The impact of mRNA turnover and translation on age-related muscle loss

Abstract

The deterioration of skeletal muscle that develops slowly with age, termed sarcopenia, often leads to disability and mortality in the elderly population. As the proportion of elderly citizens continues to increase due to the dramatic rise in life expectancy, there are rising concerns about the healthcare cost and social burden of caring for geriatric patients. Thus, there is a growing need to understand the underlying mechanisms of sarcopenic muscle loss so that more efficacious therapies may be developed. Building evidence suggests that the onset of age-related muscle loss is linked to the age-related changes in gene expression that occur during sarcopenia. In recent work, the posttranscriptional regulation of gene expression by RNA-binding proteins (RBPs) and microRNA (miRNA) involved in the turnover and translation of mRNA were shown as key players believed to be involved in the induction of muscle wasting. Furthermore, posttranscriptional regulation may also be linked to the reduced ability of muscle satellite cells to contribute to muscle mass during ageing, a key contributing factor to sarcopenic progression. Here we highlight how the activation of pathways such as the p38 MAPK and the phosphoinositide 3-kinase (PI3K) pathways alter the ability of RBPs to regulate the expression of their target mRNAs encoding proteins involved in cell cycle (p21 and p16), as well as myogenesis (Pax7, myogenin and MyoD). Further investigation into the role of RBPs and miRNA during sarcopenia may provide new insights into the development and progression of this disorder, which may lead to the development of new treatment options for elderly patients suffering from sarcopenia.