Skeletal muscle atrogenes: From rodent models to human pathologies

Skeletal muscle atrophy is a common side effect of most human diseases. Muscle loss is not only detrimental for the quality of life but it also dramatically impairs physiological processes of the organism and decreases the efficiency of medical treatments. While hypothesized for years, the existence of an atrophying programme common to all pathologies is still incompletely solved despite the discovery of several actors and key regulators of muscle atrophy. More than a decade ago, the discovery of a set of genes, whose expression at the mRNA levels were similarly altered in different catabolic situations, opened the way of a new concept: the presence of atrogenes, i.e. atrophy-related genes. Importantly, the atrogenes are referred as such on the basis of their mRNA content in atrophying muscles, the regulation at the protein level being sometimes more complicate to elucidate. It should be noticed that the atrogenes are markers of atrophy and that their implication as active inducers of atrophy is still an open question for most of them. While the atrogene family has grown over the years, it has mostly been incremented based on data coming from rodent models. Whether the rodent atrogenes are valid for humans still remain to be established. An “atrogene” was originally defined as a gene systematically up- or down-regulated in several catabolic situations. Even if recent works often restrict this notion to the up-regulation of a limited number of proteolytic enzymes, it is important to keep in mind the big picture view. In this review, we provide an update of the validated and potential rodent atrogenes and the metabolic pathways they belong, and based on recent work, their relevance in human physio-pathological situations. We also propose a more precise definition of the atrogenes that integrates rapid recovery when catabolic stimuli are stopped or replaced by anabolic ones. •We provide up-dated definition and list of muscle atrophy-related genes.•Numerous atrogenes are reliable markers of skeletal muscle atrophy in rodents.•At least 11 rodent atrogenes are sensitive to both atrophy and recovery phases.•Some rodent atrogenes, e.g. FoxO transcription factors, are not valid in human.•Despite high intrinsic variability, some human atrogenes have been described.