; Quality of life; Reactive Oxygen Species; Regulation; Research; Research Design; Research Personnel; Research Training; Risk; Risk Factors; Role; Science; Site; Source; Supplementation; Time; Training; Training and Education; Trust; United States National Institutes of Health; Vascular Dementia; Vascular Endothelium; Vasodilation; Walking; cardiovascular risk factor; cerebral hypoperfusion; cerebrovascular; cognitive enhancement; cognitive function; cognitive performance; design; disability; effective intervention; effective therapy; experience; functional independence; functional outcomes; high risk; improved; investigator training; middle cerebral artery; mild cognitive impairment; mortality; multidisciplinary; novel therapeutic intervention; peripheral blood vessel; prevent; response; skills; walker; walking speed; Address; Adult; Aging; Agreement; Alzheimer' s Disease; Animal Model; Antioxidants; Atherosclerosis; Attenuated; Biological; Biological Aging; Biological Availability; Biological Markers; Blood Flow Velocity; Blood Vessels; Brain; Cardiovascular Diseases; Cardiovascular Physiology; Cerebrovascular system; Cerebrum; Chronic; Chronic Disease; Clinical; Clinical Trials; Cognitive; Collaborations; Custom; Data; Dementia; Disease; Elderly; Endothelium; Exercise; Exercise Physiology; Frail Elderly; Funding; Future; Gait speed; Geroscience; Goals; Homeostasis; Human Resources; Hypertension; Impairment; Individual; Learning; Longevity; Measurement; Measures; Mediating; Memory; Metabolic; Mitochondria; Morbidity - disease rate; Multi-Institutional Clinical Trial; Nitric Oxide; Perfusion; Peripheral; Phase; Physical Function; Physical Performance; Physiological; Play; Quality of life; Reactive Oxygen Species; Regulation; Research; Research Design; Research Personnel; Research Training; Risk; Risk Factors; Role; Science; Site; Source; Supplementation; Time; Training; Training and Education; Trust; United States National Institutes of Health; Vascular Dementia; Vascular Endothelium; Vasodilation; Walking; cardiovascular risk factor; cerebral hypoperfusion; cerebrovascular; cognitive enhancement; cognitive function; cognitive performance; design; disability; effective intervention; effective therapy; experience; functional independence; functional outcomes; high risk; improved; investigator training; middle cerebral artery; mild cognitive impairment; mortality; multidisciplinary; novel therapeutic intervention; peripheral blood vessel; prevent; response; skills; walker; walking speed

PROJECT SUMMARY The overarching goal of this proposal is to provide the applicant with selected additional skills required for an applicant to become an independent NIH-funded investigator capable of designing and implementing early phase geroscience-guided clinical trials that have the potential to extend healthy lifespan by targeting biological aging. This custom-designed learning experience will be enhanced by three unique components. First, a Patterson Trust-funded study “The Mito-Frail Trial: Effects of MitoQ on Vasodilation, Mobility and Cognitive Performance in Frail Older Adults” will provide a research platform. Second, the NIA Translational Geroscience Network (R33 AG061456) and its Facility for Geroscience Analysis has agreed to provide learning experiences and subsidized measurements of biomarkers permitting a much broader and deeper analysis of biological hallmarks of aging. Third, the NIA Geroscience Education and Training Network (R25 AG073119) will permit the candidate to fulfill the requirements for a Certificate in Geroscience at UConn, one of the network's current five sites. Chronic diseases and associated declines in physical and cognitive performance contribute greatly to lost independence with aging. In addition to a lack of effective interventions other than exercise to address either problem, few studies have examined strategies for targeting both conditions in frail individuals who may experience difficulties with both walking and memory. Use of geroscience-guided therapies permits us to target mechanisms shared by aging with chronic conditions for which aging represents a major risk factor. Thus, instead of focusing on one single disease at a time, it may be possible to delay the onset and progression of disability involving multiple functional domains including those caused by Alzheimer's disease and other dementias. We have recently shown that MitoQ, a mitochondria-targeted antioxidant known to improve endothelial function and Nitric Oxide (NO) bioavailability, may also restore impaired flow-mediated vasodilation in frail older adults, enhancing gait speed. In the Mito-Frail study we now wish to explore the hypothesis that MitoQ attenuates aging- related declines in flow-mediated vasodilation involving both peripheral and cerebral blood vessels. At the same time, we will obtain feasibility and pilot data involving measures of physical mobility and cognitive performance that may help us design and power a future clinical trial. Ultimately, we seek to develop strategies for preventing or slowing the progression of Alzheimer's disease and the vascular contribution to dementia. Therefore, Aim 1 will assess peripheral and cerebral NO bioavailability and mitochondrial reactive oxygen species (mtROS) levels in older adults who are healthy, others who are frail with slow walking speed and those who meet criteria for mild cognitive impairment (MCI). Aim 2 will determine whether MitoQ supplementation can improve vasodilation with enhancing cognitive function. The proposed research will provide essential training for the candidate who will establish expertise as an independent NIA-funded investigator conducting cutting-edge translational geroscience research designed to maintain and enhance functional independence in older adults.

项目摘要 该提案的总体目标是为适用 申请人成为一名能够设计和实施早期阶段的独立NIH资助的研究者 Geroscience引导的临床试验具有通过靶向生物衰老来延长健康寿命的潜力。 这种定制设计的学习体验将通过三个独特的组成部分来增强。首先，帕特森 信任资助的研究“ MITO-FRAIL试验：Mitoq对血管舒张，活动性和认知性能的影响 在脆弱的老年人中”将提供一个研究平台。其次，NIA转化Geroscience网络（R33 AG061456）及其用于Geroscience分析的设施已同意提供学习经验并提供补贴 生物标志物的测量允许对衰老的生物学标志进行更广泛，更深入的分析。 第三，NIA GEROSCIENCE教育和培训网络（R25 AG073119）将允许候选人履行 网络当前五个站点之一UConn的Geroscience证书的要求。 慢性疾病和相关的身体和认知表现下降都对失落造成了很大的贡献 与老化的独立性。除了锻炼以外的缺乏有效的干预措施以解决 问题，很少有研究研究了针对脆弱个人的两种情况的策略， 步行和记忆都会遇到困难。使用Geroscience引导的疗法可以使我们靶向 衰老分享的机制是衰老代表主要危险因素的慢性疾病。相反 一次专注于一种疾病，可能会延迟残疾的发作和进展 涉及多个功能领域，包括由阿尔茨海默氏病和其他痴呆症引起的。 我们最近表明，Mitoq是一种已知可改善内皮功能的线粒体靶向抗氧化剂 和一氧化氮（NO）生物利用度，还可能恢复流动介导的血管舒张受损，在脆弱的老年人中， 提高步态速度。在MITO-FRAIL研究中，我们现在希望探讨Mitoq减弱衰老的假设 相关的流动介导的血管舒张下降，涉及外周和脑血管。同样 时间，我们将获得可行性和试验数据，涉及物理流动性和认知性能的测量 这可能有助于我们设计和为未来的临床试验提供动力。最终，我们试图制定防止的策略 或减慢阿尔茨海默氏病的进展和对痴呆症的血管贡献。 因此，AIM 1将评估外周和脑无生物利用度和线粒体活性氧 健康健康的老年人中的物种（MTROS）水平 符合轻度认知障碍标准（MCI）。 AIM 2将确定补充MITOQ是否可以 通过增强认知功能改善血管舒张。拟议的研究将为 将建立专业知识的候选人作为独立的NIA资助的调查员进行尖端 转化的Geroscience研究旨在维持和增强老年人的功能独立性。