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1 Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, MO, USA
2 Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, MO, USA; Department of Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, MO, USA; Dalton Cardiovascular Institute, University of Missouri-Columbia, Columbia, MO, USA
* To whom correspondence should be addressed. E-mail: leessj{at}missouri.edu.
Muscle precursor cells (MPCs) are required for regrowth/regeneration/hypertrophy of skeletal muscle, which are known to be lacking in sarcopenia. The present investigation addressed the issue of age-associated changes in MPC differentiation. MPCs, including satellite cells, were isolated from both young and old rat skeletal muscle with high degree of myogenic purity (>90% MyoD and desmin positive). MPCs isolated from 32 month old (32-mo) rat skeletal muscles exhibited decreased differentiation into myotubes and have decreased myosin heavy chain (MyHC) and muscle creatine kinase (CK-M) expression, compared to MPCs isolated from 3 month old rats (3-mo). p27Kip1 is a cyclin dependent kinase inhibitor that has been shown to enhance muscle differentiation in culture. Here we have shown that p27Kip1 protein was lower in differentiating MPCs from 32-mo skeletal muscle compared to 3-mo skeletal muscle. Although MyHC and CK-M expression were ~50% lower in differentiating MPCs isolated from 32-mo animals, MyoD protein was not different and myogenin protein was 2-fold higher. These data suggest that there are inherent differences in cell signaling during the transition from cell-cycle arrest to the formation of myotubes in MPCs isolated from sarcopenic muscle. Further, there is an age-associated decrease in muscle specific protein expression in differentiating MPCs, despite normal MyoD and elevated myogenin levels.
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