Responsiveness of cell signaling pathways during the failed 15-day regrowth of aged skeletal muscle

Various cellular signaling pathways, such as phosphatidylinositol 3-kinase, calcineurin, Janus kinase 2/signal transducer and activator of transcription 3 ( STAT3), and mitogen-activated protein kinase ( MAPK) have been suggested to play an important role in skeletal muscle growth. Old muscle, compared with young muscle, lacks the ability to completely regrow its muscle mass after an atrophy-induced stimulus. it is hypothesized that defects and/or delays in the activation of specific cell signaling pathways of aged soleus muscle limit the potential for growth. To test this, 42 male Fischer 344 x Brown Norway rats, 30 mo old, were hindlimb immobilized for 10 days, and their muscle samples were compared with muscle samples analyzed from 3- to 4-mo-old rats in a previous report (Childs TE, Spangenburg EE, Vyas DR, and Booth FW. Am J Physiol Cell Physiol: 285: C391 - C398, 2003). After 10 days, the immobilization was removed and rats were allowed to ambulate for a series of days. Alterations in the activation or deactivation status of specific signaling pathways were determined by comparing the phosphorylation ( phos) and total concentration of specific signaling proteins ( pan) through Western blotting with the 10-day immobilization group. Various cell signals and their respective time groups of the old rats were shown to be significantly different compared with the 10-day immobilization group. For example, peak increases during recovery from the immobilization were observed at 1) the third recovery day for calcineurin B-pan and 2) the sixth recovery day for glycogen synthase kinase-3beta-phos, p70 S6 kinase (p70(S6k)) - phos and - pan, calcineurin A-pan, STAT3-phos and - pan, p44 MAPK- pan, and p42 MAPK- pan. In contrast, Akt- pan, c- Jun NH2-terminal kinase-phos, and p38 MAPK- phos were observed to decrease from 10-day immobilization values to control levels. Also, Akt-phos was unchanged among all groups. In a follow-up experiment in which muscle samples from both the present study and a previous study ( Childs TE, Spangenburg EE, Vyas DR, and Booth FW. Am J Physiol Cell Physiol: 285: C391 - C398, 2003) were reanalyzed together, the recovery-induced increase in p70(S6k)-phos from immobilization-atrophy was significantly attenuated in soleus muscles of the old group.