Senile muscle atrophy represents one of the major problems associated with aging and is characterized by loss of strength and muscle mass. These changes ultimately restrict mobility and, consequently, the independence of a growing segment of our society. The proposed research will probe cellular and molecular changes occurring in skeletal muscle during aging. These experiments will focus on the in vitro activity of skeletal muscle satellite cells, the cells responsible for muscle hypertrophy and regeneration. Satellite cells are muscle precursor cells that exist in postnatal muscle and have the ability to divide, differentiate and add new nuclei to existing fibers durng hypertrophy. They also have the ability to form entirely new fibers during regeneration. Because of the importance of these cells in muscle hypertrophy, the diminished capacity of satellite cells in old muscle to respond to normal physiological signals could play a major role in the inability of muscle in older individuals to maintain mass. In the proposed experiments, donor rats from three age groups, young, adult and old, will be used to investigate changes in the proliferative activity of satellite cells in response to a somatomedin-like protein, multiplication stimulating activity (MSA). In addition, age-related changes in the interaction of this hormone with satellite cells will be investigated by determining the affinity of MSA receptors on satellite cells for MSA, the number of receptors present per cell and the rate of internalization of the hormone receptor complex. This research program is designed to provide fundamental insights into the cellular and molecular mechanisms of muscle aging with the ultimate goal of contributing toward the alleviation of problems associated with senile muscle atrophy.
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