FRET‐Based Sensor Zebrafish Reveal Muscle Cells Do Not Undergo Apoptosis in Starvation or Natural Aging‐Induced Muscle Atrophy

Muscle atrophy occurs during natural aging and under disease conditions. Muscle cell apoptosis is considered one of the main causes of muscle atrophy, while several recent studies argued that muscle cells do not die during muscle atrophy. Here, sensor zebrafish are generated to visualize muscle cell apoptosis and the engulfment of dead muscle cells by macrophages. Using these sensor zebrafish, starvation, and natural aging-induced muscle atrophy models are established. The data showed that the diameters of muscle cells decreased in both models; however, muscle cell apoptosis is not found in the process of muscle atrophy. In starvation-induced muscle atrophy, it also showed that the number of nuclei in muscle cells remained constant, and there is no increase in the number of macrophages in muscle tissues, both of which further confirmed that muscle cells do not die. In both models, transcriptional analysis showed that the apoptosis pathway is down-regulated, and autophagy and protein degradation pathways are up-regulated. All these data indicated that although there is a great reduction of muscle mass during starvation or aging-induced muscle atrophy, muscle cells do not die by apoptosis. These findings provide new insights into muscle atrophy and can benefit the treatments for muscle atrophy-related diseases.