Assessing the Impact of Exercise-Induced Myokines on Neurovascular Coupling and Cognitive Function in Aging Adults

Project Abstract

This study investigates how exercise-induced myokines modulate neurovascular coupling (NVC) and cognitive function in aging adults, integrating molecular, physiological, and neuropsychological approaches to illuminate mechanisms linking physical activity to brain health. We hypothesize that regular aerobic and resistance training stimulate skeletal muscle to secrete myokines (e.g., irisin, BDNF, IL-6, myostatin) that cross the blood-brain barrier or act via systemic signaling to enhance cerebrovascular reactivity, cerebral blood flow regulation, and neurotrophic support, thereby improving cognitive domains susceptible to aging-related decline. A randomized controlled trial design will involve community-dwelling adults aged 65–80 assigned to a 24-week supervised exercise program (aerobic, resistance, or combined) or a non-exercise control, with equitable distribution of sex and baseline cognitive status. Primary outcomes include dynamic cerebral autoregulation and neurovascular coupling responses measured by transcranial Doppler ultrasound during cognitive tasks and hypercapnic challenges, complemented by arterial spin labeling MRI to quantify regional cerebral blood flow. Secondary outcomes encompass circulating myokine profiles (iris in, BDNF, irisin, IL-6, myostatin), inflammatory markers, insulin sensitivity, and body composition. Cognitive function will be assessed across memory, processing speed, executive function, and attention using a comprehensive neuropsychological battery, with longitudinal follow-ups at 3 and 6 months post-intervention to evaluate durability. Mechanistic sub-studies will examine skeletal muscle and peripheral blood mononuclear cell gene expression related to myokine signaling, endothelial function assays (flow-mediated dilation), and neuroimaging markers of brain structure (hippocampal volume) and function (functional connectivity within the default mode and frontoparietal networks). Data analysis will employ mixed-effects models to assess within- and between-group changes over time, mediation analyses to test whether myokine changes account for NVC and cognitive improvements, and dose-response relationships with exercise intensity and duration. We will stratify analyses by baseline age, sex, and vascular risk factors to identify subgroups with enhanced responsiveness. The study aims to (1) delineate the temporal sequence linking exercise, myokine secretion, cerebrovascular modulation, and cognitive gains; (2) identify the myokines most predictive of NVC and cognitive improvements; (3) determine whether combined aerobic-resistance programs yield superior neurovascular and cognitive benefits compared with single-modality training; and (4) establish practical exercise prescriptions that optimize brain vascular health in aging populations. Anticipated outcomes include demonstration of improved cerebrovascular reactivity and perfusion concurrent with favorable myokine profiles and enhanced performance in executive function and memory tasks, supporting exercise as a non-pharmacological strategy to mitigate age-related cognitive decline through myokine-mediated neurovascular mechanisms.

Project Overview

What This Project Is About

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This project looks at how exercise affects muscles release signals called myokines, and how these signals influence blood flow in the brain and thinking skills in older adults. It connects physical activity, brain blood flow (neurovascular coupling), and cognition in a simple, practical way.

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The Problem It Addresses

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As people age, brain blood flow and thinking abilities can decline. We don’t fully understand how regular exercise might help by changing myokine levels to support brain health. This project explores that possible link to identify strategies to protect or improve cognition in aging populations.

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Objectives of the Project

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1. Explain what myokines are and how they change with exercise.
2. Describe neurovascular coupling and its role in brain function.
3. Investigate how exercise-induced myokines might influence brain blood flow and cognition in older adults.
4. Review current research gaps and propose simple, testable ideas for future work.

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What You Will Do Step by Step

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1) Do a literature scan to gather existing evidence on myokines, neurovascular coupling, and cognition in aging. 2) Summarize key findings in plain language. 3) Develop a small, hypothetical study design or data analysis plan. 4) Explain how results could be measured and interpreted. 5) Highlight potential practical recommendations for exercise in older adults.

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Expected Outcome

Clear, easy-to-understand summary of how exercise could benefit brain blood flow and thinking in aging adults, along with identified knowledge gaps and practical suggestions for future research or activity guidelines.