Mitochondria-targeted antioxidant supplementation for improving age-related vascular dysfunction in older adults
Description: CANDIDATE: Dr. Kevin Murray is a postdoctoral fellow in Integrative Physiology at the University of Colorado Boulder. He seeks to conduct research evaluating the efficacy of chronic oral supplementation with MitoQ to improve vascular function in older adults (over 60 yrs). His long-term goal is to acquire the research and professional skills to become an extramurally funded scientist investigating intervention strategies to improve vascular function and cardiovascular disease (CVD) risk with aging. CAREER DEVELOPMENT PLAN: 1) Learn new experimental skills (direct a clinical trial; assess vascular function; ex vivo cell culture); 2) continue biostatistical training; 3) enhance professional development skills; attend/present at weekly journal clubs, seminar, and scientific meetings; and regular interactions with the mentoring team. ENVIRONMENT: The environment for Dr. Murray’s training is exceptional. The sponsor, Dr. Seals, is an internationally recognized, NIH-funded scientist with a strong record of successful mentoring in interventions that improve vascular function with aging. Co-sponsor, Dr. Rossman, is an NIH-funded investigator with expertise in vascular aging and MitoQ treatment in older adults. Dr. You and Dr. Chonchol are long-time collaborators of Drs. Seals and Rossman. RESEARCH PLAN: Aging is the primary CVD risk factor and age-associated CVD is largely mediated by vascular dysfunction characterized by endothelial dysfunction and large elastic artery stiffening. Excess production of mitochondrial reactive oxygen species (mtROS) is a major driver of vascular dysfunction with aging. MitoQ is a mitochondria-targeted antioxidant that accumulates in the mitochondrial inner membrane. Chronic oral treatment with MitoQ in old mice and in a pilot trial of older adults improved endothelial function and reduced arterial stiffness. Initial assessments suggest reduced mtROS and changes in circulating oxidized low-density lipoprotein are mechanisms for the improvements in endothelial function with MitoQ. I will leverage my Sponsor’s new NIH-R01 funded phase IIa randomized, placebo-controlled, double-blind, parallel-group design clinical trial as a training vehicle to determine the efficacy of MitoQ to improve endothelial dysfunction (Aim 1), determine the mechanisms by which MitoQ improves vascular function via innovative in vivo and ex vivo approaches (Aim 2), and assess the effect of MitoQ supplementation on arterial stiffness (Aim 3) in older adults.
Funder: American Heart Association
Amount: $140,600
Funding type: fellowship
Funder scheme: Postdoctoral Fellowship
Start date: 2023-01-01
End date: 2023-09-29
Investigators: Kevin Murray, Kevin Murray
Institution: University of Colorado Boulder
Funded outputs count: 7
Funder award ID: 23POST1025630
OpenAlex ID: G3199454763