Senile muscle atrophy represents one of the major problems associated with aging and is characterized by loss of strength and muscle mass. These changes restrict the mobility and independence of a growing segment of our society. This project will probe the cellular and molecular changes that occur during muscle aging. In particular, the function of skeletal muscle satellite cells will be evaluated. Satellite cells are the myogenic precursor cells that persist in muscle throughout life and function by adding new nuclei to existing muscle fibers during muscle hypertrophy and by regenerating new fibers following injury. Their ability to proliferate and differentiate in response to three important regulatory protein growth factors, or hormones, is being studied. These hormones are the two insulin-like growth factors (somatomedins) and fibroblast growth factor. In vitro techniques have been devised for monitoring the effects of growth factors on the proliferation and differentiation of cultured satellite cells, and these techniques will be employed to study the normal control of satellite cell activity. In addition, age-related changes in the ability of satellite cells to respond to these growth factors and changes in their growth factor receptor characteristics during aging will be examined. 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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Pathobiochemistry Study Section (PBC)
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University of Arizona
Earth Sciences/Resources
United States
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Kumamoto, T; Kleese, W C; Cong, J Y et al. (1992) Localization of the Ca(2+)-dependent proteinases and their inhibitor in normal, fasted, and denervated rat skeletal muscle. Anat Rec 232:60-77
Allen, R E; Rankin, L L; Greene, E A et al. (1991) Desmin is present in proliferating rat muscle satellite cells but not in bovine muscle satellite cells. J Cell Physiol 149:525-35
Greene, E A; Allen, R E (1991) Growth factor regulation of bovine satellite cell growth in vitro. J Anim Sci 69:146-52
Allen, R E; Rankin, L L (1990) Regulation of satellite cells during skeletal muscle growth and development. Proc Soc Exp Biol Med 194:81-6
Johnson, S E; Allen, R E (1990) The effects of bFGF, IGF-I, and TGF-beta on RMo skeletal muscle cell proliferation and differentiation. Exp Cell Res 187:250-4
Allen, R E; Boxhorn, L K (1989) Regulation of skeletal muscle satellite cell proliferation and differentiation by transforming growth factor-beta, insulin-like growth factor I, and fibroblast growth factor. J Cell Physiol 138:311-5
Ito, M; Pierce, P R; Allen, R E et al. (1989) Effect of monoclonal antibodies on the properties of smooth muscle myosin. Biochemistry 28:5567-72
Thompson, S H; Boxhorn, L K; Kong, W Y et al. (1989) Trenbolone alters the responsiveness of skeletal muscle satellite cells to fibroblast growth factor and insulin-like growth factor I. Endocrinology 124:2110-7
Dodson, M V; Allen, R E; Shimizu, N et al. (1987) Interaction of ovine somatomedin and multiplication stimulating activity/rat insulin-like growth factor II with cultured skeletal muscle satellite cells. Acta Endocrinol (Copenh) 116:425-32
Allen, R E; Boxhorn, L K (1987) Inhibition of skeletal muscle satellite cell differentiation by transforming growth factor-beta. J Cell Physiol 133:567-72

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