Even in healthy aging, there are many physiological changes. Advanced age is a major risk factor for coronary and peripheral vascular disease. Aging results in significant changes in skeletal muscle, among these is a lower capillary supply, known as capillary rarefaction. A lower skeletal muscle capillary supply is associated with reduced exercise tolerance and reduced insulin sensitivity, which are both risk factors for cardiovascular disease. In general, aging reduces the ability of the organism to respond to different types of stress. Advanced age is associated with a defect in compensatory neovascularization in response to tissue ischemia, possibly through a reduction in vascular endothelial growth factor (VEGF) expression. Recent work suggests that VEGF is important for skeletal muscle capillary maintenance and the angiogenic response to exercise training, a controlled stress that is known to increase VEGF expression. We therefore hypothesize that VEGF expression is lower in old humans. In addition, we hypothesize that in response to the stress of exercise, exercise-induced VEGF expression is reduced in aged humans. To test these hypotheses, we will determine the resting levels of skeletal muscle VEGF from skeletal muscle biopsies in three groups: 18-25 yrs; 45-55 yrs; and 60+ yrs of age. We will then exercise subjects at 50 percent of their maximum for 1 hr on a bicycle ergometer; an intensity and duration that we have shown to increase VEGF mRNA 5-6 fold in young subjects. Isolated mRNA will be analyzed by Northern blot analysis. Proteins will be analyzed by Western blot. Capillarization will be evaluated by morphometric analysis of muscle biopsy samples. Analysis of variance will be used to determine differences between groups and conditions. Data obtained from these studies will provide necessary information for future R01 funding. Findings will be important as little is known concerning the effects of aging on neovascularization potential in humans.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Academic Research Enhancement Awards (AREA) (R15)
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Geriatrics and Rehabilitation Medicine (GRM)
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Carrington, Jill L
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East Carolina University
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United States
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Gavin, Timothy P; Kraus, Raymond M; Carrithers, John A et al. (2015) Aging and the Skeletal Muscle Angiogenic Response to Exercise in Women. J Gerontol A Biol Sci Med Sci 70:1189-97
La Favor, Justin D; Kraus, Raymond M; Carrithers, Jonathan A et al. (2014) Sex differences with aging in nutritive skeletal muscle blood flow: impact of exercise training, nitric oxide, and ?-adrenergic-mediated mechanisms. Am J Physiol Heart Circ Physiol 307:H524-32
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Focht, Brian C; Knapp, Deborah J; Gavin, Timothy P et al. (2007) Affective and self-efficacy responses to acute aerobic exercise in sedentary older and younger adults. J Aging Phys Act 15:123-38
Ryan, Nicholas A; Zwetsloot, Kevin A; Westerkamp, Lenna M et al. (2006) Lower skeletal muscle capillarization and VEGF expression in aged vs. young men. J Appl Physiol 100:178-85
Gavin, T P; Westerkamp, L M; Zwetsloot, K A (2006) Soleus, plantaris and gastrocnemius VEGF mRNA responses to hypoxia and exercise are preserved in aged compared with young female C57BL/6 mice. Acta Physiol (Oxf) 188:113-21
Croley, Andrea N; Zwetsloot, Kevin A; Westerkamp, Lenna M et al. (2005) Lower capillarization, VEGF protein, and VEGF mRNA response to acute exercise in the vastus lateralis muscle of aged vs. young women. J Appl Physiol 99:1872-9

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