Daniel Colin Turner

• Sharples, Adam & Turner, Daniel (2023). Skeletal Muscle Memory. American Journal of Physiology - Cell Physiology. ISSN 0363-6143. 324(6), p. c1274–c1294. doi: 10.1152/ajpcell.00099.2023. Full text in Research Archive Show summary

  Skeletal muscle memory is an exciting phenomenon gaining significant traction across several scientific communities, amongst exercise practitioners and the public. Research has demonstrated that skeletal muscle tissue can be 'primed' by earlier positive encounters with exercise training that can enhance adaptation to later training, even following significant periods of exercise cessation or detraining. This review will describe and discuss the most recent research investigating the underlying mechanisms of skeletal muscle memory: 1) 'cellular' muscle memory and, 2) 'epigenetic' muscle memory as well as the emerging evidence of how these theories may work in synergy. We will discuss both 'positive' and 'negative' muscle memory and highlight the importance of investigating muscle memory for optimising exercise interventions and training programmes as well as the development of therapeutic strategies for counteracting muscle wasting conditions and age-related muscle loss. Finally, important directions emerging in the field will be highlighted to advance the next generation of studies in skeletal muscle memory research into the future.

• Gorski, Piotr Patryk; Turner, Daniel; Iraki, Juma; Morton, James P; Sharples, Adam & Areta, José (2023). Human skeletal muscle methylome after low-carbohydrate energy-balanced exercise. American Journal of Physiology. Endocrinology and Metabolism. ISSN 0193-1849. 324(5), p. E437–E448. doi: 10.1152/ajpendo.00029.2023. Show summary

  We aimed to investigate the human skeletal muscle (SkM) DNA methylome after exercise in low carbohydrate (CHO) energy balance (with high fat) compared with exercise in low-CHO energy deficit (with low fat) conditions. The objective to identify novel epigenetically regulated genes and pathways associated with ‘train-low sleep-low’ paradigms. The sleep-low conditions included 9 males that cycled to deplete muscle glycogen while reaching a set energy expenditure. Post-exercise, low-CHO meals (protein-matched) completely replaced (using high-fat) or only partially replaced (low-fat) the energy expended. The following morning resting baseline biopsies were taken and the participants then undertook 75 minutes of cycling exercise, with skeletal muscle biopsies collected 30 minutes and 3.5 hours post exercise. Discovery of genome-wide DNA methylation was undertaken using Illumina EPIC arrays and targeted gene expression analysis was conducted by RT-qPCR. At baseline participants under energy balance (high fat) demonstrated a predominantly hypermethylated (60%) profile across the genome compared to energy deficit-low fat conditions. However, post exercise performed in energy balance (with high fat) elicited a more prominent hypomethylation signature 30 minutes post-exercise in gene regulatory regions important for transcription (CpG islands within promoter regions) compared with exercise in energy deficit (with low fat) conditions. Such hypomethylation was enriched within pathways related to: IL6-JAK-STAT signalling, metabolic processes, p53 / cell cycle and oxidative / fatty acid metabolism. Hypomethylation within the promoter regions of genes: HDAC2, MECR, IGF2 and c13orf16 were associated with significant increases in gene expression in the post-exercise period in energy balance compared with energy deficit. Furthermore, histone deacetylase, HDAC11 was oppositely regulated at the gene expression level compared with HDAC2, where HDAC11 was hypomethylated yet increased in energy deficit compared with energy balance conditions. Overall, we identify some novel epigenetically regulated genes associated with train-low sleep-low paradigms.

• Lautaoja, Juulia H; Turner, Daniel; Sharples, Adam; Kivelä, Riikka; Pekkal, Satu & Hulmi, Juha J [Show all 7 contributors for this article] (2023). Mimicking exercise in vitro - effects of myotube contractions and mechanical stretch on omics. American Journal of Physiology - Cell Physiology. ISSN 0363-6143. 324(4). doi: 10.1152/ajpcell.00586.2022. Full text in Research Archive Show summary

  The number of studies using skeletal muscle (SkM) cell culture models to study exercise in vitro are rapidly expanding. Progressively, more comprehensive analysis methods, such as different omics approaches including transcriptomics, proteomics and metabolomics have been used to examine the intra- and extracellular molecular responses to exercise mimicking stimuli in cultured myotubes. Among other techniques, exercise-like electrical pulse stimulation (EL-EPS) and mechanical stretch of SkM cells are the two most commonly used methods to mimic exercise in vitro. In this mini-review we focus on these two approaches and their effects on the omics of myotubes and/or cell culture media. Furthermore, besides traditional two-dimensional (2D) methods, the use of three-dimensional (3D) SkM approaches are increasing in the field of in vitro exercise mimicry. Our aim with this mini-review is to provide the reader with an up-to-date overview of the 2D and 3D models and the use of omics approaches to study the molecular response to exercise in vitro.

• Gorski, Piotr Patryk; Raastad, Truls; Ullrich, Max; Turner, Daniel; Hallén, Jostein & Sarvari, Sebastian [Show all 8 contributors for this article] (2022). Aerobic Exercise Training Resets the Human Skeletal Muscle Methylome Ten Years after Breast Cancer Treatment and Survival. The FASEB Journal. ISSN 0892-6638. 37(1). doi: 10.1096/fj.202201510RR. Show summary

  Background: Cancer survivors suffer impairments in skeletal muscle in terms of reduced mass and function. Interestingly, human skeletal muscle possesses an epigenetic memory of earlier stimuli, such as exercise. Long-term retention of epigenetic changes in skeletal muscle following cancer survival and/or exercise training have not yet been studied. We therefore investigated genome-wide DNA methylation (methylome) in skeletal muscle following a 5-month, 3/week aerobic-training intervention in breast cancer survivors 10-14 years after diagnosis and treatment. These results were compared to breast cancer survivors who remained untrained and to age-matched controls with no history of cancer, who undertook the same training intervention. Methods: Skeletal muscle biopsies were obtained from 23 females before(pre) and after(post) the 5-month training period. InfiniumEPIC 850K DNA methylation arrays and RT-PCR for gene expression performed. Results: The breast cancer survivors displayed a significant retention of increased DNA methylation (i.e.,hypermethylation) at a larger number of differentially methylated positions (DMPs) compared with healthy age-matched controls pre-training. Training in cancer survivors led to an exaggerated number of DMPs with a hypermethylated signature occurring at non-regulatory regions compared with training in healthy age-matched controls. However, the opposite occurred in important gene regulatory regions, where training in cancer survivors elicited a considerable reduction in methylation (i.e.,hypomethylation) in 99% of the DMPs located in CpG islands within promoter regions. Importantly, training was able to reverse the hypermethylation identified in cancer survivors back towards a hypomethylated signature that was observed pre-training in healthy age-matched controls at 300 (out of 881) of these island/promoter associated CpGs. Pathway enrichment analysis identified training in cancer survivors evoked this predominantly hypomethylated signature in pathways associated with: Cell cycle, DNA replication/repair, transcription, translation, mTOR signalling and the proteosome. Differentially methylated region (DMR) analysis also identified genes: BAG1, BTG2, CHP1, KIFC1, MKL2, MTR, PEX11B, POLD2, S100A6, SNORD104 and SPG7 as hypermethylated in breast cancer survivors, with training reversing these CpG island/promoter associated DMRs towards a hypomethylated signature. Training also elicited a largely different epigenetic response in healthy individuals than that observed in cancer survivors, with very few overlapping changes. Only one gene, SIRT2, was identified as having altered methylation in cancer survivors at baseline and after training in both the cancer survivors and healthy controls. Conclusions: Human skeletal muscle muscle may retain a hypermethylated signature as long as 10-14 years after breast cancer treatment/survival. Five months of aerobic training reset the skeletal muscle methylome towards signatures identified in healthy age-matched individuals in gene regulatory regions.

• Hughes, David C.; Turner, Daniel; Baehr, Leslie M; Seaborne, Robert A.; Viggars, Mark & Jarvis, Jonathan C. [Show all 11 contributors for this article] (2021). Knockdown of the E3 Ubiquitin ligase UBR5 and its role in skeletal muscle anabolism. American Journal of Physiology - Cell Physiology. ISSN 0363-6143. 320(1), p. C45–C56. doi: 10.1152/AJPCELL.00432.2020. Full text in Research Archive

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• Turner, Daniel; Seaborne, Robert A. & Sharples, Adam (2022). Epigenetics of exercise. In Sharples, Adam; Morton, James P & Wackerhage, Henning (Ed.), Molecular Exercise Physiology: An Introduction (Second Edition) . Routledge. ISSN 9781315110752. p. 122–151. doi: 10.4324/9781315110752-6. Show summary

  Epigenetics, meaning ‘above’ genetics, is the topic surrounding the interaction between environmental ‘stressors’, such as exercise, and the modifications it causes to our inherited DNA that may influence the acute molecular response and overall adaptation to exercise. In this chapter, we explain what epigenetics is, and how it is relevant to molecular exercise physiology. We describe and explain the various epigenetic modifications that can occur to our DNA, and how these changes can lead to genes being turned on or off in response to exercise stimuli. We also provide an overview of the most important research looking at changes in these epigenetic modifications after both endurance and resistance exercise. Finally, because epigenetic modifications can be retained (or imprinted’) into our DNA, we discuss the phenomena of ‘muscle memory’ and the research demonstrating that epigenetics plays an important role in skeletal muscle remembering if it has exercised in the past, and how muscle memory might affect adaption to exercise in the future.

• Sharples, Adam; Turner, Daniel; Roth, Stephen; Seaborne, Robert A.; Egan, Brendan & Viggars, Mark [Show all 11 contributors for this article] (2022). Methods in molecular exercise physiology. In Sharples, Adam; Morton, James P & Wackerhage, Henning (Ed.), Molecular Exercise Physiology: An Introduction (Second Edition) . Routledge. ISSN 9781315110752. p. 19–60. doi: 10.4324/9781315110752-2. Show summary

  In this chapter, we describe and explain some of the most important methodology that molecular exercise physiologists use, at level of the molecule and cell, to investigate the microscopic make-up of our cell’s response to exercise. We discuss the important role of blood and muscle biopsy sampling and describe and explain, in detail, the different types of analysis that might be undertaken by molecular exercise physiologists at the molecular (DNA, RNA, protein), cellular and tissue levels. From a muscle tissue biopsy, we describe the process of isolating DNA, RNA, protein and processing of tissue/cells for immunolabelling analysis, as well as primary muscle-derived cell isolation for growing muscle cells in a dish (in-vitro culture). We describe and explain the methods used to analyse a person’s inherited genetic code and sequence variation of DNA between individuals at both the single/targeted gene level and across the genome (genomics), and how to investigate epigenetic modifications to DNA and chromatin again, at both the individual gene level and across the genome (epigenomics). We describe and explain the methods for determining whether our genes are turned on or off in response to exercise at the single gene level and across the ‘transcriptome’ (transcriptomics). We describe and explain the methods for analyses of protein, to measure the abundance and activity of proteins and their role in ‘signal transduction’ in response to exercise at the individual protein level and across the ‘proteome’ (proteomics). We also include a description of the most important immunolabelling methods assessing changes at the protein level in skeletal muscle cell/tissue level that may help confirm the changes (or cellular location of those changes) observed at the molecular level. Finally, we will provide a narrative for the technique of primary muscle cell isolation from human biopsies, and how these isolated cells can be used as ‘in a dish’ (in-vitro) culture models to mimic exercise (in both monolayer and three-dimensional cultures) to compliment molecular analyses from whole-body (in-vivo) human exercise research.

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