# Mitochondrial-targeted antioxidant supplementation for improving age-related vascular dysfunction in humans

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2024 · $354,164

## Abstract

PROJECT SUMMARY
Aging is the primary risk factor for mild cognitive impairment (MCI), Alzheimer’s disease and related
dementias. Cerebrovascular dysfunction (i.e., reduced cerebrovascular reactivity and cerebral blood flow) is
a key mechanism contributing to the increase in risk with aging and is largely mediated by decreases in the
vasodilatory molecule nitric oxide (NO), leading to impaired cerebrovascular dilation. Excessive reactive
oxygen species production by mitochondria (mtROS) is a major contributor to cerebrovascular dysfunction
as mtROS can reduce bioavailable NO and impair cerebral endothelial cell (EC) function. Because the aging
population and prevalence of MCI and dementias are projected to increase in coming years, establishing novel
strategies to decrease mtROS to improve cognitive and cerebrovascular function in older adults is an
important biomedical research goal to reduce the risk of MCI, Alzheimer’s disease and related dementias.
MitoQ is a mitochondrial-targeted antioxidant biochemically modified to accumulate in the inner mitochondrial
membrane where it is optimally positioned to reduce mtROS. We reported in an NIA R21-funded pilot clinical
trial that 6 weeks of MitoQ treatment in older adults improves peripheral vascular endothelial function
(brachial artery flow-mediated dilation) by reducing mtROS-related suppression of endothelial function.
We also found that MitoQ treatment-induced changes in the circulating milieu (plasma) evoke improvements in
human aortic EC function, as shown by higher acetylcholine-stimulated NO production and lower basal mtROS
bioactivity in ECs treated with plasma from subjects after MitoQ supplementation vs. placebo.
Our parent award is a larger, NIA R01-funded (AG067730) randomized, placebo-controlled clinical trial
assessing 3 months of MitoQ treatment for improving peripheral vascular function in older adults. To explore
the possible effects of MitoQ on cognitive and cerebrovascular function, we utilized subjects enrolled in the
parent trial to obtain preliminary data that suggest MitoQ treatment may improve fluid cognition (i.e., the
domain of cognition most heavily influenced by aging and Alzheimer’s disease) and cerebrovascular
function vs. placebo. We propose to leverage the R01-funded trial to determine the efficacy of MitoQ
supplementation for improving fluid cognition and cerebrovascular function in older adults and provide
insight into possible mechanism(s) contributing to these improvements. This research is highly relevant to
Alzheimer’s disease and related dementias as it will evaluate a novel clinical intervention for improving
cognitive and cerebrovascular function in asymptomatic older adults, a group disproportionately
burdened by MCI, Alzheimer’s disease and related dementias. Leveraging our ongoing clinical trial will
stimulate research in Alzheimer’s disease and related dementias by providing initial evidence for the efficacy
of dietary supplementation with MitoQ as an inn...

## Key facts

- **NIH application ID:** 10937681
- **Project number:** 3R01AG066730-04S1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** DOUGLAS R SEALS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $354,164
- **Award type:** 3
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10937681

## Citation

> US National Institutes of Health, RePORTER application 10937681, Mitochondrial-targeted antioxidant supplementation for improving age-related vascular dysfunction in humans (3R01AG066730-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10937681. Licensed CC0.

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