Our general hypothesis is that age-related decreases in skeletal muscle perfusion diminish the stimulus for anabolism in elderly muscle. Our preliminary results suggest that following a bolus ingestion of amino acids, elderly muscle protein synthesis is markedly delayed as compared to young. We hypothesize that in response to an increase in blood amino acid concentration, changes in interstitial fluid concentrations and muscle protein synthesis occur more sluggishly in the elderly. Further, we propose that these sluggish responses in elderly occur at least in part because of decreased muscle perfusion. We further hypothesize that exercise-induced increases in muscle blood flow, in the presence of amino acids, has an interactive effect on young and elderly skeletal muscle inducing an amplified anabolic response. The goal of this proposal is to determine the effects of increased muscle perfusion on muscle protein synthesis in elderly, either through aerobic exercise or peripheral vasodilation (femoral arterial infusion of sodium nitroprusside at 8 microg/min) both with and without amino acids. Further, we intend to utilize a novel 4-pool model of amino acid kinetics which allows for the determination of blood, intracellular and interstitial fluid amino acid concentrations. Moreover, we intend to use a novel contrast enhanced ultrasound technique to measure total leg blood flow (i.e. laser Doppler flowmetry) and microvascular perfusion (i.e. capillary flow and volume) in skeletal muscle. Muscle kinetics will be evaluated in response to a continuous infusion of amino acids under basal and increased blood flow conditions, in response to a bolus ingestion of amino acids under basal and increased blood flow conditions, and in response to 45 minutes of moderate aerobic exercise (45 min at 40 percent of VO2max), both with and without amino acid supplementation. Results from these studies will provide evidence as to the regulatory role of increased muscle perfusion, amino acid supplementation and aerobic exercise as means of improving skeletal muscle protein synthesis in the elderly.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
3R01AG021539-05S1
Application #
7930455
Study Section
Geriatrics and Rehabilitation Medicine (GRM)
Program Officer
Dutta, Chhanda
Project Start
2003-09-01
Project End
2011-05-31
Budget Start
2009-09-15
Budget End
2011-05-31
Support Year
5
Fiscal Year
2009
Total Cost
$289,679
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
Sheffield-Moore, Melinda; Wiktorowicz, John E; Soman, Kizhake V et al. (2013) Sildenafil increases muscle protein synthesis and reduces muscle fatigue. Clin Transl Sci 6:463-8
Dillon, E Lichar; Casperson, Shanon L; Durham, William J et al. (2011) Muscle protein metabolism responds similarly to exogenous amino acids in healthy younger and older adults during NO-induced hyperemia. Am J Physiol Regul Integr Comp Physiol 301:R1408-17
Tuvdendorj, Demidmaa; Chinkes, David L; Zhang, Xiao-Jun et al. (2011) Skeletal muscle is anabolically unresponsive to an amino acid infusion in pediatric burn patients 6 months postinjury. Ann Surg 253:592-7
Durham, William J; Casperson, Shanon L; Dillon, Edgar L et al. (2010) Age-related anabolic resistance after endurance-type exercise in healthy humans. FASEB J 24:4117-27
Dillon, Edgar L; Sheffield-Moore, Melinda; Paddon-Jones, Douglas et al. (2009) Amino acid supplementation increases lean body mass, basal muscle protein synthesis, and insulin-like growth factor-I expression in older women. J Clin Endocrinol Metab 94:1630-7
Dillon, E L; Volpi, Elena; Wolfe, Robert R et al. (2007) Amino acid metabolism and inflammatory burden in ovarian cancer patients undergoing intense oncological therapy. Clin Nutr 26:736-43
Sheffield-Moore, M; Paddon-Jones, D; Sanford, A P et al. (2005) Mixed muscle and hepatic derived plasma protein metabolism is differentially regulated in older and younger men following resistance exercise. Am J Physiol Endocrinol Metab 288:E922-9
Sheffield-Moore, M; Yeckel, C W; Volpi, E et al. (2004) Postexercise protein metabolism in older and younger men following moderate-intensity aerobic exercise. Am J Physiol Endocrinol Metab 287:E513-22
Sheffield-Moore, Melinda; Urban, Randall J (2004) An overview of the endocrinology of skeletal muscle. Trends Endocrinol Metab 15:110-5