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Review
. 2025 Mar;125(3):611-627.
doi: 10.1007/s00421-025-05704-6. Epub 2025 Jan 8.

The effect of exercise and physical activity on skeletal muscle epigenetics and metabolic adaptations

Affiliations
Review

The effect of exercise and physical activity on skeletal muscle epigenetics and metabolic adaptations

Gregg Mallett. Eur J Appl Physiol. 2025 Mar.

Abstract

Physical activity (PA) and exercise elicit adaptations and physiological responses in skeletal muscle, which are advantageous for preserving health and minimizing chronic illnesses. The complicated atmosphere of the exercise response can be attributed to hereditary and environmental variables. The primary cause of these adaptations and physiological responses is the transcriptional reactions that follow exercise, whether endurance- (ET) or resistance- training (RT). As a result, the essential metabolic and regulatory pathways and myogenic genes associated with skeletal muscle alter in response to acute and chronic exercise. Epigenetics is the study of the relationship between genetics and the environment. Exercise evokes signaling pathways that strongly alter myofiber metabolism and skeletal muscle physiological and contractile properties. Epigenetic modifications have recently come to light as essential regulators of exercise adaptations. Research has shown various epigenetic markers linked to PA and exercise. The most critical epigenetic alterations in gene transcription identified are DNA methylation and histone modifications, which are associated with the transcriptional response of skeletal muscle to exercise and facilitate the modification to exercise. Other changes in the epigenetic markers are starting to emerge as essential processes for gene transcription, including acetylation as a new epigenetic modification, mediated changes by methylation, phosphorylation, and micro-RNA (miRNA). This review briefly introduces PA and exercise and associated benefits, provides a summary of epigenetic modifications, and a fundamental review of skeletal muscle physiology. The objectives of this review are 1) to discuss exercise-induced adaptations related to epigenetics and 2) to examine the interaction between exercise metabolism and epigenetics.

Keywords: Chronic disease; Endurance training; Metabolism; Resistance training; Skeletal muscle epigenetics.

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Conflict of interest statement

Declarations. Conflict of interest: The author reports no confli of interest, financial, or otherwise, is declared.

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