In aged animals, including humans, the number of fibers in skeletal muscles is decreased. The result is a 25 to 40% decrease in the development of maximum force and a significant impairment in work capacity of the total organism. The weakness and decreased work capacity curtails significantly the activities of the aged. Lengthening contractions of skeletal muscle can result in significant injury to fibers. Following contraction-induced injury the integrity of muscle is restored by regeneration or repair of damaged fibers. The long term objective of the proposed research is to determine the mechanism responsible for the decrease in the number of fibers, and consequently the weakness and reduced work capacity, of muscles of the aged. Compared to fibers in young and mature animals, we hypothesize that fibers in aged animals are more susceptible to injury and regenerate less well. Increased injury and decreased regeneration provides a possible mechanism for the decreased number of fibers in the muscles of aged animals. Studies will be conducted on young (4-6 month), mature (12-14 month), and aged (24-26) month, male mice (strain C57BL/6). Extensor digitorum longus (EDL) muscles will be injured by lengthening contractions known to produce overt histological evidence injury to 25% of the fibers and a decrease of 70% in the development of maximum force in the EDL muscles of young mice. The degree of injury and subsequent repair will be evaluated 1 hour to 60 days after the termination of the lengthening contractions. The differences among the test EDL muscle, the contralateral control EDL muscle, and sham-operated control muscles that undergo passive lengthening, will be assessed by light and electron microscopy, and by measurements of contractile properties. Statistical analyses among the data on young, mature, and aged groups of mice will be used to test hypotheses regarding: 1) The magnitude of the injury induced by the lengthening contractions; 2) the capacity of fibers to regenerate following: a. contraction-induced injury and b. whole muscle grafting with nerves intact; 3) the combined effects of injury and regeneration when structural and functional variables have stabilized; and 4) the effects of repeated exposures to injury producing contractions.
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