Impact of Physical Activity and Exercise on the Epigenome in Skeletal Muscle and Effects on Systemic Metabolism Plaza Díaz, Julio Izquierdo, David Torres Martos, Álvaro Aguilera García, Concepción María Ruiz Ojeda, Francisco Javier Epigenetics Exercise Physical activity Skeletal muscle Metabolism Julio Plaza-Diaz and Concepcion M. Aguilera are part of the "UGR Plan Propio de Investigacion 2016" and the "Excellence actions: Unit of Excellence on Exercise and Health (UCEES), University of Granada". Julio Plaza-Diaz is supported by a fellowship to postdoctoral researchers at foreign universities and research centers from the "Fundacion Ramon Areces", Madrid, Spain. Francisco Javier Ruiz-Ojeda is supported by a fellowship from Spanish Government "Agencia Estatal de Investigacion-Juan de la Cierva-Incorporacion" program (IJC2020-042739-I). Alvaro TorresMartos is supported by the Project "Transductores Moleculares del Ejercicio Fisico y la Activacion del Tejido Adiposo Pardo: en Busca de Nuevas Dianas Terapeuticas en la Comunicacion Intercelular" funded by "Consejeria de Economia, Conocimiento, Empresas y Universidad (PY18-4455), Junta de Andalucia", Spain. 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. 2022-02-04T11:41:14Z 2022-02-04T11:41:14Z 2022-01-07 journal article Plaza-Diaz, J... [et al.]. Impact of Physical Activity and Exercise on the Epigenome in Skeletal Muscle and Effects on Systemic Metabolism. Biomedicines 2022, 10, 126. [https://doi.org/10.3390/biomedicines10010126] http://hdl.handle.net/10481/72670 10.3390/biomedicines10010126 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España MDPI