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

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2022 · $580,039

## Abstract

Project Summary
 The vast majority of cardiovascular diseases (CVD) occur in men and women ≥60 years of age. Changes
in the demographics of aging in the U.S. predict progressive increases in CVD without effective intervention.
Vascular dysfunction, including endothelial dysfunction as assessed by reduced endothelium-dependent
dilation (EDD) and stiffening of the large elastic arteries (i.e., aortic and carotid artery stiffening), is a major
mechanism of increased risk of CVD in older adults. Excess production of reactive oxygen species by
mitochondria (mtROS) has emerged as a central feature of vascular oxidative stress with aging and driver of
age-related vascular dysfunction. As such, identifying novel strategies to decrease mtROS and improve
vascular function, to ultimately reduce the risk of age-related CVD, is an important biomedical objective.
 MitoQ is a mitochondria-targeted antioxidant that accumulates at the inner mitochondrial membrane where
it is optimally positioned to reduce mtROS. Preclinical findings from our laboratory showed that 4 weeks of
oral MitoQ supplementation completely restored EDD in old mice, ameliorated mtROS-associated
suppression of EDD, and was associated with reduced arterial mtROS, oxidative stress and improved
mitochondrial health. MitoQ therapy also reduced aortic stiffness in old mice. We recently took the first step
in translating these findings in a small pilot study of older adults (n=20). We found that supplementation with
MitoQ was well-tolerated, improved endothelial function and reduced plasma levels of oxidized low-density
lipoprotein, a circulating biomarker of oxidative stress. Consistent with our preclinical findings, preliminary
mechanistic assessments in subsets of our subjects suggest that improved endothelial function with MitoQ is
mediated by reduced endothelial cell mtROS production, associated reductions in tonic mtROS-related
suppression of EDD, and improved mitochondrial health, linked in part to changes in circulating factors in
the serum induced by chronic MitoQ supplementation. Lastly, MitoQ reduced aortic stiffness in older adults
who exhibited age-related aortic stiffening at baseline.
 Here we propose a randomized, placebo-controlled, double-blind clinical trial (PA-19-055) to establish
oral MitoQ (20 mg/day; MitoQ, Ltd.) for 6 months vs. placebo (n=56/group) for improving endothelial function in
older men and women (≥60 years), and determine the mechanisms by which MitoQ improves endothelial
function. We also propose to assess the effect of MitoQ on arterial stiffness.
Hypothesis 1: Oral MitoQ supplementation will improve vascular endothelial function in healthy older adults.
Hypothesis 2: Improvements in endothelial function with oral MitoQ supplementation in older adults will be
mediated by reduced mtROS-related suppression of EDD and associated with reduced endothelial cell ROS
production, vascular and systemic oxidative stress, and improved endothelial markers of mitochondrial h...

## Key facts

- **NIH application ID:** 10319609
- **Project number:** 5R01AG066730-02
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** DOUGLAS R SEALS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $580,039
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10319609

## Citation

> US National Institutes of Health, RePORTER application 10319609, Mitochondrial-targeted antioxidant supplementation for improving age-related vascular dysfunction in humans (5R01AG066730-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10319609. Licensed CC0.

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