Tulathromycin B further downstream, a range of genes of importance for oxidative phosphorylation and glycolysis are known to be coordinately suppressed in a variety of models for muscle wasting in rodents and recently also in young human individuals following short term immobilization. Over expression of two of the master genes of mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma co-activator 1 alpha and the close homolog PGC-1b, has been shown to prevent muscle atrophy by inhibiting muscle proteolysis, and the expression levels of PGC-1a and PGC-1b were therefore assessed to investigate the potential age-specificity of this signaling pathway in human disuse muscle atrophy. Although, the importance of apoptosis in human skeletal muscle atrophy has been regarded as controversial, we investigated the importance of this pathway by assessing the expression levels of the Bcl-2�Cassociated X protein, Bcl-2-like protein 1 and tumor protein 53, as apoptosis seems to play an important role in the development of muscle atrophy in aged animal models. Furthermore, the mRNA expression level of Nuclear Factor of kappa light polypeptide gene enhancer in B-cells 1 along with the upstream pro-inflammatory cytokine Tumor Necrosis Factor a were profiled to study the effect of immobility-induced disuse on the induction of the NFkB pathway. In addition, expression levels of the proinflammatory cytokine IL-6 was profiled as an elevated expression of this cytokine along with an increased expression level of TNF-a has been linked to various diseases as well as aging. Collectively, these transcriptional data were combined with measures of contractile capacity, morphology of the Benzethonium Chloride immobilized muscle and protein quantification in order to gain a more thorough understanding of the pathways regulating muscle protein degradation with disuse in old versus young human adults and further to examine the influence of these molecular regulatory pathways on muscle function and muscle size. The mechanisms underlying human skeletal muscle atrophy in aged muscle are largely unknown. In the present study, we report transcriptional data from regulatory signaling pathways related to skeletal muscle disuse-atrophy, which has not previously been studied in aging human muscle. The main findings were that irrespectively of age the ubiquitin-proteasome pathway was activated in the very initial phase of human disusemuscle atrophy along with a marked reduction in markers of oxidative metabolism. Moreover, an age-specific regulation of Akt and S6 phosphorylation was observed with a decrease in young muscle within the first days of immobilization. In contrast, aged muscle demonstrated a rise in Akt phosphorylation at 4 days along with a decrease in mRNA expression levels of MuRF-1 and Atrogin-1 after 14 days of leg muscle immobilization. Furthermore, elderly individuals demonstrated less overall muscle loss with disuse than their young counterparts after 14 days of muscle disuse. Neither the immediate loss in muscle mass, 
nor the subsequent age-differentiated signaling responses could be explained by changes in inflammatory mediators or markers of apoptosis. Certain controversy exists in the literature regarding whether muscle atrophy in human skeletal muscle is regulated primarily via an increase in protein degradation or a decrease in protein synthesis. In animal models, evidence has pointed at protein degradation as the main driving factor, with the ubiquitindependent proteolytic system being rapidly activated.