MOLECULAR EVENTS UNDERLYING SKELETAL-MUSCLE ATROPHY AND THE DEVELOPMENT OF EFFECTIVE COUNTERMEASURES

Skeletal muscle adapts to loading; atrophying when exposed to unloadin g on Earth or in spaceflight. Significant atrophy (decreases in muscle fiber cross-section of 11-24%) in humans has been noted after only 5 days in space. Since muscle strength is determined both by muscle cros s-section and synchronization of motor unit recruitment, a loss in mus cle size weakens astronauts, which would increase risks to their safet y if an emergency required maximal muscle force. Numerous countermeasu res have been tested to prevent atrophy. Resistant exercise together w ith growth hormone and IGF-I are effective countermeasures to unloadin g as most atrophy is prevented in animal models. The loss of muscle pr otein is due to an early decrease in protein synthesis rate and a late r increase in protein degradation. The initial decrease in protein syn thesis is a result of decreased protein translation, caused by a prolo ngation in the elongation rate. A decrease in HSP70 by a sight increas e in ATP may be the factors prolonging elongation rate. Increases in t he activities of proteolytic enzymes and in ubiquitin contribute to th e increased protein degradation rate in unloaded muscle. Numerous mRNA concentrations have been shown to be altered in unloaded muscles. Dec reases in mRNAs for contractile proteins usually occur after the initi al fall in protein synthesis rates. Much additional research is needed to determine the mechanism by which muscle senses the absence of grav ity with an adaptive atrophy. The development of effective countermeas ures to unloading atrophy will require more research.