| Skeletal Muscle is a dynamic tissue that plays an integral role in locomotion, respiration and balance through its unique ability to produce force. Skeletal muscle also serves as the major metabolic engine in the human system. As such, it is of critical importance to maintain healthy muscle tissue. Due to the high variability in its roles, skeletal muscle has evolved into a highly dynamic tissue changing both it genotype and phenotype in response to alterations is loading and other environmental conditions. In healthy individuals skeletal muscle mass will atrophy with unloading/disuse and will recover following normal loading through manipulation of the protein synthetic pathways. Likewise through similar mechanisms, in times of increased loading, skeletal muscle will hypertrophy resulting in the capacity for increased force production. The ability to increase muscle mass in response to loading either following atrophy or in response to increased mechanical loading is severely blunted under several conditions, most notably with aging. This is largely due to severe deficits in the activation of protein synthesis pathways in response to loading as well as changes in the growth factor status. Ultimately, the exact mechanism regulating the failed growth of aged muscle is still unknown. The purpose of these studies was to elucidate several key mechanisms that underlay the reduced capacity for skeletal muscle growth in the elderly population. Two separate conditions associated with aging were isolated and tested whether there was a significant effect on the capacity for muscle growth. The first investigated whether circulating estrogen levels played a role in the ability to recover atrophied muscle mass with reloading. The second study examined whether diet-induced obesity attenuated the ability to increased muscle mass in response to functional overload. It was determined that for both models of skeletal muscle growth, both removal of circulating estrogens and the increased adiposity of diet-induce obesity resulted in the failure in the typical growth response concurrent with the failed activation of the protein synthetic pathways, specifically the Akt/mTOR signaling pathway. Taken together, these results shed some light on possible mechanisms for the attenuated growth of skeletal muscle seen with aging. |
