Physical capacity and muscular function are reduced with aging. Age-associated reduction 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. This is supported by the observation that pulmonary gas exchange dynamics are slowed with advancing age and it is now recognized that these changes are driven by impaired muscle oxygen exchange and result in elevated metabolic perturbations within contracting muscle that limit exercise tolerance. To date, however, key structural and functional relationships within young and aged skeletal muscle remain obscure. Dr. Delp's lab has assembled a unique combination of established and state-of-the art techniques to address this problem. I plan to test the broad hypothesis that aging induces microcirculatory dysfunction that impairs oxygen transport. This work will utilize the rat model of aging, a widely accepted analog of the human condition that has the major advantage of permitting very invasive studies. 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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AG025622-01A2
Application #
7113456
Study Section
Special Emphasis Panel (ZRG1-F10-H (20))
Program Officer
Kohanski, Ronald A
Project Start
2006-04-01
Project End
2009-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
1
Fiscal Year
2006
Total Cost
$45,976
Indirect Cost
Name
West Virginia University
Department
Physiology
Type
Schools of Medicine
DUNS #
191510239
City
Morgantown
State
WV
Country
United States
Zip Code
26506
Delp, Michael D; Behnke, Bradley J; Spier, Scott A et al. (2008) Ageing diminishes endothelium-dependent vasodilatation and tetrahydrobiopterin content in rat skeletal muscle arterioles. J Physiol 586:1161-8
Behnke, Bradley J; Zawieja, David C; Gashev, Anatoliy A et al. (2008) Diminished mesenteric vaso- and venoconstriction and elevated plasma ANP and BNP with simulated microgravity. J Appl Physiol 104:1273-80
Colleran, Patrick N; Behnke, Bradley J; Wilkerson, M Keith et al. (2008) Simulated microgravity alters rat mesenteric artery vasoconstrictor dynamics through an intracellular Ca(2+) release mechanism. Am J Physiol Regul Integr Comp Physiol 294:R1577-85
Prisby, Rhonda D; Ramsey, Michael W; Behnke, Brad J et al. (2007) Aging reduces skeletal blood flow, endothelium-dependent vasodilation, and NO bioavailability in rats. J Bone Miner Res 22:1280-8
Ramsey, Michael W; Behnke, Bradley J; Prisby, Rhonda D et al. (2007) Effects of aging on adipose resistance artery vasoconstriction: possible implications for orthostatic blood pressure regulation. J Appl Physiol 103:1636-43
Behnke, Bradley J; Delp, Michael D; Poole, David C et al. (2007) Aging potentiates the effect of congestive heart failure on muscle microvascular oxygenation. J Appl Physiol 103:1757-63
Behnke, Bradley J; Prisby, Rhonda D; Lesniewski, Lisa A et al. (2006) Influence of ageing and physical activity on vascular morphology in rat skeletal muscle. J Physiol 575:617-26