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Long-term insulin-like growth factor-I expression in skeletal muscles attenuates the enhanced in vitro proliferation ability of the resident satellite cells in transgenic miceInsulin-like growth factor-I (IGF-I) overexpression for 1-month in mouse skeletal muscle increases satellite cell proliferation potential. However, it is unknown whether this beneficial enhancement by IGF-I expression would persist over a longer-term duration in aged mice. This is an important issue to address if a prolonged course of IGF-I is to be used clinically in muscle-wasting conditions where satellite cells may become limiting. Using the IGF-I transgenic (IGF-I Tg) mouse that selectively expresses the IGF-I transgene in striated muscles, we found that 18-months of continuous IGF-I overexpression led to a loss in the enhanced in vitro proliferative capacity of satellite cells from Tg skeletal muscles. Also 18-month-old IGF-I Tg satellite cells lost the enhanced BrdU incorporation, greater pRb and Akt phosphorylations, and decreased p27(Kip1) levels initially observed in cells from 1-month-old IGF-I Tg mice. The levels of those biochemical markers reverted to similar values seen in the 18-months WT littermates. These findings, therefore, suggest that there is no further beneficial effect on enhancing satellite cell proliferation ability with persistent long-term expression of IGF-I in skeletal muscles of these transgenic mice.
Document ID
Document Type
Reprint (Version printed in journal)
Chakravarthy, M. V.
(University of Texas Medical School 6431 Fannin Street, Houston, TX 77030, United States)
Fiorotto, M. L.
Schwartz, R. J.
Booth, F. W.
Date Acquired
August 21, 2013
Publication Date
September 1, 2001
Publication Information
Publication: Mechanisms of ageing and development
Volume: 122
Issue: 12
ISSN: 0047-6374
Subject Category
Life Sciences (General)
Funding Number(s)
Distribution Limits
Non-NASA Center
NASA Discipline Musculoskeletal
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