9. Gene expression vector- New investigator. Normal aging is associated with a loss of muscle mass and strength, and a decrease in functional ability. During periods of forced bed rest, immobilization or non weight-bearing, elderly individuals often fall victim to an even further decline in muscle function, with devastating consequences for the individual's functional ability and overall well-being. As such the objective of this study is to investigate the potential of virus mediated gene transfer of IGF-1 to guard senescent from secondary atrophy caused by disuse or forced inactivity. Specifically, we hypothesize that in both young adult and elderly muscle virus mediated gene transfer the IGF-1 ameliorates the loss of muscle strength and muscle size induced by immobilization, but not the shift in fiber type distribution. In addition, we hypothesize that virus-mediated gene transfer of IGF-1 expedites the recovery in muscle size and strength following immobilization-induced atrophy. For this purpose the left or right hindlimb (randomized) muscles of both young adult (3 months) and elderly mice (21 months) will be infected with a recombinant adeno-associated virus vector for IGF-1.2 months post-injection, both hindlimbs (injected and control) of the animals will be immobilized in a plaster cast for a period of 4 weeks. At day 28 the cast will be removed and metabolic, morphological and functional characteristics of injected and contralateral control muscles will be determined. Measurements will include muscle cross-sectional area, muscle weight, in vitro force generation and fatiguability, fiber cross- sectional area, fiber type composition, and in vitro oxidative and glycolytic enzyme activity. In order to study the effect of IGF-1 on the recovery of muscle function following immobilization the same measurements will be repeated in a cohort of mice, 1 month and 2 months post-immobilization. We anticipate that the ability to locally manipulate muscle adaptation and growth in the elderly population, especially in the face of secondary atrophy, will be of great clinical importance.
