NCT06912984

Heterogeneity of Vascular Adaptations to Exercise With Aging in Women and Men

Exerkines and the Heterogeneity of Peripheral and Cerebral Vascular Adaptations to Exercise Training With Aging in Women and Men

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 242 (estimated)
• Sponsor: University of Colorado, Denver · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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.

Detailed 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) after acute treadmill AE (60-80% VO2max, 40 minutes); (b) before and after a 12-week AE intervention (3 d/week, 60-80% heart rate reserve, \~1 h duration); (c) or non-exercise control will be assayed for transcriptomic (mRNA transcripts), proteomic, metabolomic (small metabolites) and EMVs and their cargo (e.g., microRNA) in sex balanced groups of young (18-39 years), middle-aged (40-59 years) and older (≥60 years) adults. There is also collection of cardiorespiratory fitness, blood pressure, body composition (measured by dual-energy x-ray absorptiometry), physical activity and sleep using wearable devices, and health status questionnaires.

Conditions

• Aging
• Physical Activity
• Vascular Health

Interventions

Type	Name	Description
BEHAVIORAL	Aerobic 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.

Timeline

• Start date: 2025-05-28
• Primary completion: 2029-07-31
• Completion: 2029-07-31
• First posted: 2025-04-06
• Last updated: 2025-06-05

Locations

1 site across 1 country: United States