Sarcopenia is an age associated reduction in skeletal muscle mass that results from losses of muscle fiber size and fiber number. Sarcopenia reduces muscle function and strength and contributes to increases in the risk of falling, lowering the potential for independent conduct of activities of daily living in the aged. It is hypothesized that the effects of sarcopenia may be delayed or largely prevented if existing muscle fibers and muscle fiber precursor cells could be induced to enter pathways for regeneration, repair and /or hypertrophy. While increased protein synthesis and accumulation of proteins are required for these events, protein synthesis and accumulation are attenuated in muscle from older animals relative to muscle in younger animals. Consequently, muscle of aged humans and other vertebrates have a reduced ability to hypertrophy. It is currently not known which step in the processes that lead to an increase in muscle protein content is responsible for this attenuation in hypertrophy in response to overload. This would occur if transcriptions factors, such as muscle regulator factors (MRF) are lower or have reduced activity in these muscle. A likely source of MRF expression is from satellite cells. The overall goal of this proposal is to determine the significant of MRF transcription factors MyoD and myogenin in satellite cells and myonuclei of aged muscle. A passive stretch overload will be added to one wing of adult, middle aged, aged or senescent Japanese quail. The initial aim is to determine if MRF expression occurs only in proliferating satellite cells of if non-proliferating muscle nuclei contribute to an increase in transcription of MRFs in aging skeletal muscle.
The second aim i s to determine if acute muscle fiber hypertrophy can proceed without the proliferation of satellite cells.
The third aim i s to determine if MRF protein levels are lower or MRF repressor transcript levels are higher in hypertrophy-stimulated nuclei of aged vs. adult animals.
The fourth aim i s to examine if a decrease in myogenin will limit the ability of proliferating satellite cells/myoblasts to fuse with other myoblasts and therefore form new fibers.
The final aim i s to test if """"""""preconditioning"""""""" muscle in young animals by increasing the total nuclei (myonuclei + satellite cells) population, will permit these animals, when aged, to have greater growth potential and force production in response to a hypertrophic stimulus and thereby counteracting sarcopenia.
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|Alway, Stephen E (2002) Attenuation of Ca(2+)-activated ATPase and shortening velocity in hypertrophied fast twitch skeletal muscle from aged Japanese quail. Exp Gerontol 37:665-78|
|Alway, Stephen E; Degens, Hans; Lowe, Dawn A et al. (2002) Increased myogenic repressor Id mRNA and protein levels in hindlimb muscles of aged rats. Am J Physiol Regul Integr Comp Physiol 282:R411-22|
|Alway, Stephen E; Degens, Hans; Krishnamurthy, Gururaj et al. (2002) Potential role for Id myogenic repressors in apoptosis and attenuation of hypertrophy in muscles of aged rats. Am J Physiol Cell Physiol 283:C66-76|
|Lowe, Dawn A; Alway, Stephen E (2002) Animal models for inducing muscle hypertrophy: are they relevant for clinical applications in humans? J Orthop Sports Phys Ther 32:36-43|
|Alway, S E; Lowe, D A; Chen, K D (2001) The effects of age and hindlimb supension on the levels of expression of the myogenic regulatory factors MyoD and myogenin in rat fast and slow skeletal muscles. Exp Physiol 86:509-17|
|Chen, K D; Alway, S E (2001) Clenbuterol reduces soleus muscle fatigue during disuse in aged rats. Muscle Nerve 24:211-22|
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