The overall goal of this 5-year project is to quantitate the alterations in human skeletal muscle function that occur with aging. Muscle function (defined by muscle strength, central and peripheral activation, energy metabolism and fatiguability) of the dorsiflexor muscles of approximately 133 healthy male and female humans will be quantitated using isometric contractions. There will be an even distribution of male and female subjects for all studies, and the age ranges for grouping will be """"""""young"""""""": 25-40 yrs, and """"""""elderly"""""""": 65-85 yrs. To control for effects of muscle size, dorsiflexor muscles fat-free cross-sectional area (CSA) will be quantitated using magnetic resonance imaging. To control for the effects of activity level on measures of muscle function, daily physical activity will be estimated in all subjects (by accelerometer and questionnaire), and the young and elderly groups will be matched for activity as well as by sex. The studies planned will investigate skeletal muscle activation, energy metabolism and fatiguability in young and elderly subjects, and determine the responses of these variables to exercise training in the elderly.
The Specific Aims of this project are: 1) to test the hypothesis that muscle activation is reduced in aging (Year 1); 2) to test the hypothesis that muscle oxidative capacity is reduced in aging (Year 2); 3) to examine muscle fatigue in elderly and young subjects (Year 3); and 4) to determine the effects of exercise training on muscle activation, energy metabolism and fatiguability in the elderly (Year 4-5). Muscle activation will be quantitated using a combination of force and standard neurophysiologic measurements. Muscle energy metabolism will be quantitated using 31-phosphorus magnetic resonance spectroscopy. Muscle fatiguability will be investigated using a progressive, intermittent isometric exercise protocol. This sequence of studies will elucidate the multi-system alterations in muscle function that occur in aging skeletal muscle, and will suggest the extent to which therapeutic exercise training may ameliorate some of these alterations.

National Institute of Health (NIH)
National Institute on Aging (NIA)
First Independent Research Support & Transition (FIRST) Awards (R29)
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Special Emphasis Panel (ZRG4-GRM (01))
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Kent-Braun, J A; Ng, A V; Doyle, J W et al. (2002) Human skeletal muscle responses vary with age and gender during fatigue due to incremental isometric exercise. J Appl Physiol 93:1813-23
Kent-Braun, J A; Ng, A V; Young, K (2000) Skeletal muscle contractile and noncontractile components in young and older women and men. J Appl Physiol 88:662-8
Kent-Braun, J A; Ng, A V (2000) Skeletal muscle oxidative capacity in young and older women and men. J Appl Physiol 89:1072-8
Ng, A V; Kent-Braun, J A (1999) Slowed muscle contractile properties are not associated with a decreased EMG/force relationship in older humans. J Gerontol A Biol Sci Med Sci 54:B452-8