Skeletal muscle atrophy is a common debilitating condition associated with human immobilisation and ageing resulting in a reduced muscle function. In animal models, loss of muscle mass with immobilisation or unloading has been suggested primarily to occur through an accelerated degradation of myofibrillar proteins via the ubiquitin-proteasome pathway, although rapid decreases in protein synthesis also has been shown. Somewhat in contrast, studies in young human individuals have suggested that a decline in protein synthesis rather than accelerated protein breakdown is responsible for the muscle loss observed with disuse. With aging, muscle loss is suggested to be associated with increased inflammation, decreased anabolic signalling, increased apoptosis, impaired myogenic responsiveness as well as decreased mitochondrial function. Moreover, aging has been found to affect signalling pathways that regulate myogenic growth factors and myofibrillar protein turnover in skeletal muscle of rodents. However, very little is known about how immobilisation and skeletal muscle disuse affects ageing muscle. We therefore set to investigate some of the cellular and molecular mechanisms suggested being responsible for the age-related changes in skeletal muscle with disuse and re-growth, including the differential involvement and time course of such signalling pathways. Recent data from our group indicate that, although immobility induces muscle atrophy in both young and old individuals, the loss in muscle mass is more pronounced in young. Yet, the elderly, compared to young individuals, required a prolonged recovery phase in order to return to initial muscle mass levels following short-term immobilisation. An age-specific regulation of the signalling pathways orchestrating the initiation and time-course of human disuse muscle atrophy was therefore hypothesized and a range of genes from signalling pathways previously demonstrated to play a central role in the regulation of skeletal muscle atrophy and hypertrophy in a variety of animal models was profiled. Collectively, our findings indicate that the time-course and regulation of human skeletal muscle atrophy is age-dependent, leading to an attenuated loss in aging skeletal muscle when exposed to longer periods of immobility-induced disuse. Moreover, age-specific differences may exist for the ability of human skeletal muscle to regenerate after immobility-induced muscle atrophy.