Capacity for recovery and possible mechanisms in immobilization atrophy of young and old animals.

The effect of limb immobilization on muscle wasting and recovery of young and old rats was studied. Limb immobilization caused rapid and pronounced muscle weight loss, which was overcome efficiently in the muscles of young animals. However, muscles of old animals did not recover as well, indicating that muscle turnover (degradation and synthesis of proteins) is slower in old muscles than in young ones. The mechanisms of muscle wasting due to immobilization may involve two stages, the fast phase employing calcium-dependent proteolysis and the slower phase recruiting the lysosomal and ubiquitin-proteosome systems. The slow phase most probably involves the penetration of white cells between the muscle fibers and involves the secretion of cytokines that mediate a cascade of intracellular events, which culminates in muscle protein degradation. Thus, it was shown in our study and in other similar reports that through the influence of TNF-alpha and an increase in oxidative stress, there is marked activation of transcription factor NF-kappaB, which in turn induces many proteins to carry the signals that eventually result in protein breakdown. Because protein turnover was shown to slow down with age, it will be of great interest to study these events in aging muscles and to try to ascertain the specific events that make protein breakdown in aged muscles different from that in young ones.