MicroRNAs in skeletal muscle and their regulation with exercise, ageing, and disease

Skeletal muscle makes up approximately 40% of the total body mass, providing structural support and enabling the body to maintain posture, to control motor movements and to store energy. It therefore plays a vital role in whole body metabolism. Skeletal muscle displays remarkable plasticity and is able to alter its size, structure and function in response to various stimuli; an essential quality for healthy living across the lifespan. Exercise is an important stimulator of extracellular and intracellular stress signals that promote positive adaptations in skeletal muscle. These adaptations are controlled by changes in gene transcription and protein translation, with many of these molecules identified as potential therapeutic targets to pharmacologically improve muscle quality in patient groups too ill to exercise. MicroRNAs (miRNAs) are recently identified regulators of numerous gene networks and pathways and mainly exert their effect by binding to their target messenger RNAs (mRNAs), resulting in mRNA degradation or preventing protein translation. The role of exercise as a regulatory stimulus of skeletal muscle miRNAs is now starting to be investigated. This review highlights our current understanding of the regulation of skeletal muscle miRNAs with exercise and disease as well as how they may control skeletal muscle health.

MicroRNAs in a hypertrophic heart: from foetal life to adulthood

The heart is the first organ to form and undergoes adaptive remodelling with age. Ventricular hypertrophy is one such adaptation, which allows the heart to cope with an increase in cardiac demand. This adaptation is necessary as part of natural growth from foetal life to adulthood. It may also occur in response to resistance in blood flow due to various insults on the heart and vessels that accumulate with age. The heart can only compensate to this increase in workload to a certain extent without losing its functional architecture, ultimately resulting in heart failure. Many genes have been implicated in cardiac hypertrophy, however none have been shown conclusively to be responsible for pathological cardiac hypertrophy. MicroRNAs offer an alternative mechanism for cellular regulation by altering gene expression. Since 1993 when the function of a non-coding DNA sequence was first discovered in the model organism Caenorhabditis elegans, many microRNAs have been implicated in having a central role in numerous physiological and pathological cellular processes. The level of control these antisense oligonucleotides offer can often be exploited to manipulate the expression of target genes. Moreover, altered levels of microRNAs can serve as diagnostic biomarkers, with the prospect of diagnosing a disease process as early as during foetal life. Therefore, it is vital to ascertain and investigate the function of microRNAs that are involved in heart development and subsequent ventricular remodelling. Here we present an overview of the complicated network of microRNAs and their target genes that have previously been implicated in cardiogenesis and hypertrophy. It is interesting to note that microRNAs in both of these growth processes can be of possible remedial value to counter a similar disease pathophysiology.