Abstract
Exercise and physical activity induces physiological responses in organisms, and adaptations in skeletal muscle, which is beneficial for maintaining health and preventing and/or treating most chronic diseases. These adaptations are mainly instigated by transcriptional responses that ensue in reaction to each individual exercise, either resistance or endurance. Consequently, changes in key metabolic, regulatory, and myogenic genes in skeletal muscle occur as both an early and late response to exercise, and these epigenetic modifications, which are influenced by environmental and genetic factors, trigger those alterations in the transcriptional responses. DNA methylation and histone modifications are the most significant epigenetic changes described in gene transcription, linked to the skeletal muscle transcriptional response to exercise, and mediating the exercise adaptations. Nevertheless, other alterations in the epigenetics markers, such as epitranscriptomics, modifications mediated by miRNAs, and lactylation as a novel epigenetic modification, are emerging as key events for gene transcription. Here, we provide an overview and update of the impact of exercise on epigenetic modifications, including the well-described DNA methylations and histone modifications, and the emerging modifications in the skeletal muscle. In addition, we describe the effects of exercise on epigenetic markers in other metabolic tissues; also, we provide information about how systemic metabolism or its metabolites influence epigenetic modifications in the skeletal muscle.
Highlights
Some epigenetic changes may play a key role in skeletal muscle, a malleable organ that responds to training sessions by inducing the expression of genes involved in structural, metabolic, and functional adaptations leading to transient changes [30,31]
A complex network of molecular mechanisms is activated in skeletal muscle, and the contraction releases active proteins, nucleic acids, and metabolites that may be involved in the inter-organ communication that is likely to mediate many of the effects of exercise
The interaction between these epigenetic modifications and the complexity of physiology is intricate and this should be further researched in order to elucidate all the signal events occurring during exercise in skeletal muscle
Summary
Skeletal muscle is a plastic tissue capable of adapting rapidly in response to changes in metabolic homeostasis induced by exercise. Endurance training activates the AMPK-MAPK-PGC-1α signaling cascades, leading to increased mitochondrial biogenesis [13] and metabolic adaptations such as fast-to-slow muscle fiber transition, as well as angiogenesis. The attention on this field has increased enormously, and the definition of epigenetics has progressed toward changes in transcriptional expression and/or activity without variation in DNA sequence [20] These changes are of vital importance in fundamental biology, regulating such processes as genomic imprinting and X chromosome inactivation, as well as being the most reliable molecular method of human biological age prediction, collectively underlying its importance and association with development, disease, and aging [21,22]. We highlight the effect of exercise on epigenetic changes in other metabolic tissues such as adipose tissue, liver, pancreas, and brain, and we summarize the main effects of metabolism and its metabolites on epigenetic modifications in the skeletal muscle
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