The microvasculature is critical for the control of blood flow and tissue perfusion. Compromised microvascular function occurs during aging as well as several disease states including diabetes and peripheral arterial disease and may contribute to compromised muscle performance within these populations. Unfortunately, practical measures for assessing microvascular function are lacking. With the advent of muscle functional magnetic resonance imaging (fMRI) using blood oxygen level- dependent imaging (BOLD), peripheral microvascular function can be assessed noninvasively. Our studies have shown that muscle BOLD responses are sensitive to blood volume and oxygenation changes and are increased in magnitude in young endurance trained adults when compared to sedentary adults. Preliminary data also suggest an age related decline in BOLD responses and slowing of muscle oxygen kinetics. A reduced BOLD response is important because it indicates reduced muscle perfusion which impacts muscle metabolism and muscle function. The overall purpose of these studies is to exploit muscle BOLD to assess microvascular function in elderly adults. In addition, these studies will also contribute to the understanding of the bioenergetic consequences of aging.
Aim 1 will examine the effect of age on muscle BOLD by comparing single contraction mediated responses in young versus elderly adults. We will also examine the effect of age on phosphocreatine (PCr) recovery kinetics;PCr kinetics reflect oxidative ATP synthesis. These outcomes together will allow us to integrate microvascular function with oxygen consumption and ATP synthesis.
Aim 2 will examine the influence of aerobic exercise on the muscle BOLD response in sedentary elderly adults. Echo planar fMRI will be used to acquire muscle BOLD images;phosphorus spectroscopy will be used to evaluate PCr kinetics. Muscle BOLD is an important measure because it reflects muscle perfusion and we suggest this is a critical parameter that is lost with aging. Imbalances between perfusion and metabolism may contribute to age related muscle impairment. Our proposed studies are consistent with an emerging consensus that the initial vascular responses are pivotal in vascular control and function. These studies will provide a strong foundation for a noninvasive assessment tool that evaluates microvascular function and will show the ability of aerobic exercise to improve microvascular function in elderly adults. As the U.S. older adult population is nearly 50 million strong and growing, understanding the factors related to poor physical function is imperative. Our long-term goal is to establish noninvasive methods for assessing microvascular and muscle function that can be used in vascular and muscle disease detection and monitoring.

Public Health Relevance

Peripheral vascular function declines with age and may contribute to reduced muscle performance and activity limitations in aging. The function of the small blood vessels within the muscle is likely to play a role in age related functional declines. The proposed studies will evaluate a new noninvasive method for measuring microvascular function and examine the influence of aerobic exercise training on microvascular function in aging.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AG042041-01
Application #
8284589
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Joseph, Lyndon
Project Start
2012-04-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
1
Fiscal Year
2012
Total Cost
$230,250
Indirect Cost
$80,250
Name
Michigan State University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Osteopathic Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824