EXCEED THE SPACE PROVIDED. 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. PERFORMANCE SITE ========================================Section End===========================================

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG021566-04
Application #
6930976
Study Section
Special Emphasis Panel (ZRG1-SMB (01))
Program Officer
Kohanski, Ronald A
Project Start
2002-09-30
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
4
Fiscal Year
2005
Total Cost
$379,000
Indirect Cost
Name
University of Washington
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Phelps, Michael; Stuelsatz, Pascal; Yablonka-Reuveni, Zipora (2016) Expression profile and overexpression outcome indicate a role for ?Klotho in skeletal muscle fibro/adipogenesis. FEBS J 283:1653-68
Stuelsatz, Pascal; Shearer, Andrew; Li, Yunfei et al. (2015) Extraocular muscle satellite cells are high performance myo-engines retaining efficient regenerative capacity in dystrophin deficiency. Dev Biol 397:31-44
Carvajal Monroy, Paola L; Yablonka-Reuveni, Zipora; Grefte, Sander et al. (2015) Isolation and Characterization of Satellite Cells from Rat Head Branchiomeric Muscles. J Vis Exp :e52802
Stuelsatz, Pascal; Shearer, Andrew; Yablonka-Reuveni, Zipora (2014) Ancestral Myf5 gene activity in periocular connective tissue identifies a subset of fibro/adipogenic progenitors but does not connote a myogenic origin. Dev Biol 385:366-79
Yoshida, Tadashi; Galvez, Sarah; Tiwari, Sumit et al. (2013) Angiotensin II inhibits satellite cell proliferation and prevents skeletal muscle regeneration. J Biol Chem 288:23823-32
Keire, Paul; Shearer, Andrew; Shefer, Gabi et al. (2013) Isolation and culture of skeletal muscle myofibers as a means to analyze satellite cells. Methods Mol Biol 946:431-68
Shefer, Gabi; Rauner, Gat; Stuelsatz, Pascal et al. (2013) Moderate-intensity treadmill running promotes expansion of the satellite cell pool in young and old mice. FEBS J 280:4063-73
Phelps, Michael; Pettan-Brewer, Christina; Ladiges, Warren et al. (2013) Decline in muscle strength and running endurance in klotho deficient C57BL/6 mice. Biogerontology 14:729-39
Danoviz, Maria Elena; Yablonka-Reuveni, Zipora (2012) Skeletal muscle satellite cells: background and methods for isolation and analysis in a primary culture system. Methods Mol Biol 798:21-52
Stuelsatz, Pascal; Keire, Paul; Almuly, Ricardo et al. (2012) A contemporary atlas of the mouse diaphragm: myogenicity, vascularity, and the Pax3 connection. J Histochem Cytochem 60:638-57

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