Increasing muscle capillarization to enhance responses to strength training in sarcopenia

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Sarcopenia, or the aging-related loss of muscle mass, affects >15% of individuals over 70 years of age, and the additional loss of muscle mass after this age can reach 15% per decade. The presence of sarcopenia is associated with physical disability, poor quality of life, all-cause mortality, and direct health care costs amounting to $18.5 billion per year. Reducing the prevalence and consequences of sarcopenia would result in substantial improvements in health as well as heath care cost savings; however, there has been no effective treatment for sarcopenia to date and older adults with sarcopenia may have only minimal muscular responses to resistance exercise training (RT) alone. Because sarcopenic adults have low muscle skeletal muscle capillarization and may lack the adequate perfusion needed to maintain anabolic potential, we propose that the ability of RT to promote muscle hypertrophy may, in part, be dependent on increases in capillarization. This pilot study will test the hypothesis that increasing skeletal muscle capillarization with aerobic exercise training (AEX) prior to RT will result in an improved response of muscle fiber size and mass to RT in sarcopenic older adults. This will be tested through two aims. Aim 1: Determine the effects of 3-month aerobic exercise training followed by 3-month resistance training (AEXRT) compared with 3-month resistance training alone (RT) on skeletal muscle morphology (capillarization and fiber size) in sarcopenic older adults. Aim 2: Determine the effects of AEXRT compared with RT alone on skeletal muscle mass and power in sarcopenic older adults. We will study 32 sarcopenic older adults (70+ years of age) randomized to either AEXRT or RT alone (n=16/group) with matching for sex and race. Participants in the AEXRT group will undergo 3 months of AEX training to increase skeletal muscle capillarization, followed by 3 months of RT. Participants in the RT group will undergo 3 months of RT with no preceding intervention to affect capillarization. Before and after the interventions, participants will complete research testing consisting of: a) vastus lateralis muscle biopsies to measure skeletal muscle fiber size and capillarization; b) muscle strength and power testing (Biodex) to determine muscle function; and c) DXA and CT scans to determine muscle mass, volume and quality. We will also measure gait speed, handgrip strength and 6-minute walk distance and assess physical and mobility function using the Modified Physical Performance Test. Repeated measures ANOVA will be used determine the effects of AEXRT compared with RT only. This patient-oriented study would be the first to test a simple and practical vascular intervention (increasing skeletal muscle capillarization) to improve responses to RT in sarcopenic older adults. While these findings could immediately be translated into more optimal exercise programs for older adults, comprehensive phenotyping at the cellular, tissue, regional, whole-body, and functional levels will provide evidence for a larger trial to establish vascular targets for exercise, nutritional, pharmaceutical or complementary therapies to ameliorate sarcopenia.