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
基本信息
- 批准号:10572663
- 负责人:
- 金额:$ 13.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AddressAdultAgingAgreementAlzheimer&aposs DiseaseAnimal ModelAntioxidantsAtherosclerosisAttenuatedBiologicalBiological AgingBiological AvailabilityBiological MarkersBlood Flow VelocityBlood VesselsBrainCardiovascular DiseasesCardiovascular PhysiologyCerebrovascular systemCerebrumChronicChronic DiseaseClinicalClinical TrialsCognitiveCollaborationsCustomDataDementiaDiseaseElderlyEndotheliumExerciseExercise PhysiologyFrail ElderlyFundingFutureGait speedGeroscienceGoalsHomeostasisHuman ResourcesHypertensionImpairmentIndividualLearningLongevityMeasurementMeasuresMediatingMemoryMetabolicMitochondriaMorbidity - disease rateMulti-Institutional Clinical TrialNitric OxidePerfusionPeripheralPhasePhysical FunctionPhysical PerformancePhysiologicalPlayQuality of lifeReactive Oxygen SpeciesRegulationResearchResearch DesignResearch PersonnelResearch TrainingRiskRisk FactorsRoleScienceSiteSourceSupplementationTimeTrainingTraining and EducationTrustUnited States National Institutes of HealthVascular DementiaVascular EndotheliumVasodilationWalkingcardiovascular risk factorcerebral hypoperfusioncerebrovascularcognitive enhancementcognitive functioncognitive performancedesigndisabilityeffective interventioneffective therapyexperiencefunctional independencefunctional outcomeshigh riskimprovedinvestigator trainingmiddle cerebral arterymild cognitive impairmentmortalitymultidisciplinarynovel therapeutic interventionperipheral blood vesselpreventresponseskillswalkerwalking speed
项目摘要
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.
项目总结
项目成果
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