Age-related skeletal muscle atrophy (i.e., sarcopenia) accelerates beyond the fifth decade and leads to functional limitations and comorbidities that markedly impair quality of life. Resistance training has shown the most promise among treatments to combat sarcopenia as it enhances muscle function, but induces varying degrees of muscle hypertrophy. The overarching aim is to build on current work in older (60-75 yr) vs. young (20-35 yr) women and men by advancing the understanding of resistance training adaptations using a dose-response approach in older adults, ultimately leading to optimal training program design to combat sarcopenia. A novel resistance training model will be explored (versus 3 others) that is predicted to surpass previous attempts to improve key losses of function associated with sarcopenia (strength, power, and fatigue resistance) by maximizing its impact on the root sarcopenia itself (i.e. by increasing muscle mass and integrity). Myofiber hypertrophy requires net muscle protein synthesis and, as demonstrated during the current funding period/advanced fiber expansion is facilitated by nuclear addition. Over the past 4.25 years of support, key cellular/molecular events within skeletal muscle that likely drive these processes have been identified, and several have been shown to respond in an age- and gender-dependent manner to resistance exercise. Four 30-wk resistance training models will be tested in 60-75 yr adults (n=88: 22 per model;11 women, 11 men) after 4 wk of pre-training to determine which model maximizes muscle growth/regeneration. There are three specific aims: 1) to evaluate the gender-specific efficacy of each model based on muscle hypertrophy and performance;2) to assess net muscle protein synthesis and myonuclear addition, along with key cellular/molecular myogenic processes, driving differences in growth among the models in a potentially gender-specific manner;and 3) to translate the findings of aim 1 to clinically important outcomes by determining the degree to which non-traditional training programs improve mobility function. Relevance: As the U.S. population 65+ yr of age expands to 70 million by 2030, sarcopenia will become a large-scale public health issue as the number of older adults suffering functional limitations will reach epidemic proportions in the absence of effective treatments. The proposed research is a critical step toward defining a broadly applicable intervention to maximize gains in muscle mass and function among elderly.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG017896-10
Application #
8039910
Study Section
Skeletal Muscle and Exercise Physiology Study Section (SMEP)
Program Officer
Dutta, Chhanda
Project Start
1999-10-01
Project End
2013-03-31
Budget Start
2011-04-01
Budget End
2013-03-31
Support Year
10
Fiscal Year
2011
Total Cost
$233,312
Indirect Cost
Name
University of Alabama Birmingham
Department
Physiology
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Kelly, Neil A; Hammond, Kelley G; Stec, Michael J et al. (2018) Quantification and characterization of grouped type I myofibers in human aging. Muscle Nerve 57:E52-E59
Roberts, Brandon M; Lavin, Kaleen M; Many, Gina M et al. (2018) Human neuromuscular aging: Sex differences revealed at the myocellular level. Exp Gerontol 106:116-124
Buford, Thomas W; Carter, Christy S; VanDerPol, William J et al. (2018) Composition and richness of the serum microbiome differ by age and link to systemic inflammation. Geroscience 40:257-268
Stec, Michael J; Thalacker-Mercer, Anna; Mayhew, David L et al. (2017) Randomized, four-arm, dose-response clinical trial to optimize resistance exercise training for older adults with age-related muscle atrophy. Exp Gerontol 99:98-109
Stec, Michael J; Kelly, Neil A; Many, Gina M et al. (2016) Ribosome biogenesis may augment resistance training-induced myofiber hypertrophy and is required for myotube growth in vitro. Am J Physiol Endocrinol Metab 310:E652-E661
Hanks, Lynae J; GutiƩrrez, Orlando M; Bamman, Marcas M et al. (2015) Circulating levels of fibroblast growth factor-21 increase with age independently of body composition indices among healthy individuals. J Clin Transl Endocrinol 2:77-82
Corrick, Katie L; Stec, Michael J; Merritt, Edward K et al. (2015) Serum from human burn victims impairs myogenesis and protein synthesis in primary myoblasts. Front Physiol 6:184
Stec, Michael J; Mayhew, David L; Bamman, Marcas M (2015) The effects of age and resistance loading on skeletal muscle ribosome biogenesis. J Appl Physiol (1985) 119:851-7
Hanks, Lynae J; GutiƩrrez, Orlando M; Ashraf, Ambika P et al. (2015) Bone Mineral Content as a Driver of Energy Expenditure in Prepubertal and Early Pubertal Boys. J Pediatr 166:1397-403
Thalacker-Mercer, Anna; Stec, Michael; Cui, Xiangqin et al. (2013) Cluster analysis reveals differential transcript profiles associated with resistance training-induced human skeletal muscle hypertrophy. Physiol Genomics 45:499-507

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