Abstract

This is a revised proposal for a Mentored Research Scientist Development Award in Aging for Dr. James D. Fluckey. This human research proposal will allow Dr. Fluckey to expand on his previous work in aging and muscle protein synthesis that was done in rats. Drs. William J. Evans and G. Lynis Dohm will serve as Co-Mentors for this project. Generally, there appears to be a decline of muscle mass and protein synthesis with advancing age, but the underlying cellular mechanisms that regulate reductions of protein synthesis are unclear.
The first aim of this proposal will be to examine rates of muscle protein synthesis in younger, middle-aged and older individuals (20-80 years old), in vitro. Our hypothesis is that muscle protein synthesis, as measured in vitro, will be lower in older (60-80 y) versus middle-aged (40-59 y) or younger (20-39 y) individuals (01der The second aim of this proposal will be to better understand the signaling mechanisms associated with protein synthesis, as well as how they may be affected by age. Two major possibilities for age- related changes in protein synthesis may involve the translation machinery pre se, or with capacity to activate the machinery via signaling mechanisms. Our hypothesis is that an age-related alteration of muscle protein synthesis is a result of altered signal transduction. To test these hypotheses, we will examine rates of protein synthesis and translational efficiency in vitro from abdominal muscle strips obtained from patients undergoing laparoscopic surgery. These in vitro studies will be conducted with or without insulin (specific aim 1), a potent anabolic hormone that has been shown to influence muscle protein synthesis in rats during conditions of muscle atrophy, and with or without specific inhibitors of key signal transduction proteins (specific aim 2). Together, these studies will significantly enhance our understanding of the changes in muscle protein metabolism in senescent muscle and the mechanisms associated with these changes. The proposed studies, mentors, co- investigators, and institutional commitment at the University of Arkansas for Medical Sciences provide an outstanding environment for Dr. Fluckey to develop into an independent research scientist in aging.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AG001025-03
Application #
6643371
Study Section
Special Emphasis Panel (ZAG1-DAG-9 (O1))
Program Officer
Rossi, Winifred K
Project Start
2001-09-30
Project End
2006-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
3
Fiscal Year
2003
Total Cost
$125,245
Indirect Cost

  Institution

Name
University of Arkansas for Medical Sciences
Department
Other Health Professions
Type
Schools of Medicine
DUNS #
122452563
City
Little Rock
State
AR
Country
United States
Zip Code
72205

  Publications

Boudreaux, Ramon D; Swift, Joshua M; Gasier, Heath G et al. (2014) Increased resistance during jump exercise does not enhance cortical bone formation. Med Sci Sports Exerc 46:982-9
Gasier, H G; Riechman, S E; Wiggs, M P et al. (2011) Cumulative responses of muscle protein synthesis are augmented with chronic resistance exercise training. Acta Physiol (Oxf) 201:381-9
Gasier, Heath G; Previs, Stephen F; Pohlenz, Camilo et al. (2009) A novel approach for assessing protein synthesis in channel catfish, Ictalurus punctatus. Comp Biochem Physiol B Biochem Mol Biol 154:235-8
Gasier, Heath G; Riechman, Steven E; Wiggs, Michael P et al. (2009) A comparison of 2H2O and phenylalanine flooding dose to investigate muscle protein synthesis with acute exercise in rats. Am J Physiol Endocrinol Metab 297:E252-9
Norrbrand, Lena; Fluckey, James D; Pozzo, Marco et al. (2008) Resistance training using eccentric overload induces early adaptations in skeletal muscle size. Eur J Appl Physiol 102:271-81
Fluckey, James D; Cortright, Ronald N; Tapscott, Edward et al. (2004) Active involvement of PKC for insulin-mediated rates of muscle protein synthesis in Zucker rats. Am J Physiol Endocrinol Metab 286:E753-8