Influence of physical exercise on microRNAs in skeletal muscle regeneration, aging and diseases

Abstract

Skeletal muscle is a dynamic tissue with remarkable plasticity and its growth and regeneration are highly organized, with the activation of specific transcription factors, proliferative pathways and cytokines. The decline of skeletal muscle tissue with age, is one of the most important causes of functional loss of independence in older adults. Maintaining skeletal muscle function throughout the lifespan is a prerequisite for good health and independent living. Physical activity represents one of the most effective preventive agents for muscle decay in aging. Several studies have underlined the importance of microRNAs (miRNAs) in the control of myogenesis and of skeletal muscle regeneration and function. In this review, we reported an overview and recent advances about the role of miRNAs expressed in the skeletal muscle, miRNAs regulation by exercise in skeletal muscle, the consequences of different physical exercise training modalities in the skeletal muscle miRNA profile, their regulation under pathological conditions and the role of miRNAs in age-related muscle wasting. Specific miRNAs appear to be involved in response to different types of exercise and therefore to play an important role in muscle fiber identity and myofiber gene expression in adults and elder population. Understanding the roles and regulation of skeletal muscle miRNAs during muscle regeneration may result in new therapeutic approaches in aging or diseases with impaired muscle function or re-growth.

Keywords: aging; miRNAs; physical activity; regeneration; skeletal muscle.

Figure 1. Schematic representation of the myogenesis process

Quiescent skeletal muscle satellite cell can become activated following stimuli. The skeletal myoblasts, express transcriptions factors Pax7 and Pax3, as well as the myogenic regulatory factors Myf5 and MyoD. Once committed to differentiation, myoblasts arrest cycling and loose expression of Pax7, Pax3 and Myf5. MRF4 is further required for hypertrophy of the new fibers.

Figure 2. miRNAs involved in skeletal muscle regeneration

Schematic representation of the differentiation stages leading from progenitor muscle cells to terminally differentiated fibers. The most relevant regulatory circuits between miRNAs and protein factors are shown.