Selective downregulation of ubiquitin conjugation cascade mRNA occurs in the senescent rat soleus muscle

Aging-related alterations of the ubiquitin proteasome pathway (UPP) have been reported in locomotor skeletal muscle. Specifically, declines in proteasome activity have been observed in the soleus of senescent animals compared to the soleus of young controls. However, the influence of aging on the mRNA levels of key components within the ubiquitin conjugation cascade (UCC) remains unknown. We hypothesized that aged soleus muscle would exhibit downregulated expression of select UCC mRNA and decreased levels of ubiquitin-protein conjugates. To test this postulate, we harvested soleus muscles from 6 and 24-26 month old Fisher 344 rats. Aging resulted in a decline in mRNA expression of two key UCC components in soleus muscle; ubiquitin conjugating enzyme E2(14k) (E214k) and muscle ring finger-1 (MuRF1). Surprisingly, no age-related differences existed in the total content of endogenous ubiquitin-protein conjugates in the soleus muscle. Nonetheless, a selective decrease in the level of ubiquitin-protein conjugates (similar to 30 kDa) was detected in the soleus of senescent animals. These results indicate that the soleus muscle displays a differential mRNA response of select UCC components to aging Furthermore, the decline in E2(14k) and MuRFI mRNA levels may contribute to altered substrate degradation by the UCC in the soleus muscle of senescent rats. (c) 2005 Elsevier Inc. All rights reserved.