Diaphragmatic proteasome function is maintained in the ageing Fisher 344 rat

The diaphragm is the most important inspiratory muscle in mammals and is essential for normal ventilation. Therefore, maintenance of diaphragm function is critical to overall health throughout the lifespan. Evidence indicates that the ubiquitin proteasome pathway (UPP) function is diminished in locomotor skeletal muscle of ageing animals, but the function of the UPP in the senescent diaphragm has not yet been studied. Diaphragms were harvested from 6- and 24- to 26-month-old Fisher 344 rats (n = 8 per group), and a comprehensive assessment of key components of the UPP, proteasome activity and ubiquitin-conjugating enzyme activity was performed. Gene expression and diaphragmatic protein levels of several key proteasome components are not altered in the diaphragm by ageing. Furthermore and most importantly, the senescent diaphragm exhibited no age-related changes in the content of endogenous ubiquitin-protein conjugates or 20S proteasome activity. In conclusion, in contrast to locomotor skeletal muscle, proteasome function and ubiquitin-conjugating enzyme activity are preserved during senescence in diaphragm. A more thorough understanding of the divergent molecular mechanisms and pathways regulating the UPP in different skeletal muscles could lead to the enhancement of therapeutic strategies aimed at improving morbidity and mortality outcomes in different clinical populations.