Myogenic Stem Cell Function in Aging Skeletal Muscle

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DESCRIPTION (provided by applicant): Skeletal muscle mass, strength and regenerative capacity decline with aging. Enhanced proliferation of myogenic precursor cells in aging muscle could improve the efficiency of myofiber repair and lead to a reduction in age-linked muscle atrophy. Thus, the identification of physiological agents capable of enhancing the function of myogenic precursors in the aging muscle is of significant importance. Satellite cells (located on the surface of the myofiber) are well recognized as the myogenic precursors in postnatal muscle. While satellite cells typically function as tissue-specific myogenic stem cells, multipotent stem cells, capable of giving rise to myogenic cells, have been recently isolated from adult muscle. Gaining insight into the origins of myogenic precursors in adult and aging skeletal muscle as well as the types of cells derived from these precursors can further assist in the design of therapies to improve the number and function of myogenic precursors in aging muscle. The aims of this proposal are: 1) To investigate the effect of fibroblast growth factor (FGF2) on the proliferation of satellite cells in aging muscle. 2) To investigate the potential of cells derived from the vasculature of adult and aging rodents to give rise to skeletal myogenic precursors. 3) To examine the capacity of cells derived from the vasculature to participate in myofiber repair in vivo. Mice will be used throughout the investigations. The effect of FGF on the proliferation of satellite cells will be analyzed in cultures of isolated myofibers. The capacity of the vasculature to give rise to skeletal myogenic cells will be examined with vessels from skeletal muscle and non-skeletal muscle origins. The vasculature-derived cells will be characterized in clonal cultures by immunocytochemistry and RT-PCR. The in vivo studies will examine the ability of cells derived from the vasculature to contribute myofiber nuclei and satellite cells in host muscle of dystrophin-deficient mdx nude mice. The proposed investigation will contribute new insight into the status of myogenic precursors in the adult and aging muscle and can prove important for muscle rehabilitation strategies during disease and aging.