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