Muscle adaptation to immobilisation and rehabilitation training in humans

 

Paul L Greenhaff

School of Biomedical Sciences, The Medical School, University of Nottingham NG7 2UH, UK

 

Animal research suggests the ubiquitin proteasome system (UPS), particularly the ubiquitin ligases MAFbx and MuRF1, are instrumental to immobilisation induced muscle atrophy.  However consistent elevation of these two “atrogenes” has not been observed in human studies. This disparity may be related to the greater severity of procedures performed in animal studies and/or to a lack of time-course data examining the temporal expression of muscle atrogenes in tandem with changes in muscle protein breakdown in humans.  Evidence of a change in muscle protein breakdown over the time-course of muscle disuse remains to be demonstrated in humans and is important to elucidating the true significance of the UPS in immobilisation induced atrophy.  The loss of muscle mass during immobilisation in humans is probably largely the result of a decrease in muscle protein synthesis. However, as signalling via the AKT/mTOR pathway appears to be unchanged in human muscle following immobilisation, the mechanism controlling this decline is not readily apparent.  Six weeks of resistance training reversed the loss of quadriceps mass following 2-3 weeks of immobilisation in humans, but moreover, 24 h after the first bout of rehabilitation exercise, elevated mRNA expression levels of both atrogenes returned to basal. In addition, immobilisation induced increases in mRNA levels of the 20S proteasome subunit HC6, returned to basal 1 week from the initiation of exercise. Likewise, a combination of resistance and aerobic exercise maintained fibre cross sectional area and prevented increased expression of MuRF1 protein in soleus muscle following 60-days bed rest. These observations demonstrate that exercise is able to dampen the UPS in human muscle following disuse atrophy, but the significance and time-course of this exercise induced blunting of the UPS during rehabilitation relative to the temporal change in human muscle protein breakdown is unknown.  The major drive to exercise mediated muscle mass restoration following immobilisation is likely to be attributable to an increase in muscle protein synthesis. However, the mechanism by which this is achieved is unclear, particularly given the dissociation between phosphorylation of the AKT/mTOR pathway and change in human muscle protein synthesis recently observed by several groups.

 

Key words: Muscle growth, muscle wasting, exercise, rehabilitation