Does skeletal muscle have an ‘epi’‐memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise

Sharples, Adam P.; Stewart, Claire E.; Seaborne, Robert A.

doi:10.1111/acel.12486

Cited by 153 publications

(127 citation statements)

References 186 publications

(223 reference statements)

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“…Of importance, in this study, a retention of DNA methylation of the myogenic regulatory factor, MyoD was evident over 30 population doublings in muscle cells that receive a single acute (24-h) cytokine stress in early life (24). This study, therefore, points to a potentially important epigenetic mechanism that underlies the susceptibility to loss of muscle mass (25). Furthermore, recent studies that investigated 44 musclespecific genes reported that where low methylation occurred, gene enhancer activity increased (26).…”

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confidence: 61%

Transcriptomic and epigenetic regulation of disuse atrophy and the return to activity in skeletal muscle

et al. 2017

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Physical inactivity and disuse are major contributors to age-related muscle loss. Denervation of skeletal muscle has been previously used as a model with which to investigate muscle atrophy following disuse. Although gene regulatory networks that control skeletal muscle atrophy after denervation have been established, the transcriptome in response to the recovery of muscle after disuse and the associated epigenetic mechanisms that may function to modulate gene expression during skeletal muscle atrophy or recovery have yet to be investigated. We report that silencing the tibialis anterior muscle in rats with tetrodotoxin (TTX)-administered to the common peroneal nerve-resulted in reductions in muscle mass of 7, 29, and 51% with corresponding reductions in muscle fiber cross-sectional area of 18, 42, and 69% after 3, 7, and 14 d of TTX, respectively. Of importance, 7 d of recovery, during which rodents resumed habitual physical activity, restored muscle mass from a reduction of 51% after 14 d TTX to a reduction of only 24% compared with sham control. Returning muscle mass to levels observed at 7 d TTX administration (29% reduction). Transcriptome-wide analysis demonstrated that 3714 genes were differentially expressed across all conditions at a significance of P £ 0.001 after disuse-induced atrophy. Of interest, after 7 d of recovery, the expression of genes that were most changed during TTX had returned to that of the sham control. The 20 most differentially expressed genes after microarray analysis were identified across all conditions and were cross-referenced with the most frequently occurring differentially expressed genes between conditions. This gene subset included myogenin (MyoG), Hdac4, Ampd3, Trim63 (MuRF1), and acetylcholine receptor subunit a1 (Chrna1). Transcript expression of these genes and Fboxo32 (MAFbx), because of its previously identified role in disuse atrophy together with Trim63 (MuRF1), were confirmed by real-time quantitative RT-PCR, and DNA methylation of their promoter regions was analyzed by PCR and pyrosequencing. MyoG, Trim63 (MuRF1), Fbxo32 (MAFbx), and Chrna1 demonstrated significantly decreased DNA methylation at key time points after disuseinduced atrophy that corresponded with significantly increased gene expression. Of importance, after TTX cessation and 7 d of recovery, there was a marked increase in the DNA methylation profiles of Trim63 (MuRF1) and Chrna1 back to control levels. This also corresponded with the return of gene expression in the recovery group back to baseline expression observed in sham-operated controls. To our knowledge, this is the first study to demonstrate that skeletal muscle atrophy in response to disuse is accompanied by dynamic epigenetic modifications that are associated with alterations in gene expression, and that these epigenetic modifications and gene expression profiles are reversible after skeletal muscle returns to normal

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confidence: 61%

Transcriptomic and epigenetic regulation of disuse atrophy and the return to activity in skeletal muscle

et al. 2017

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“…As comprehensively reviewed by Adam Sharples and colleagues, there is ample evidence that also SCs can retain a mitotically heritable “epi”‐memory of prior physical activity, metabolic challenges, as well as of prior maladaptive states (Sharples, Stewart, & Seaborne, 2016). SCs are indispensable to promote muscle repair and regeneration, but their actual role(s) in adult skeletal muscle homeostasis and exercise adaptation is not comprehensively understood.…”

Section: Transcriptional Memory Enables Learning From Experiencementioning

confidence: 99%

Transcriptional memory in skeletal muscle. Don't forget (to) exercise

Beiter

Nieß

Moser

2020

Journal Cellular Physiology

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Transcriptional memory describes an ancient and highly conserved form of cellular learning that enables cells to benefit from recent experience by retaining a mitotically inheritable but reversible memory of the initial transcriptional response when encountering an environmental or physiological stimulus. Herein, we will review recent progress made in the understanding of how cells can make use of diverse constituents of the epigenetic toolbox to retain a transcriptional memory of past states and perturbations. Specifically, we will outline how these mechanisms will help to improve our understanding of skeletal muscle plasticity in health and disease. We describe the epigenetic road map that allows skeletal muscle fibers to navigate through training‐induced adaptation processes, and how epigenetic memory marks can preserve an autobiographical history of lifestyle behavior changes, pathological challenges, and aging. We will further consider some key findings in the field of exercise epigenomics to emphasize major challenges when interpreting dynamic changes in the chromatin landscape in response to acute exercise and training.

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“…These environmentally regulated modifications of DNA and histones impact transcriptional control by altering spatial accessibility of DNA and chromatin structure, as well as recruitment of histone-modifying factors. Epigenetic programming is impacted by both acute and chronic exercise and central to skeletal muscle metabolic regulatory control (Howlett and McGee 2016) and maintenance of skeletal muscle mass with aging (Sharples et al 2016). DNA methylation is dramatically altered by exercise training in both human skeletal muscle (Nitert et al 2012) and adipose tissue (Ronn et al 2013).…”

Section: Genome and Epigenomementioning

confidence: 99%

Omics and Exercise: Global Approaches for Mapping Exercise Biological Networks

Hoffman

2017

Cold Spring Harb Perspect Med

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The application of global "-omics" technologies to exercise has introduced new opportunities to map the complexity and interconnectedness of biological networks underlying the tissue-specific responses and systemic health benefits of exercise. This review will introduce major research tracks and recent advancements in this emerging field, as well as critical gaps in understanding the orchestration of molecular exercise dynamics that will benefit from unbiased omics investigations. Furthermore, significant research hurdles that need to be overcome to effectively fill these gaps related to data collection, computation, interpretation, and integration across omics applications will be discussed. Collectively, a cross-disciplinary physiological and omics-based systems approach will lead to discovery of a wealth of novel exercise-regulated targets for future mechanistic validation. This frontier in exercise biology will aid the development of personalized therapeutic strategies to improve athletic performance and human health through precision exercise medicine.T he dynamic human physiological responses to exercise have been widely studied in the context of metabolism and mechanical stress. Health benefits of exercise in prevention, delay, and/or treatment of pathophysiology associated with metabolic disorders and aging are widely appreciated. However, the intricacies of molecular networks and biological mechanisms underlying how humans adapt to exercise and acquire health benefits are not fully understood. In response to perturbations in whole-body homeostasis induced by physical activity and exercise, biological networks are stimulated in various cell types and organs to manage systemic metabolic and mechanical demands (Hawley et al. 2014). Targeted, reductionist-based approaches have laid the foundation for our understanding of distinct biological mechanisms regulating acute versus repeated exercise adaptations using a range of experimental models from cells to animals and humans. However, the complexity and integrated nature of the whole-body exercise response warrants global unbiased systems approaches to unravel the interwoven networks underlying the benefits of exercise in health and disease.In this early stage of the exercise and omics revolution, there is a wealth of molecular information now within reach to help build on our understanding of human metabolism and exercise physiology. There is tremendous potential for omics approaches to fill critical gaps in our

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Does skeletal muscle have an ‘epi’‐memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise

Cited by 153 publications

References 186 publications

Transcriptomic and epigenetic regulation of disuse atrophy and the return to activity in skeletal muscle

Transcriptomic and epigenetic regulation of disuse atrophy and the return to activity in skeletal muscle

Transcriptional memory in skeletal muscle. Don't forget (to) exercise

Omics and Exercise: Global Approaches for Mapping Exercise Biological Networks

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