Skeletal muscle ability to adapt to intra- and extracellular changes diminishes during ageing and disease; this can lead to muscle wasting. The molecular mechanisms underlying muscle wasting are not fully understood, however redox and epigenetic factors play key regulatory roles in regulating muscle adaptation and its loss.
MicroRNAs control muscle homeostasis through posttranscriptional gene expression regulation. MicroRNAs regulate redox responses in skeletal muscle and equally, redox imbalance can result in changes in microRNA function. Specifically, during conditions characterised by increased ROS, oxidised microRNAs are detected in muscle and serum. Oxidative modification of microRNAs can result in the regulation of non-native targets leading to their disrupted specificity for regulating protein content within muscle and muscle wasting. Our data demonstrate that oxidation of specific microRNAs, which play a role in maintaining muscle homeostasis, such as miR-378 or miR-133, can promote muscle wasting through affecting mitochondrial dynamics, as well as hypertrophy/atrophy pathways. Moreover, our data show that inhibiting oxidised miR-378 positively affects muscle strength. Together, these data indicate a pathological role of oxidised microRNAs in muscle wasting and reveal oxidised microRNAs as potential therapeutic targets.