A great many research groups investigate the mechanisms and biochemistry of sarcopenia, the characteristic age-related loss of muscle mass and strength. The most compelling evidence points of a loss of stem cell activity in muscle tissue as the dominant cause, but numerous other mechanisms may contribute. Many researchers are more interested in proximate causes, age-related changes in muscle cell biochemistry, than in deeper causes of the condition. In this context, the review here examines the role of one microRNA out of a number of microRNAs that are of interest in the pathogenesis of sarcopenia.

Frailty is largely associated with sarcopenia, aging-related loss of muscle mass and function, characterised by a progressive and degenerative loss of skeletal muscle mass, quality, and strength during aging. Sarcopenia affects 5-13% of 60-70 year olds and up to 50% of people over 80. The role of microRNAs (miRNAs, miRs) as epigenetic modifiers in regulating loss of muscle mass and function has become increasingly recognised. miRs are short, non-coding RNAs which regulate the expression of approximately two thirds of human genes.

In skeletal muscle, miRs have been demonstrated to control multiple biological processes, including development, regeneration, and aging. A number of miRs are involved in the regulation of muscle protein synthesis, that target regulators involved maintaining the balance between muscle atrophy and hypertrophy, and including regeneration of skeletal muscle. Early studies in humans demonstrated differential expression of miRs in skeletal muscle during aging. We and others have demonstrated the role of miRs in aging-associated processes in skeletal muscle, such as satellite cell senescence and inflammation.

Bioinformatic analyses of non-coding RNAs and transcripts in human and rodent muscle during aging have identified miR-181a as a potentially key regulator of muscle mass and function during aging. In skeletal muscle, miR-181a appears to be the predominant miR-181 family member in skeletal muscle affected by aging and has been suggested as biomarker of muscular health. miR-181 has also been demonstrated to be upregulated in muscle during exercise and predicted to regulate transcription factors and co-activators involved in the adaptive response of muscle to exercise. Based on computer simulation models, miR-181a was predicted to regulate muscle atrophy and hypertrophy through its target genes: HOXA11 by inhibiting MYOD, and SIRT1, through regulating FoxO3 signalling. Indeed, we and others confirmed these as miR-181a direct targets.

More recently, miR-181 family of miRs gained more attention due to their regulation of processes associated with mitochondrial dynamics. Mitochondrial dysfunction is one of the hallmarks of aging. During aging, skeletal muscle is characterised by a loss of mitochondrial content and disrupted mitochondrial turnover, particularly in sedentary individuals. A number of studies to date suggest that miR-181a may be a global regulator of mitochondrial dynamics, redox homeostasis, and potentially energy balance of the whole organism.

Link: https://doi.org/10.1016/j.tma.2020.07.001