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COUNTERMEASURES TO UNLOADING-INDUCED MUSCLE ATROPHY: ROLE OF MECHANICAL AND PHARMACOLOGICAL INTERVENTIONS. K. M. Baldwin and F. Haddad. Dept. of Physiology and Biophysics, University of California, Irvine; Irvine, CA 92697

   Conditions of skeletal muscle unloading, as occurs during prolonged spaceflight missions and ground based analogues, e.g., bed rest, can produce muscle atrophy of the lower limb extensor muscles (quads and gastroc) amounting to ~25-30% or greater, depending on the degree of current countermeasure intervention. These alterations impede both skeletal muscle and organismal functional capacity that could impede mission objectives when the individual experiences any significant loading condition. The goal of this presentation is to strategically address this problem by first dissecting the gene to protein cascade that is responsible for either muscle growth or the maintenance of protein balance during both anabolic and catabolic conditions. This portion of the presentation will be followed by a dissection of the role of 1) mechanical loading involving stimuli of resistance training in different contraction modes; 2) the intervention of intermittent artificial gravity modalities, the collection of which turn on stimuli involving growth factors promoting positive protein balance; and 3) pharmaceutical approaches aimed targeting (interference of) key steps in the protein degradation pathway (myofibril degradation by the action of proteases such as Caspace 3 and calpain-1,2, and inhibition of key genes such as the ubiquitin ligase, atrogin, and the antigrowth gene myostatin); and 4) the possible combinations of the above approaches in producing a "prescription" for ameliorating the atrophy problem.

Portions of the presentation were supported by a grant from the NASA-NSBRI.