Exerkines and the Heterogeneity of Peripheral and Cerebral Vascular Adaptations to Exercise Training With Aging in Women and Men
University of Colorado, Denver
Summary
The goal of the proposed study is to understand the reasons for the variability in aerobic exercise (AE) training benefits on the vasculature in middle-age and older (MA/O) adults, including differences between men and women. To achieve this goal, a mechanistic randomized controlled (RCT) will be conducted, in which adults are randomized to 12-weeks intervention of AE or no-exercise Control. Our overall hypothesis is that the exercise response variation in vascular benefits is related to age and sex differences in the biological changes underlying vascular aging and/or the molecular transducers (i.e., circulating molecules) that communicate and coordinate the effects of AE on the vasculature in the periphery and brain. Because this is a mechanistic trial, the overall goal is not a single health-related outcome. Rather, the goal is to advance our understanding of the molecular signals and pathways underlying the systemic and local effects of AE on vascular health that may explain the variability in AE responses with age and sex. This knowledge will allow for the development of personalized age- and sex-specific AE recommendations, and/or provide insights into molecular targets that can be manipulated to enhance and/or mimic exercise in non-responders or in persons unable to exercise.
Description
This is a single-blind (investigator and outcomes assessor), parallel-design clinical trial to determine whether heterogeneity in the biology of aging and molecular transducers with acute and chronic AE mediates AE response variation in peripheral endothelial function (brachial artery flow-mediated dilation \[FMD\]; primary outcome) and cerebrovascular function (cerebrovascular reactivity to a hypercapnic stimulus \[CVRCO2\]; primary outcome) with age and between sexes. Biospecimens (blood, vascular endothelial cells) obtained: (a) before, during (blood only), and 0.25, 0.5 and 2 h (blood only…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * Ability to provide consent; * Man or woman \>= 18 years; * Willing to be randomized to an exercise or control intervention; * No orthopedic limitations that would prevent the volunteer from performing treadmill or cycling exercise; * No use of hormone therapy in postmenopausal women or in men (note, hormonal contraceptives in premenopausal women will be allowed); * Healthy, as determined by medical history, physical examination, standard blood chemistries and ECG at rest and during a physician monitored graded exercise treadmill test; * Sedentary or recreationally active…
Interventions
- BehavioralAerobic Exercise Training
The aerobic exercise training intervention will consist of moderate-intensity aerobic exercise training program consisting of treadmill walking/running and upright cycling. The training program involves 3 training sessions per week for 12 weeks. Each session will be ≈ 60 minutes in duration.
Location
- University of Colorado Anschutz Medical Center, Clinical Translational Research Center and Exercise Research LaboratoryAurora, Colorado