A common clinical problem is that in many nursing homes there are mobile and functioning aged individuals who, upon being subjected to one or more periods of immobility due to illness or injury, are unable to return back to mobility. Even with extensive rehabilitative therapy, many of these individuals are unable to recover to preinjury functioning levels. An animal model mimics this human condition. Both young and old rats who undergo a 10-day period of hindlimb immobilization exhibit disuse atrophy, but only skeletal muscle from young rats successfully regrows from this disuse atrophy as old muscle had no regrowth after 77 days of recovery. Hypothesis 2 reads: """"""""Ten of the 200 mRNAs corresponding to growth factors, growth factor receptors, or post-receptor signaling that are present on the employed microarray will differ between young and old rats during the failure of old skeletal muscle to rescue itself from immobilization-induced atrophy during reloading.
Specific aim 1 will identify a pool of mRNAs associated with the failure of old skeletal muscle to rescue itself from immobilization-induced atrophy during reloading. Another observation is that short-term IGF-I application will rescue the failure of old muscle to regrow after disuse atrophy. However, this effect is only transient as continued IGF-I application to old muscle depletes remaining satellite cell proliferations and muscle wastes. Thus, all defective growth factor responses must be identified.
Specific aim 2 will apply IGF-I to old muscle after hindlimb immobilization in order to further identify those genes that failed to respond in old muscles, but had responded in young muscles.
Specific aim 3 will begin to characterize for those differentially expressed ESTs between young and old muscles after ending immobilization in Specific aims 1 and 2. To support data analysis in Specific aims 1 and 2, Specific aim 4 will develop a computer-based, automated system for analysis of microarray data, data warehousing system for high capacity data storage, and tools for querying microarray data across experiments. Identifying the inappropriately expressed mRNAs associated with failed muscle regrowth of old muscles will permit a more scientifically-based growth factor rescue of old atrophied muscle.
| Morris, R Tyler; Spangenburg, Espen E; Booth, Frank W (2004) Responsiveness of cell signaling pathways during the failed 15-day regrowth of aged skeletal muscle. J Appl Physiol 96:398-404 |
| Pattison, J Scott; Folk, Lillian C; Madsen, Richard W et al. (2003) Expression profiling identifies dysregulation of myosin heavy chains IIb and IIx during limb immobilization in the soleus muscles of old rats. J Physiol 553:357-68 |
| Pattison, J Scott; Folk, Lillian C; Madsen, Richard W et al. (2003) Transcriptional profiling identifies extensive downregulation of extracellular matrix gene expression in sarcopenic rat soleus muscle. Physiol Genomics 15:34-43 |
| Pattison, J Scott; Folk, Lillian C; Madsen, Richard W et al. (2003) Selected Contribution: Identification of differentially expressed genes between young and old rat soleus muscle during recovery from immobilization-induced atrophy. J Appl Physiol 95:2171-9 |
