Physical capacity and muscular function are reduced with aging. Age-associated reductions in muscle blood flow and its intravascular distribution within and between skeletal muscles is thought to be linked mechanistically to muscle dysfunction in older individuals. To date, however, key structural and functional relationships within young and aged skeletal muscle remain obscure. Furthermore, as there is an age- associated increase in the percentage of adipose tissue, altered vasoreactivity in this tissue bed may affect whole body hemodynamics and skeletal muscle blood flow in the aged population. I plan to test the broad hypothesis that aging induces microcirculatory dysfunction (both structural and functional) that impairs oxygen transport, and exercise training can attenuate this microcircular dysfunction. This work will utilize the rat model of aging that is a widely accepted analog of the human condition that has the major advantage of permitting very invasive studies. The overall goal of this application is to provide me with new and complementary skills to become an independent researcher, and provide a foundation to launch my scientific career. In this regard each specific aim will allow me to master a novel technique to address the following in young, middle-aged, and old rats: 1) Elucidate the structural (e.g., vascular geometry), functional (e.g., endothelium-dependent vasodilation with tetrahydrobiopterin or L-arginine incubation), and molecular characteristics (e.g., eNOS mRNA and protein expressions) of skeletal muscle and adipose tissue resistance vessels via the isolated microvessel technique, 2) Examine alterations in skeletal muscle vasculature resulting from prolonged exercise training, 3) Transiently alter eNOS, VEGF or GTP cyclohydrolase mRNA and protein expression via adenovirus gene therapy, and 4) Determine whether detremints in adipose tissue vasoreactivity with age may contrribute to reduce skeletal muscle blood flow during exercise. Development of effective strategies to attenuate the deleterious effects of aging on physical capacity is contingent upon resolution of the mechanistic bases for muscle dysfunction in this population. In this regard, these specific aims seek to address several important potential mechanisms for the physical limitations in senescent individuals, and provide the basis for future research and funding to initiate an independent career.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Scientist Development Award - Research & Training (K01)
Project #
Application #
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Kohanski, Ronald A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Florida
Schools of Allied Health Profes
United States
Zip Code
Stabley, John N; Prisby, Rhonda D; Behnke, Bradley J et al. (2015) Type 2 diabetes alters bone and marrow blood flow and vascular control mechanisms in the ZDF rat. J Endocrinol 225:47-58
Stabley, John N; Moningka, Natasha C; Behnke, Bradley J et al. (2014) Exercise training augments regional bone and marrow blood flow during exercise. Med Sci Sports Exerc 46:2107-12
Joseph, A-M; Nguyen, L M-D; Welter, A E et al. (2014) Mitochondrial adaptations evoked with exercise are associated with a reduction in age-induced testicular atrophy in Fischer-344 rats. Biogerontology 15:517-534
Stabley, John N; Prisby, Rhonda D; Behnke, Bradley J et al. (2013) Chronic skeletal unloading of the rat femur: mechanisms and functional consequences of vascular remodeling. Bone 57:355-60
McDonough, Paul; Padilla, Danielle J; Kano, Yutaka et al. (2012) Plasticity of microvascular oxygenation control in rat fast-twitch muscle: effects of experimental creatine depletion. Respir Physiol Neurobiol 181:14-20
Davis 3rd, Robert T; Bruells, Christian S; Stabley, John N et al. (2012) Mechanical ventilation reduces rat diaphragm blood flow and impairs oxygen delivery and uptake. Crit Care Med 40:2858-66
Park, Yoonjung; Prisby, Rhonda D; Behnke, Brad J et al. (2012) Effects of aging, TNF-?, and exercise training on angiotensin II-induced vasoconstriction of rat skeletal muscle arterioles. J Appl Physiol (1985) 113:1091-100
Behnke, Bradley J; Delp, Michael D (2010) Aging blunts the dynamics of vasodilation in isolated skeletal muscle resistance vessels. J Appl Physiol 108:14-20
Behnke, Brad J; Ferreira, Leonardo F; McDonough, P J et al. (2009) Recovery dynamics of skeletal muscle oxygen uptake during the exercise off-transient. Respir Physiol Neurobiol 168:254-60