With aging there is a progressive loss of skeletal muscle mass and strength. As the majority of men age, serum testosterone concentrations decrease toward the lower limits of normal. Testosterone increases muscle mass in older men when given continuously, but studies show equivocal gains in strength. The increase in muscle mass occurs either through stimulation of muscle protein synthesis or inhibition of muscle protein breakdown. Testosterone administration for 1 month to older men increases net protein balance primarily by stimulating muscle protein synthesis while continuous testosterone administration (6 months) increases net balance by inhibiting muscle protein breakdown. This proposal will test the hypothesis that muscle fibers in the setting of increased protein synthesis (cycled testosterone) have improved function over fibers in the setting of inhibition of protein breakdown (continuous testosterone). This improved function in the cycling group will result in greater gains in muscle strength with less chance of long term side effects. Weekly testosterone enanthate (TE) or placebo intramuscular injections will be given for 5 months to older men in three groups, (1) monthly on/off intervals, (2) continuously, or (3) placebo.
Specific aims 1 and 2 will assess the overall improvement in muscle protein net balance and compare monthly myofibrillar and mitochondrial protein synthesis determinations with strength, lean body mass, NMR measurement of oxidative capacity, and detailed single muscle fiber function studies. This proposal will determine whether cycling testosterone administration in older men will increase muscle strength by improving muscle fiber function more than continuous administration. This innovative change in testosterone administration would result in greater gains in strength with fewer side effects.
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