Adam Philip Sharples

• Jacques, Macsue; Seale, Kirsten; Voisin, Sarah; Lysenko, Anna; Grolaux, Robin & Jones-Freeman, Bernadette [Vis alle 29 forfattere av denne artikkelen] (2026). Meta-analysis of DNA methylation aging signatures in 17 human tissues. Nature Aging. doi: 10.1038/s43587-026-01164-5. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Epigenetic changes, in particular DNA methylation, accumulate with age across different tissues, but whether these changes follow consistent patterns across different organs remains poorly understood. Here we show, through a meta-analysis of more than 15,000 human methylation profiles spanning 17 tissues, that aging produces both conserved and tissue-specific epigenetic signatures. We identify systemic shifts in methylation levels, increases in methylation variability, and growing molecular disorder across tissues. Network analysis revealed tightly connected gene clusters that are not modified by beneficial interventions, alongside a more modifiable cluster linked to NAD + metabolism, supporting NAD + as a potential therapeutic target in aging. A gene encoding a cell-adhesion protein, PCDHGA1, emerged as a conserved hub across tissues, implicating cell-to-cell communication pathways in aging across multiple organs. Our methylation atlas therefore provides a resource for dissecting the molecular basis of human aging and for identifying potential biomarkers and translational therapies.

• Turner, Daniel; Raastad, Truls; Ullrich, Max; Christiansen, Stian; Sutherland, Hazel & Boot, James [Vis alle 15 forfattere av denne artikkelen] (2026). Repeated Disuse Atrophy Imprints a Molecular Memory in Skeletal Muscle: Transcriptional Resilience in Young Adults and Susceptibility in Aged Muscle. Advanced Science. doi: 10.1002/advs.202522726. Fulltekst i vitenarkiv Vis sammendrag

  Disuse-induced muscle atrophy commonly occurs following illness, injury, or falls and becomes increasingly frequent with ageing. Whether skeletal muscle retains a “memory” of repeated disuse remains unknown. We investigated repeated lower-limb immobilization in young adults and a refined aged rat model, integrating physiological, multi-omic, immunohistochemical, biochemical, and primary human muscle stem cell (MuSC) analyses. To enable robust age comparisons, we integrated previously published young rat data with newly generated aged rat data. In young human muscle, repeated disuse elicited attenuated transcriptional perturbations in oxidative and mitochondrial pathways, suggestive of a protective molecular memory, despite similar atrophy to initial disuse. In contrast, aged muscle exhibited a detrimental memory, characterized by greater atrophy, exaggerated suppression of aerobic metabolism genes despite recovery after initial disuse, NAD+ and mitochondrial DNA depletion, and activation of proteasomal, extracellular-matrix, and DNA-damage pathways. Whereas young rats recovered muscle mass after initial disuse, aged rats failed to do so. Across species, repeated disuse induced DNA hypermethylation and downregulation of aerobic metabolism and mitochondrial gene networks. NR4A1 and NR4A3 were among the strongest disuse-suppressed genes; NR4A1 acquired recovery-phase hypermethylation that maintained its transcriptional repression, while NR4A3 was the most downregulated gene after initial atrophy and remained persistently suppressed into recovery. Acetylcholine receptor subunit genes (CHRNA1, CHRND) were epigenetically primed, demonstrating hypomethylation and strong upregulation after disuse, and further amplification after repeated atrophy, while CHRNG was selectively induced after repeated atrophy only. NMRK2, an NAD+ biosynthesis gene, was the most downregulated gene across both atrophy periods, and supplementation with its substrate, nicotinamide riboside (NR), improved myotube size in MuSCs derived post-atrophy. Overall, repeated disuse atrophy imprints a molecular memory in skeletal muscle shaping transcriptional resilience in young adults and exaggerated susceptibility in aged muscle.

• Jacques, Macsue; Landen, Shanie; Sharples, Adam P.; Garnham, Andrew; Schittenhelm, Ralf & Steele, Joel [Vis alle 36 forfattere av denne artikkelen] (2025). Molecular landscape of sex- and modality-specific exercise adaptation in human skeletal muscle through large-scale multi-omics integration. Cell reports. 44(6). doi: 10.1016/j.celrep.2025.115750. Fulltekst i vitenarkiv Vis sammendrag

  We investigated the molecular mechanisms of exercise adaptations in human muscle by integrating genome, methylome, transcriptome, and proteome data from over 1,000 participants (2,340 muscle samples). We identified distinctive signatures associated with maximal oxygen consumption (VO2max), and multi-omics integration uncovered five key genes as robust exercise markers across layers, with transcription factors functioning as activators, synergizing with DNA methylation to regulate gene expression. Minimal sex differences were observed, while modality-specific analysis highlighted distinct pathways for aerobic and resistance exercise, contrasting with muscle disuse patterns. Finally, we created a webtool, OMAx, featuring our individual omics and integration analysis. These findings provide a comprehensive multi-omics framework for understanding exercise-induced molecular adaptations, offering insights into muscle health, cardiorespiratory fitness, and their roles in aging and disease prevention.

• Hulmi, Juha J; Halonen, Eeli J; Sharples, Adam; O'Connell,, Thomas M; Kuikka, Lauri & Lappi, Veli-Matti [Vis alle 10 forfattere av denne artikkelen] (2025). Human skeletal muscle possesses both reversible proteomic signatures and a retained proteomic memory after repeated resistance training. Journal of Physiology. ISSN 0022-3751. 603(9), s. 2655–2673. doi: 10.1113/JP288104. Fulltekst i vitenarkiv Vis sammendrag

  Investigating repeated resistance training (RT) separated by a training break enables exploration of the potential for a proteomic memory of RT-induced skeletal muscle growth, i.e. retained protein adaptations from the previous RT. Our aim was to examine skeletal muscle proteome response to 10-week RT (RT1) followed by 10-week training cessation (i.e. detraining, DT), and finally, 10-week retraining (RT2). Thirty healthy, untrained participants conducted either periodic RT (RT1-DT-RT2, n = 17) or a 10-week no-training control period (n = 13) followed by 20 weeks of RT (n = 11). RT included twice-weekly supervised whole-body RT sessions, and resting vastus lateralis biopsies were obtained every 10 weeks for proteomics analysis using high-end dia-PASEF's mass spectrometry. The first RT period altered 150 proteins (93% increased) involved in, for example, energy metabolism and protein processing compared to minor changes during the control period. The proteome adaptations were similar after the second RT compared to baseline demonstrating reproducibility in proteome adaptations to RT. Many of the proteins induced by RT1 were reversed towards baseline after detraining and increased again after retraining. These reversible proteins were especially involved in aerobic energy metabolism. Interestingly, several proteins which increased after RT1 remain elevated (i.e. retained) after detraining, including carbonyl reductase 1 (CBR1) and proteins involved in muscle contraction, cytoskeleton and calcium binding. Among the latter, calcium-activated protease calpain-2 (CAPN2) has been recently identified as an epigenetic muscle memory gene. We show that resistance training evokes retained protein levels even after 2.5 months of no training, which demonstrates a potential proteomic memory of resistance training-induced muscle growth in human skeletal muscle.

• Jacques, Macsue; Seale, Kirsten; Voisin, Sarah; Lysenko, Anna; Grolaux, Robin & Jones-Freeman, Bernadette [Vis alle 16 forfattere av denne artikkelen] (2025). DNA Methylation Ageing Atlas Across 17 Human Tissues. BioRxiv. ISSN 0362-4331. doi: 10.1101/2025.07.21.665830. Fulltekst i vitenarkiv
• Baehr, Leslie M; Sousa, Luis Gustavo Oliveira de; Goodman, Craig A; Sharples, Adam; Waddell, David S. & Bodine, Sue C. [Vis alle 7 forfattere av denne artikkelen] (2025). Response of UBR-box E3 ubiquitin ligases and protein quality control pathways to perturbations in protein synthesis and skeletal muscle size. American Journal of Physiology - Cell Physiology. 329(6), s. C1706–C1722. doi: 10.1152/ajpcell.00602.2025. Fulltekst i vitenarkiv Vis sammendrag

  The N-degron pathway contributes to proteolysis by targeting N-terminal residues of destabilized proteins via E3 ligases that contain a UBR-box domain. Emerging evidence suggests the UBR-box family of E3 ubiquitin ligases (UBR1-7) are involved in the positive regulation of skeletal muscle mass. The purpose of this study was to explore the role of UBR-box E3 ubiquitin ligases under enhanced protein synthesis and skeletal muscle growth conditions. Cohorts of adult male mice were electroporated with constitutively active Akt (Akt-CA) or UBR5 RNAi constructs with a rapamycin diet intervention for 7 and 30 days, respectively. In addition, the UBR-box family was studied during the regrowth phase post nerve crush induced inactivity. Skeletal muscle growth with Akt-CA or regrowth following inactivity increased protein abundance of UBR1, UBR2, UBR4, UBR5 and UBR7. This occurred with corresponding increases in Akt-mTORC1/S6K and MAPK/p90RSK signaling and protein synthesis. The increases in UBR-box E3s, ubiquitination, and proteasomal activity occurred independently of mTORC1 activity and were associated with increases in markers related to autophagy, ER-stress, and protein quality control pathways. Finally, while UBR5 knockdown (KD) evokes atrophy, it occurs together with hyperactivation of mTORC1 and protein synthesis. In UBR5 KD muscles, we identified an increase in protein abundance for UBR2, UBR4 and UBR7, which may highlight a compensatory response to maintain proteome integrity. Future studies will seek to understand the role of UBR-box E3s towards protein quality control in skeletal muscle plasticity.

• Sharples, Adam (2024). Epigenome-proteome integration in aged skeletal muscle after exercise training. Journal of Physiology. ISSN 0022-3751. 603(1), s. 29–31. doi: 10.1113/JP287235. Fulltekst i vitenarkiv
• Pillotto, Andrea; Turner, Daniel; Mazzolari, Raffaele; Crea, Emanuela; Brocca, Lorenza & Pellegrino, Maria Antonietta [Vis alle 10 forfattere av denne artikkelen] (2024). Human skeletal muscle possesses an epigenetic memory of high-intensity interval training. American Journal of Physiology - Cell Physiology. 328(1), s. C258–C272. doi: 10.1152/ajpcell.00423.2024. Fulltekst i vitenarkiv Vis sammendrag

  Human skeletal muscle displays an epigenetic memory of resistance exercise induced-hypertrophy. It is unknown, however, whether high-intensity interval training (HIIT) also evokes an epigenetic muscle memory. This study used repeated training intervention interspersed with a detraining period to assess epigenetic memory of HIIT. Twenty healthy subjects (25 ± 5 yr) completed two HIIT interventions (training and retraining) lasting 2 mo, separated by 3 mo of detraining. Measurements at baseline, after training, detraining, and retraining included maximal oxygen consumption (V̇o2max). Vastus lateralis biopsies were taken for genome-wide DNA methylation and targeted gene expression analyses. V̇o2max improved during training and retraining (P 0.58). Thousands of differentially methylated positions (DMPs) predominantly demonstrated a hypomethylated state after training, retained even after 3-mo of exercise cessation and into retraining. Five genes, ADAM19, INPP5a, MTHFD1L, CAPN2, and SLC16A3, possessed differentially methylated regions (DMRs) with retained hypomethylated memory profiles and increased gene expression. The retained hypomethylation during detraining was associated with an enhancement in expression of the same genes even after 3 mo of detraining. SLC16A3, INPP5a, and CAPN2 are involved in lactate transport and calcium signaling. Despite similar physiological adaptations between training and retraining, memory profiles were found at epigenetic and gene expression level, characterized by retained hypomethylation and increased gene expression after training into long-term detraining and retraining. These genes were associated with calcium signaling and lactate transport. Although significant memory was not observed in physiological parameters, our novel findings indicate that human skeletal muscle possesses an epigenetic memory of HIIT.

• Sharples, Adam (2024). A multi-epigenomic map of endurance exercise training. Trends in Genetics. ISSN 0168-9525. 40(9), s. 736–738. doi: 10.1016/j.tig.2024.06.005. Fulltekst i vitenarkiv Vis sammendrag

  The Molecular Transducers of Physical Activity Consortium (MoTrPAC) aims to comprehensively map molecular alterations in response to acute exercise and chronic training. In one of a recent series of papers from MoTrPAC, Nair et al. provide the first multi-epigenomic and transcriptomic integration across eight tissues in both sexes following adaptation to endurance exercise training (EET).

• Voisin, Sarah; Seale, Kirsten; Jacques, Macsue; Landen, Shanie; Harvey, Nicholas R & Haupt, Larisa M [Vis alle 27 forfattere av denne artikkelen] (2023). Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle. Aging Cell. ISSN 1474-9718. doi: 10.1111/acel.13859. Fulltekst i vitenarkiv Vis sammendrag

  Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3176). We show that: (1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, (2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns toward a younger profile, and (3) muscle disuse "ages" the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted toward a younger state after exercise training interventions, while the transcriptome shifted toward an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism, and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity.

• Lautaoja, Juulia H; Turner, Daniel; Sharples, Adam; Kivelä, Riikka; Pekkal, Satu & Hulmi, Juha J [Vis alle 7 forfattere av denne artikkelen] (2023). Mimicking exercise in vitro - effects of myotube contractions and mechanical stretch on omics. American Journal of Physiology - Cell Physiology. 324(4). doi: 10.1152/ajpcell.00586.2022. Fulltekst i vitenarkiv Vis sammendrag

  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; 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), s. E437–E448. doi: 10.1152/ajpendo.00029.2023. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Sharples, Adam & Turner, Daniel (2023). Skeletal Muscle Memory. American Journal of Physiology - Cell Physiology. 324(6), s. c1274–c1294. doi: 10.1152/ajpcell.00099.2023. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Sexton, Casey L; Godwin, Joshua S.; Mcintosh, Mason; Ruple, Bradley A; Osburn, Shelby C & Hollingsworth, Blake [Vis alle 18 forfattere av denne artikkelen] (2023). Skeletal Muscle DNA Methylation and mRNA Responses to a Bout of Higher versus Lower Load Resistance Exercise in Previously Trained Men. Cells. 12(2). doi: 10.3390/cells12020263. Fulltekst i vitenarkiv Vis sammendrag

  We sought to determine the skeletal muscle genome-wide DNA methylation and mRNA responses to one bout of lower load (LL) versus higher load (HL) resistance exercise. Trained college-aged males (n = 11, 23 ± 4 years old, 4 ± 3 years self-reported training) performed LL or HL bouts to failure separated by one week. The HL bout (i.e., 80 Fail) consisted of four sets of back squats and four sets of leg extensions to failure using 80% of participants estimated one-repetition maximum (i.e., est. 1-RM). The LL bout (i.e., 30 Fail) implemented the same paradigm with 30% of est. 1-RM. Vastus lateralis muscle biopsies were collected before, 3 h, and 6 h after each bout. Muscle DNA and RNA were batch-isolated and analyzed using the 850k Illumina MethylationEPIC array and Clariom S mRNA microarray, respectively. Performed repetitions were significantly greater during the 30 Fail versus 80 Fail (p < 0.001), although total training volume (sets × reps × load) was not significantly different between bouts (p = 0.571). Regardless of bout, more CpG site methylation changes were observed at 3 h versus 6 h post exercise (239,951 versus 12,419, respectively; p < 0.01), and nuclear global ten-eleven translocation (TET) activity, but not global DNA methyltransferase activity, increased 3 h and 6 h following exercise regardless of bout. The percentage of genes significantly altered at the mRNA level that demonstrated opposite DNA methylation patterns was greater 3 h versus 6 h following exercise (~75% versus ~15%, respectively). Moreover, high percentages of genes that were up- or downregulated 6 h following exercise also demonstrated significantly inversed DNA methylation patterns across one or more CpG sites 3 h following exercise (65% and 82%, respectively). While 30 Fail decreased DNA methylation across various promoter regions versus 80 Fail, transcriptome-wide mRNA and bioinformatics indicated that gene expression signatures were largely similar between bouts. Bioinformatics overlay of DNA methylation and mRNA expression data indicated that genes related to “Focal adhesion,” “MAPK signaling,” and “PI3K-Akt signaling” were significantly affected at the 3 h and 6 h time points, and again this was regardless of bout. In conclusion, extensive molecular profiling suggests that post-exercise alterations in the skeletal muscle DNA methylome and mRNA transcriptome elicited by LL and HL training bouts to failure are largely similar, and this could be related to equal volumes performed between bouts.

• Viggars, Mark; Nolan, Andy; Sharples, Adam & Stewart, Claire (2023). Skeletal Muscle Satellite Cell Physiology and Function: Complimentary In Vitro and In Vivo Models and Methods. I Atherton, P.J. & Wilkinson, Daniel J. (Red.), Neuromuscular Assessments of Form and Function. Humana Press. ISSN 9781071633144. s. 243–274. doi: 10.1007/978-1-0716-3315-1_13. Fulltekst i vitenarkiv
• McIntosh, Mason C; Sexton, Casey L; Godwin, Joshua S.; Ruple, Bradley A; Michel, J. Max & Plotkin, Daniel L. [Vis alle 15 forfattere av denne artikkelen] (2023). Different Resistance Exercise Loading Paradigms Similarly Affect Skeletal Muscle Gene Expression Patterns of Myostatin-Related Targets and mTORC1 Signaling Markers. Cells. 12(6). doi: 10.3390/cells12060898. Fulltekst i vitenarkiv Vis sammendrag

  Although transcriptome profiling has been used in several resistance training studies, the associated analytical approaches seldom provide in-depth information on individual genes linked to skeletal muscle hypertrophy. Therefore, a secondary analysis was performed herein on a muscle transcriptomic dataset we previously published involving trained college-aged men (n = 11) performing two resistance exercise bouts in a randomized and crossover fashion. The lower-load bout (30 Fail) consisted of 8 sets of lower body exercises to volitional fatigue using 30% one-repetition maximum (1 RM) loads, whereas the higher-load bout (80 Fail) consisted of the same exercises using 80% 1 RM loads. Vastus lateralis muscle biopsies were collected prior to (PRE), 3 h, and 6 h after each exercise bout, and 58 genes associated with skeletal muscle hypertrophy were manually interrogated from our prior microarray data. Select targets were further interrogated for associated protein expression and phosphorylation induced-signaling events. Although none of the 58 gene targets demonstrated significant bout x time interactions, ~57% (32 genes) showed a significant main effect of time from PRE to 3 h (15↑ and 17↓, p < 0.01), and ~26% (17 genes) showed a significant main effect of time from PRE to 6 h (8↑ and 9↓, p < 0.01). Notably, genes associated with the myostatin (9 genes) and mammalian target of rapamycin complex 1 (mTORC1) (9 genes) signaling pathways were most represented. Compared to mTORC1 signaling mRNAs, more MSTN signaling-related mRNAs (7 of 9) were altered post-exercise, regardless of the bout, and RHEB was the only mTORC1-associated mRNA that was upregulated following exercise. Phosphorylated (phospho-) p70S6K (Thr389) (p = 0.001; PRE to 3 h) and follistatin protein levels (p = 0.021; PRE to 6 h) increased post-exercise, regardless of the bout, whereas phospho-AKT (Thr389), phospho-mTOR (Ser2448), and myostatin protein levels remained unaltered. These data continue to suggest that performing resistance exercise to volitional fatigue, regardless of load selection, elicits similar transient mRNA and signaling responses in skeletal muscle. Moreover, these data provide further evidence that the transcriptional regulation of myostatin signaling is an involved mechanism in response to resistance exercise.

• Stewart, Claire E & Sharples, Adam (2022). Aging, Skeletal Muscle, and Epigenetics. Plastic and Reconstructive Surgery. ISSN 0032-1052. 150(4S-2), s. 27S–33S. doi: 10.1097/PRS.0000000000009670. Fulltekst i vitenarkiv Vis sammendrag

  We are living in an aging society. In 2019, 1 billion individuals were already aged over 60. The number of people in this demographic is predicted to reach 1.4 billion by 2030 and 2.1 billion by 2050 (WHO). In the USA, individuals over 65 represent the fastest growing segment of the population (US census bureau). Similar trends are seen in the UK, with 16.2 million people already aged over 60, equivalent to 24% of the total population (Age UK; https://www.ageuk.org.uk/globalassets/age-uk/documents/reports-and-publications/later_life_uk_factsheet.pdf). Indeed, in the UK, people over the age of 60 outnumbered those under the age of 18, for the first time in 2008. This statistic still prevails today. Because of medical and biopharmaceutical progress, lifespan is increasing rapidly, but healthspan is failing to keep up. If we are to increase healthy living, then we need to begin to understand the mechanisms of how we age across the life course, so that relevant interventions may be developed to facilitate “life in our years,” not simply “years in our life.” It is reported that only 25% of aging is genetically predetermined. This fits with observations of some families aging very quickly and poorly and others aging slowly and well. If this is indeed the case and the rate of aging is not fixed, then this knowledge provides a significant opportunity to manipulate the impact of environmental influencers of age. With that in mind, it begs the question of what are the mechanisms of aging and is there potential to manipulate this process on an individual-by-individual basis? The focus of this article will be on the process of muscle wasting with aging (sarcopenia) and the potential of exercise and its underlying mechanisms to reverse or delay sarcopenia. There will be a focus on epigenetics in muscle wasting and the capability of exercise to change our skeletal muscle epigenetic profile for the good. The article ends with considerations relating to facial aging, Botox treatment, and gene editing as a tool for plastic surgeons in the future.

• Hughes, David C.; Baehr, Leslie M.; Waddell, David S.; Sharples, Adam & Bodine, Sue C. (2022). Ubiquitin Ligases in Longevity and Aging Skeletal Muscle. International Journal of Molecular Sciences. ISSN 1661-6596. 23(14). doi: 10.3390/ijms23147602. Fulltekst i vitenarkiv Vis sammendrag

  The development and prevalence of diseases associated with aging presents a global health burden on society. One hallmark of aging is the loss of proteostasis which is caused in part by alterations to the ubiquitin–proteasome system (UPS) and lysosome–autophagy system leading to impaired function and maintenance of mass in tissues such as skeletal muscle. In the instance of skeletal muscle, the impairment of function occurs early in the aging process and is dependent on proteostatic mechanisms. The UPS plays a pivotal role in degradation of misfolded and aggregated proteins. For the purpose of this review, we will discuss the role of the UPS system in the context of age-related loss of muscle mass and function. We highlight the significant role that E3 ubiquitin ligases play in the turnover of key components (e.g., mitochondria and neuromuscular junction) essential to skeletal muscle function and the influence of aging. In addition, we will briefly discuss the contribution of the UPS system to lifespan. By understanding the UPS system as part of the proteostasis network in age-related diseases and disorders such as sarcopenia, new discoveries can be made and new interventions can be developed which will preserve muscle function and maintain quality of life with advancing age.

• Egan, Brendan & Sharples, Adam (2022). Molecular responses to acute exercise and their relevance for adaptations in skeletal muscle to exercise training. Physiological Reviews. ISSN 0031-9333. 103(3), s. 2057–2170. doi: 10.1152/physrev.00054.2021. Fulltekst i vitenarkiv Vis sammendrag

  Repeated, episodic bouts of skeletal muscle contraction undertaken frequently as structured exercise training is a potent stimulus for physiological adaptation in many organs. Specifically in skeletal muscle, remarkable plasticity is demonstrated by the remodeling of muscle structure and function in terms of muscular size, force, endurance, and contractile velocity as a result of the functional demands induced by various types of exercise training. This plasticity, and the mechanistic basis for adaptations to skeletal muscle in response to exercise training, is underpinned by activation and/or repression of molecular pathways and processes induced in response to each individual acute exercise session. These pathways include the transduction of signals arising from neuronal, mechanical, metabolic, and hormonal stimuli through complex signal transduction networks, which are linked to a myriad of effector proteins involved in the regulation of pre- and post-transcriptional processes, and protein translation and degradation processes. This review therefore describes acute exercise-induced signal transduction and the molecular responses to acute exercise in skeletal muscle including emerging concepts such as epigenetic pre- and post-transcriptional regulation, and the regulation of protein translation and degradation. A critical appraisal of methodological approaches and the current state of knowledge informs a series of recommendations offered as future directions in the field.

• Gorski, Piotr Patryk; Raastad, Truls; Ullrich, Max; Turner, Daniel; Hallén, Jostein & Sarvari, Sebastian [Vis alle 8 forfattere av denne artikkelen] (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. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Massar, Mohd Firdaus; Turner, Daniel C.; Gorski, Piotr Patryk; Seaborne, Robert A.; Strauss, Juliette A. & Shepherd, Sam O. [Vis alle 12 forfattere av denne artikkelen] (2021). The comparative methylome and transcriptome after change of direction compared to straight line running exercise in human skeletal muscle. Frontiers in Physiology. 12. doi: 10.3389/fphys.2021.619447. Fulltekst i vitenarkiv Vis sammendrag

  The methylome and transcriptome signature following exercise that is physiologically and metabolic relevant to sporting contexts such as team sports or health prescription scenarios (e.g. high intensity interval training/HIIT) has not been investigated. To explore this, we undertook two different sport/exercise relevant high-intensity sprint running protocols in humans using a repeated measures design of: 1) Change of direction (COD) versus; 2) straight line (ST) sprint exercise. We took skeletal muscle biopsies from the vastus lateralis 30 minutes and 24 hours post exercise followed by 850K methylation arrays and comparative analysis with recent sprint and acute aerobic exercise meta-analysis transcriptomes. Despite matched intensity (speed x distance and number of accelerations/decelerations) between COD and ST exercise, COD exercise elicited greater movement (GPS Playerload™), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) loading compared with ST exercise. The exercise response alone across both conditions evoked extensive alterations in the methylome immediately post and 24 hrs after exercise, particularly in MAPK, AMPK and axon guidance pathways. COD evoked a considerably greater hypomethylated signature across the genome compared with ST sprint exercise, particularly enriched in: Protein binding, MAPK, AMPK, insulin, and axon guidance pathways. A finding that was more prominent immediately post exercise. Comparative methylome analysis with sprint running transcriptomes identified considerable overlap, with 49% of the genes altered at the expression level also differentially methylated after COD exercise. After differential methylated region analysis, we discovered that VEGFA and its downstream nuclear transcription factor, NR4A1 had enriched hypomethylation within their promoter regions. VEGFA and NR4A1 were also significantly upregulated in the sprint transcriptome and meta-analysis of exercise transcriptomes. We confirmed increased mRNA expression of VEGFA, and considerably larger increases in the expression of canonical metabolic genes, PGC1-α and NR4A3, 3 hrs post COD vs. ST exercise. Overall, we demonstrate that increased physiological load via change of direction sprint exercise in human skeletal muscle evokes considerable epigenetic modifications that are associated with changes in expression of genes responsible for adaptation to exercise. These data imply that introducing changes in direction into high intensity running protocols could serve as an important modulator of a favourable epigenomic and transcriptomic landscape in response to exercise in athletes and trigger greater skeletal muscle remodelling through enhanced gene expression.

• Voisin, Sarah; Jacques, Macsue; Landen, Shanie; Harvey, Nicholas R.; Haupt, Larisa M. & Griffiths, Lyn R. [Vis alle 28 forfattere av denne artikkelen] (2021). Meta-analysis of genome-wide DNA methylation and integrative omics of age in human skeletal muscle. Journal of Cachexia, Sarcopenia and Muscle. ISSN 2190-5991. 12(4), s. 1064–1078. doi: 10.1002/jcsm.12741. Fulltekst i vitenarkiv Vis sammendrag

  Background: Knowledge of age-related DNA methylation changes in skeletal muscle is limited, yet this tissue is se-verely affected by ageing in humans. Methods: We conducted a large-scale epigenome-wide association study meta-analysis of age in human skeletalmuscle from 10 studies (total n ¼ 908 muscle methylomes from men and women aged 18–89 years old). We exploredthe genomic context of age-related DNA methylation changes in chromatin states, CpG islands, and transcription factorbinding sites and performed gene set enrichment analysis. We then integrated the DNA methylation data with knowntranscriptomic and proteomic age-related changes in skeletal muscle. Finally, we updated our recently developedmuscle epigenetic clock (https://bioconductor.org/packages/release/bioc/html/MEAT.html).Results: We identied 6710 differentially methylated regions at a stringent false discovery rate <0.005, spanning 6367unique genes, many of which related to skeletal muscle structure and development. We found a strong increase in DNAmethylation at Polycomb target genes and bivalent chromatin domains and a concomitant decrease in DNA methylationat enhancers. Most differentially methylated genes were not altered at the mRNA or protein level, but they were none-theless strongly enriched for genes showing age-related differential mRNA and protein expression. After adding a sub-stantial number of samples from ve datasets (+371), t he updated version of the muscle clock (MEAT 2.0, totaln ¼ 1053 samples) performed similarly to the original version of the muscle clock (median of 4.4 vs. 4.6 years inage prediction error), suggesting that the original version of the muscle clock was very accurate.Conclusions: We provide here the most comprehensive picture of DNA methylation ageing in human skeletal muscleand reveal widespread alterations of genes involved in skeletal muscle structure, development, and differentiation.We have made our results available as an open-access, user-friendly, web-based tool called MetaMeth (https://sarah-voisin.shinyapps.io/MetaMeth/)

• Hughes, David C.; Turner, Daniel; Baehr, Leslie M; Seaborne, Robert A.; Viggars, Mark & Jarvis, Jonathan C. [Vis alle 11 forfattere av denne artikkelen] (2021). Knockdown of the E3 Ubiquitin ligase UBR5 and its role in skeletal muscle anabolism. American Journal of Physiology - Cell Physiology. 320(1), s. C45–C56. doi: 10.1152/AJPCELL.00432.2020. Fulltekst i vitenarkiv Vis sammendrag

  UBR5 is an E3-ubiquitin-ligase positively associated with anabolism, hypertrophy and recovery from atrophy in skeletal muscle. The precise mechanisms underpinning UBR5's role in the regulation of skeletal muscle mass remains unknown. The present study aimed to elucidate these mechanisms by silencing the UBR5 gene in-vivo. To achieve this aim, we electroporated a UBR5-RNAi plasmid into mouse tibialis anterior muscle to investigate the impact of reduced UBR5 on mechano-transduction signalling MEK/ERK/p90RSK and Akt/GSK3β/p70S6K/4E-BP1/rpS6 pathways. Seven days post UBR5 RNAi electroporation, while reductions in overall muscle mass were not detected, mean CSA of GFP-positive fibers was reduced (-9.5%) and the number of large fibers was lower versus the control. Importantly, UBR5-RNAi significantly reduced total RNA, muscle protein synthesis, ERK1/2, Akt and GSK3β activity. Whilst p90RSK phosphorylation significantly increased, total p90RSK protein levels demonstrated a 45% reduction with UBR5-RNAi. Finally, these early events after 7 days of UBR5 knockdown culminated in significant reductions in muscle mass (-4.6%) and larger reductions in fiber CSA (-18.5%) after 30 days. This was associated with increased levels of the phosphatase PP2Ac, and inappropriate chronic elevation of p70S6K and rpS6 between 7 and 30 days, and corresponding reductions in eIF4e. This study demonstrates UBR5 plays an important role in anabolism/hypertrophy, whereby knockdown of UBR5 culminates in skeletal muscle atrophy.

• Ruple, Bradley A; Godwin, Joshua S.; Mesquita, Paulo H. C; Osburn, Shelby C; Vann, Christopher G & Lamb, Donald A [Vis alle 15 forfattere av denne artikkelen] (2021). Resistance training rejuvenates the mitochondrial methylome in aged human skeletal muscle. The FASEB Journal. ISSN 0892-6638. 35(9). doi: 10.1096/fj.202100873RR. Fulltekst i vitenarkiv Vis sammendrag

  Resistance training (RT) dynamically alters the skeletal muscle nuclear DNA methylome. However, no study has examined if RT affects the mitochondrial DNA (mtDNA) methylome. Herein, ten older, Caucasian untrained males (65 ± 7 y.o.) performed six weeks of full-body RT (twice weekly). Body composition and knee extensor torque were assessed prior to and 72 h following the last RT session. Vastus lateralis (VL) biopsies were also obtained. VL DNA was subjected to reduced representation bisulfite sequencing providing excellent coverage across the ~16-kilobase mtDNA methylome (254 CpG sites). Biochemical assays were also performed, and older male data were compared to younger trained males (22 ± 2 y.o., n = 7, n = 6 Caucasian & n = 1 African American). RT increased whole-body lean tissue mass (p = .017), VL thickness (p = .012), and knee extensor torque (p = .029) in older males. RT also affected the mtDNA methylome, as 63% (159/254) of the CpG sites demonstrated reduced methylation (p

• Sharples, Adam (2021). Skeletal Muscle Possesses an Epigenetic Memory of Exercise: Role of Nucleus Type-Specific DNA Methylation. Function. 2(5). doi: 10.1093/function/zqab047. Fulltekst i vitenarkiv
• Turner, Daniel C.; Gorski, Piotr Patryk; Seaborne, Robert A.; Viggars, Mark; Murphy, Mark & Jarvis, Jonathan C. [Vis alle 9 forfattere av denne artikkelen] (2021). Mechanical loading of bioengineered skeletal muscle in vitro recapitulates gene expression signatures of resistance exercise in vivo. Journal of Cellular Physiology. ISSN 0021-9541. 236(9), s. 6534–6547. doi: 10.1002/jcp.30328. Fulltekst i vitenarkiv Vis sammendrag

  Understanding the role of mechanical loading and exercise in skeletal muscle (SkM) is paramount for delineating the molecular mechanisms that govern changes in muscle mass. However, it is unknown whether loading of bioengineered SkM in vitro adequately recapitulates the molecular responses observed after resistance exercise (RE) in vivo. To address this, the transcriptional and epigenetic (DNA methylation) responses were compared after mechanical loading in bioengineered SkM in vitro and after RE in vivo. Specifically, genes known to be upregulated/hypomethylated after RE in humans were analyzed. Ninety-three percent of these genes demonstrated similar changes in gene expression post-loading in the bioengineered muscle when compared to acute RE in humans. Furthermore, similar differences in gene expression were observed between loaded bioengineered SkM and after programmed RT in rat SkM tissue. Hypomethylation occurred for only one of the genes analysed (GRIK2) post-loading in bioengineered SkM. To further validate these findings, DNA methylation and mRNA expression of known hypomethylated and upregulated genes post-acute RE in humans were also analyzed at 0.5, 3, and 24 h post-loading in bioengineered muscle. The largest changes in gene expression occurred at 3 h, whereby 82% and 91% of genes responded similarly when compared to human and rodent SkM respectively. DNA methylation of only a small proportion of genes analyzed (TRAF1, MSN, and CTTN) significantly increased post-loading in bioengineered SkM alone. Overall, mechanical loading of bioengineered SkM in vitro recapitulates the gene expression profile of human and rodent SkM after RE in vivo. Although some genes demonstrated differential DNA methylation post-loading in bioengineered SkM, such changes across the majority of genes analyzed did not closely mimic the epigenetic response to acute-RE in humans.

• Turner, Daniel C.; Gorski, Piotr Patryk; Massar, Mohd Firdaus; Seaborne, Robert A.; Baumert, Phillipp & Brown, Alexander D. [Vis alle 22 forfattere av denne artikkelen] (2020). DNA methylation across the genome in aged human skeletal muscle tissue and muscle-derived cells: the role of HOX genes and physical activity. Scientific Reports. 10(1). doi: 10.1038/s41598-020-72730-z. Fulltekst i vitenarkiv Vis sammendrag

  Skeletal muscle tissue demonstrates global hypermethylation with age. However, methylome changes across the time-course of differentiation in aged human muscle derived cells, and larger coverage arrays in aged muscle tissue have not been undertaken. Using 850K DNA methylation arrays we compared the methylomes of young (27 ± 4.4 years) and aged (83 ± 4 years) human skeletal muscle and that of young/aged heterogenous muscle-derived human primary cells (HDMCs) over several time points of differentiation (0, 72 h, 7, 10 days). Aged muscle tissue was hypermethylated compared with young tissue, enriched for; pathways-in-cancer (including; focal adhesion, MAPK signaling, PI3K-Akt-mTOR signaling, p53 signaling, Jak-STAT signaling, TGF-beta and notch signaling), rap1-signaling, axon-guidance and hippo-signalling. Aged cells also demonstrated a hypermethylated profile in pathways; axon-guidance, adherens-junction and calcium-signaling, particularly at later timepoints of myotube formation, corresponding with reduced morphological differentiation and reductions in MyoD/Myogenin gene expression compared with young cells. While young cells showed little alterations in DNA methylation during differentiation, aged cells demonstrated extensive and significantly altered DNA methylation, particularly at 7 days of differentiation and most notably in focal adhesion and PI3K-AKT signalling pathways. While the methylomes were vastly different between muscle tissue and HDMCs, we identified a small number of CpG sites showing a hypermethylated state with age, in both muscle tissue and cells on genes KIF15, DYRK2, FHL2, MRPS33, ABCA17P. Most notably, differential methylation analysis of chromosomal regions identified three locations containing enrichment of 6–8 CpGs in the HOX family of genes altered with age. With HOXD10, HOXD9, HOXD8, HOXA3, HOXC9, HOXB1, HOXB3, HOXC-AS2 and HOXC10 all hypermethylated in aged tissue. In aged cells the same HOX genes (and additionally HOXC-AS3) displayed the most variable methylation at 7 days of differentiation versus young cells, with HOXD8, HOXC9, HOXB1 and HOXC-AS3 hypermethylated and HOXC10 and HOXC-AS2 hypomethylated. We also determined that there was an inverse relationship between DNA methylation and gene expression for HOXB1, HOXA3 and HOXC-AS3. Finally, increased physical activity in young adults was associated with oppositely regulating HOXB1 and HOXA3 methylation compared with age. Overall, we demonstrate that a considerable number of HOX genes are differentially epigenetically regulated in aged human skeletal muscle and HDMCs and increased physical activity may help prevent age-related epigenetic changes in these HOX genes.

• Seaborne, Robert A. & Sharples, Adam (2020). The interplay between exercise metabolism, epigenetics, and skeletal muscle remodeling. Exercise and sport sciences reviews. ISSN 0091-6331. 48(4), s. 188–200. doi: 10.1249/JES.0000000000000227. Fulltekst i vitenarkiv Vis sammendrag

  We explore work from within the field of skeletal muscle and across the broader field of molecular biology, to propose that the link between exercise and skeletal muscle adaptation lies in the interplay between metabolism and epigenetics. Future investigations into such an interaction are crucial to advance our understanding of the beneficial effects of exercise on performance and health.

• Hearris, Mark A.; Owens, Daniel J.; Strauss, Juliette A.; Shepherd, Sam O.; Sharples, Adam & Morton, James P. [Vis alle 7 forfattere av denne artikkelen] (2020). Graded reductions in pre-exercise glycogen concentration do not augment exercise-induced nuclear AMPK and PGC-1α protein content in human muscle. Experimental Physiology. ISSN 0958-0670. doi: 10.1113/EP088866. Fulltekst i vitenarkiv Vis sammendrag

  We examined the effects of graded muscle glycogen on the subcellular location and protein content of AMP‐activated protein kinase (AMPK) and peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) and mRNA expression of genes associated with the regulation of mitochondrial biogenesis and substrate utilisation in human skeletal muscle. In a repeated measures design, eight trained male cyclists completed acute high‐intensity interval (HIT) cycling (8 × 5 min at 80% peak power output) with graded concentrations of pre‐exercise muscle glycogen. Following initial glycogen‐depleting exercise, subjects ingested 2 g kg−1 (L‐CHO), 6 g kg−1 (M‐CHO) or 14 g kg−1 (H‐CHO) of carbohydrate during a 36 h period, such that exercise was commenced with graded (P < 0.05) muscle glycogen concentrations (mmol (kg dw)−1: H‐CHO, 531 ± 83; M‐CHO, 332 ± 88; L‐CHO, 208 ± 79). Exercise depleted muscle glycogen to <300 mmol (kg dw)−1 in all trials (mmol (kg dw)−1: H‐CHO, 270 ± 88; M‐CHO, 173 ± 74; L‐CHO, 100 ± 42) and induced comparable increases in nuclear AMPK protein content (∼2‐fold) and PGC‐1α (∼5‐fold), p53 (∼1.5‐fold) and carnitine palmitoyltransferase 1 (∼2‐fold) mRNA between trials (all P < 0.05). The magnitude of increase in PGC‐1α mRNA was also positively correlated with post‐exercise glycogen concentration (P < 0.05). In contrast, neither exercise nor carbohydrate availability affected the subcellular location of PGC‐1α protein or PPAR, SCO2, SIRT1, DRP1, MFN2 or CD36 mRNA. Using a sleep‐low, train‐low model with a high‐intensity endurance exercise stimulus, we conclude that pre‐exercise muscle glycogen does not modulate skeletal muscle cell signalling.

• Allan, Robert; Morton, James P.; Close, Graeme L.; Drust, Barry; Gregson, Warren & Sharples, Adam (2020). PGC-1α alternative promoter (Exon 1b) controls augmentation of total PGC-1α gene expression in response to cold water immersion and low glycogen availability. European Journal of Applied Physiology. ISSN 1439-6319. 120(11), s. 2487–2493. doi: 10.1007/s00421-020-04467-6. Fulltekst i vitenarkiv Vis sammendrag

  This investigation sought to determine whether post-exercise cold water immersion and low glycogen availability, separately and in combination, would preferentially activate either the Exon 1a or Exon 1b Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) promoter. Through a reanalysis of sample design, we identified that the systemic cold-induced augmentation of total PGC-1α gene expression observed previously (Allan et al. in J Appl Physiol 123(2):451–459, 2017) was largely a result of increased expression from the alternative promoter (Exon 1b), rather than canonical promoter (Exon 1a). Low glycogen availability in combination with local cooling of the muscle (Allan et al. in Physiol Rep 7(11):e14082, 2019) demonstrated that PGC-1α alternative promoter (Exon 1b) expression continued to rise at 3 h post-exercise in all conditions; whilst, expression from the canonical promoter (Exon 1a) decreased between the same time points (post-exercise–3 h post-exercise). Importantly, this increase in PGC-1α Exon 1b expression was reduced compared to the response of low glycogen or cold water immersion alone, suggesting that the combination of prior low glycogen and CWI post-exercise impaired the response in gene expression versus these conditions individually. Data herein emphasise the influence of post-exercise cooling and low glycogen availability on Exon-specific control of total PGC-1 α gene expression and highlight the need for future research to assess Exon-specific regulation of PGC-1α.

• Voisin, Sarah; Harvey, Nicholas R; Haupt, Larisa M; Griffiths, Lyn R; Aston, Kevin J & Coffey, Vernon G. [Vis alle 16 forfattere av denne artikkelen] (2020). An epigenetic clock for human skeletal muscle. Journal of Cachexia, Sarcopenia and Muscle. ISSN 2190-5991. 11(4), s. 887–898. doi: 10.1002/jcsm.12556. Fulltekst i vitenarkiv Vis sammendrag

  Background: Ageing is associated with DNA methylation changes in all human tissues, and epigenetic markers can estimate chronological age based on DNA methylation patterns across tissues. However, the construction of the original pan‐tissue epigenetic clock did not include skeletal muscle samples and hence exhibited a strong deviation between DNA methylation and chronological age in this tissue. Methods: To address this, we developed a more accurate, muscle‐specific epigenetic clock based on the genome‐wide DNA methylation data of 682 skeletal muscle samples from 12 independent datasets (18–89 years old, 22% women, 99% Caucasian), all generated with Illumina HumanMethylation (HM) arrays (HM27, HM450, or HMEPIC). We also took advantage of the large number of samples to conduct an epigenome‐wide association study of age‐associated DNA methylation patterns in skeletal muscle. Results: The newly developed clock uses 200 cytosine‐phosphate–guanine dinucleotides to estimate chronological age in skeletal muscle, 16 of which are in common with the 353 cytosine‐phosphate–guanine dinucleotides of the pan‐tissue clock. The muscle clock outperformed the pan‐tissue clock, with a median error of only 4.6 years across datasets (vs. 13.1 years for the pan‐tissue clock, P < 0.0001) and an average correlation of ρ = 0.62 between actual and predicted age across datasets (vs. ρ = 0.51 for the pan‐tissue clock). Lastly, we identified 180 differentially methylated regions with age in skeletal muscle at a false discovery rate < 0.005. However, gene set enrichment analysis did not reveal any enrichment for gene ontologies. Conclusions: We have developed a muscle‐specific epigenetic clock that predicts age with better accuracy than the pan‐tissue clock. We implemented the muscle clock in an r package called Muscle Epigenetic Age Test available on Bioconductor to estimate epigenetic age in skeletal muscle samples. This clock may prove valuable in assessing the impact of environmental factors, such as exercise and diet, on muscle‐specific biological ageing processes.

• Turner, Daniel C.; Kasper, Andreas M.; Seaborne, Robert A.; Brown, Alexander D.; Close, Graeme L. & Murphy, Mark [Vis alle 9 forfattere av denne artikkelen] (2019). Exercising Bioengineered Skeletal Muscle in-vitro: Biopsy to Bioreactor. Methods in molecular biology. ISSN 1064-3745. 1889, s. 55–79. doi: 10.1007/978-1-4939-8897-6_5. Fulltekst i vitenarkiv
• Sharples, Adam & Seaborne, Robert A. (2019). Exercise and DNA methylation in skeletal muscle. I Barh, Debmalya & Ahmetov, Ildus I. (Red.), Sports, Exercise, and Nutritional Genomics : Current Status and Future Directions. Elsevier. ISSN 9780128161937. s. 211–229. doi: 10.1016/B978-0-12-816193-7.00010-5. Fulltekst i vitenarkiv
• Hammond, Kelly M.; Sale, Craig; Fraser, William; Tang, Jonathan; Shepherd, Sam O. & Strauss, Juliette A. [Vis alle 13 forfattere av denne artikkelen] (2019). Post-exercise carbohydrate and energy availability induce independent effects on skeletal muscle cell signalling and bone turnover: implications for training adaptation. Journal of Physiology. ISSN 0022-3751. 597(18), s. 4779–4796. doi: 10.1113/JP278209. Fulltekst i vitenarkiv
• Hearris, Mark A.; Hammond, Kelly M.; Seaborne, Robert A.; Stocks, Ben; Shepherd, Sam O. & Philp, Andrew [Vis alle 9 forfattere av denne artikkelen] (2019). Graded reductions in pre-exercise muscle glycogen impair exercise capacity but do not augment cell skeletal muscle signalling: implication for CHO periodisation. Journal of applied physiology. ISSN 8750-7587. 126(6), s. 1587–1597. doi: 10.1152/japplphysiol.00913.2018. Fulltekst i vitenarkiv
• Allan, Robert; Sharples, Adam; Cocks, Matt; Drust, Barry; Dutton, John & Dugdale, Hannah F. [Vis alle 11 forfattere av denne artikkelen] (2019). Low pre-exercise muscle glycogen availability offsets the effect of post-exercise cold water immersion in augmenting PGC-1α gene expression. Physiological Reports. 7(11), s. e14082–e14082. doi: 10.14814/phy2.14082. Fulltekst i vitenarkiv
• Seaborne, Robert A.; Hughes, David C.; Turner, Daniel C.; Owens, Daniel J.; Baehr, Leslie M & Gorski, Piotr [Vis alle 16 forfattere av denne artikkelen] (2019). UBR5 is a novel E3 ubiquitin ligase involved in skeletal muscle hypertrophy and recovery from atrophy. Journal of Physiology. ISSN 0022-3751. 597(14), s. 3727–3749. doi: 10.1113/JP278073. Fulltekst i vitenarkiv
• Turner, Daniel C.; Seaborne, Robert A. & Sharples, Adam (2019). Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle Anabolism, Hypertrophy and Epigenetic Memory. Scientific Reports. 9. doi: 10.1038/s41598-019-40787-0. Fulltekst i vitenarkiv
• Dugdale, Hannah F.; Hughes, David C.; Allan, Robert; Deane, Colleen S; Coxon, Christopher R & Morton, James P. [Vis alle 8 forfattere av denne artikkelen] (2018). The role of resveratrol on skeletal muscle cell differentiation and myotube hypertrophy during glucose restriction. Molecular and Cellular Biochemistry. ISSN 0300-8177. 444(1-2), s. 109–123. doi: 10.1007/s11010-017-3236-1. Fulltekst i vitenarkiv
• Impey, Sam G.; Hammond, Kelly M.; Naughton, R; Langen-Evans, Carl; Shepherd, Sam O. & Sharples, Adam [Vis alle 12 forfattere av denne artikkelen] (2018). Whey protein augments leucinemia and post-exercise p70S6K1 activity compared to a hydrolysed collagen blend when in recovery from training with low carbohydrate availability. International Journal of Sport Nutrition & Exercise Metabolism. ISSN 1526-484X. 8(6), s. 651–659. doi: 10.1123/ijsnem.2018-0054. Fulltekst i vitenarkiv
• Seaborne, Robert A.; Strauss, J; Cocks, Matt; Shepherd, Sam O.; O'brien, Thomas D. & Someren, Ken A. van [Vis alle 11 forfattere av denne artikkelen] (2018). Human Skeletal Muscle Possesses an Epigenetic Memory of Hypertrophy. Scientific Reports. 8(1). doi: 10.1038/s41598-018-20287-3. Fulltekst i vitenarkiv
• Seaborne, Robert A.; Strauss, Juliette A.; Cocks, Matt; Shepherd, Sam O.; O'brien, Thomas D. & Someren, Ken A. van [Vis alle 11 forfattere av denne artikkelen] (2018). Methylome of Human Skeletal Muscle after Acute & Chronic Resistance Exercise Training, Detraining & Retraining. Scientific Data. 5, Article 180213. doi: 10.1038/sdata.2018.213. Fulltekst i vitenarkiv
• Kasper, Andy M.; Turner, Daniel C.; Martin, Neil R.W. & Sharples, Adam (2017). Mimicking exercise in three-dimensional bioengineered skeletal muscle to investigate the cellular and molecular mechanisms of physiological adaptation. Journal of Cellular Physiology. ISSN 0021-9541. 233(3), s. 1985–1998. doi: 10.1002/jcp.25840. Fulltekst i vitenarkiv
• Brown, Alexander D.; Close, Graeme L.; Sharples, Adam & Stewart, Claire (2017). Murine Myoblast Migration: Influence of Replicative Ageing & Nutrition. Biogerontology (Dordrecht). ISSN 1389-5729. 18(6), s. 947–964. doi: 10.1007/s10522-017-9735-3. Fulltekst i vitenarkiv
• Allan, Robert; Sharples, Adam; Close, Graeme L.; Drust, Barry; Shepherd, Sam O. & Dutton, John [Vis alle 8 forfattere av denne artikkelen] (2017). Postexercise cold water immersion modulates skeletal muscle PGC-1α mRNA expression in immersed and nonimmersed limbs: evidence of systemic regulation. Journal of applied physiology. ISSN 8750-7587. 123(2), s. 451–459. doi: 10.1152/japplphysiol.00096.2017. Fulltekst i vitenarkiv
• Fisher, Andrew G.; Seaborne, Robert A.; Hughes, Thomas M.; Gutteridge, Andrew; Stewart, C & Coulson, J [Vis alle 8 forfattere av denne artikkelen] (2017). Transcriptomic and Epigenetic Regulation of Skeletal Muscle Disuse Atrophy and Recovery. The FASEB Journal. ISSN 0892-6638. 31(12), s. 5268–5282. doi: 10.1096/fj.201700089RR. Fulltekst i vitenarkiv
• Sharples, Adam (2016). L-glutamine improves skeletal muscle cell differentiation and prevents myotube atrophy after cytokine (TNF-α) stress via reduced p38 MAPK signal transduction. Journal of Cellular Physiology. ISSN 0021-9541. 231(12), s. 2720–2732. doi: 10.1002/jcp.25380. Fulltekst i vitenarkiv
• Sharples, Adam (2016). Omega-3 fatty acid EPA improves regenerative capacity of mouse skeletal muscle cells exposed to saturated fat and inflammation. Biogerontology (Dordrecht). ISSN 1389-5729. 18(1), s. 109–129. doi: 10.1007/s10522-016-9667-3. Fulltekst i vitenarkiv
• Sharples, Adam (2016). Skeletal muscle cells possess a memory of acute early life TNF-α exposure: Role of epigenetic adaptation. Biogerontology (Dordrecht). ISSN 1389-5729. 17(3), s. 603–617. doi: 10.1007/s10522-015-9604-x. Fulltekst i vitenarkiv
• Sharples, Adam (2016). Does skeletal muscle have an ‘epi’-memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise. Aging Cell. ISSN 1474-9718. 15(4), s. 603–616. doi: 10.1111/acel.12486. Fulltekst i vitenarkiv
• Sharples, Adam (2016). Fuel for the work required: A practical approach to amalgamating train-low paradigms for endurance athletes. Physiological Reports. 4(10), s. e12803–e12803. doi: 10.14814/phy2.12803. Fulltekst i vitenarkiv
• Sharples, Adam (2016). Post exercise high-fat feeding supresses p70S6K1 activity in human skeletal muscle. Medicine & Science in Sports & Exercise. ISSN 0195-9131. 48(11), s. 2108–2117. doi: 10.1249/MSS.0000000000001009. Fulltekst i vitenarkiv
• Sharples, Adam (2015). Longevity and Skeletal Muscle Mass: The role of IGF signalling, the Sirtuins, dietary restriction and protein intake. Aging Cell. ISSN 1474-9718. 14(4), s. 511–523. doi: 10.1111/acel.12342. Fulltekst i vitenarkiv
• Sharples, Adam (2015). Testosterone enables growth & hypertrophy in fusion impaired myoblasts that display myotube atrophy: deciphering the role of androgen & IGF-I receptors. Biogerontology (Dordrecht). ISSN 1389-5729. 17(3), s. 619–639. doi: 10.1007/s10522-015-9621-9. Fulltekst i vitenarkiv
• Sharples, Adam (2015). A Systems Based Investigation into Vitamin D and Skeletal Muscle Repair, Regeneration and Hypertrophy. American Journal of Physiology. Endocrinology and Metabolism. ISSN 0193-1849. 309(12), s. E1019–1031. doi: 10.1152/ajpendo.00375.2015. Fulltekst i vitenarkiv
• Sharples, Adam (2014). Acute mechanical overload increases IGF-I & MMP-9 mRNA in 3D tissue-engineered skeletal muscle. Biotechnology Letters. ISSN 0141-5492. 36(5), s. 1113–1124. doi: 10.1007/s10529-014-1464-y. Fulltekst i vitenarkiv
• Sharples, Adam (2013). Impaired hypertrophy in myoblasts is improved with testosterone administration. Journal of Steroid Biochemistry and Molecular Biology. ISSN 0960-0760. 138, s. 152–161. doi: 10.1016/j.jsbmb.2013.05.005. Fulltekst i vitenarkiv
• Sharples, Adam (2013). The role of insulin-like-growth factor binding protein 2 (IGFBP2) and phosphatase and tensin homologue (PTEN) in the regulation of myoblast differentiation and hypertrophy. Growth Hormone & IGF Research. ISSN 1096-6374. 23(3). doi: 10.1016/j.ghir.2013.03.004. Fulltekst i vitenarkiv
• Sharples, Adam (2013). Factors affecting the structure and maturation of human tissue engineered skeletal muscle. Biomaterials. ISSN 0142-9612. 34(23), s. 5759–5765. doi: 10.1016/j.biomaterials.2013.04.002. Fulltekst i vitenarkiv
• Sharples, Adam (2012). Modelling in vivo skeletal muscle ageing in vitro using three-dimensional bioengineered constructs. Aging Cell. ISSN 1474-9718. 11(6), s. 986–995. doi: 10.1111/j.1474-9726.2012.00869.x. Fulltekst i vitenarkiv
• Sharples, Adam (2012). Sirtuin 1 regulates skeletal myoblast survival and enhances differentiation in the presence of resveratrol. Experimental Physiology. ISSN 0958-0670. 97(3). doi: 10.1113/expphysiol.2011.061028. Fulltekst i vitenarkiv
• Sharples, Adam (2011). Myoblast models of skeletal muscle hypertrophy and atrophy. Current opinion in clinical nutrition and metabolic care. ISSN 1363-1950. 14(3). doi: 10.1097/MCO.0b013e3283457ade. Fulltekst i vitenarkiv
• Sharples, Adam (2011). Reduction of myoblast differentiation following multiple population doublings in mouse C2C12 cells: a model to investigate ageing? Journal of Cellular Biochemistry. ISSN 0730-2312. 112(12), s. 3773–3785. doi: 10.1002/jcb.23308. Fulltekst i vitenarkiv
• Sharples, Adam (2010). C2 and C2C12 murine skeletal myoblast models of atrophic and hypertrophic potential: relevance to disease and ageing? Journal of Cellular Physiology. ISSN 0021-9541. 225(1), s. 240–250. doi: 10.1002/jcp.22252. Fulltekst i vitenarkiv
• Sharples, Adam (2008). Postprandial triacylglycerol in boys: a case for moderate exercise. Medicine & Science in Sports & Exercise. ISSN 0195-9131. 6(40), s. 1049–1056. doi: 10.1249/MSS.0b013e31816770fe. Fulltekst i vitenarkiv

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• Sharples, Adam; Morton, James P & Wackerhage, Henning (2022). Molecular Exercise Physiology: An Introduction (Second Edition). Routledge. ISBN 9781315110752. 358 s. Fulltekst i vitenarkiv Vis sammendrag

  Fully revised and expanded, the second edition of Molecular Exercise Physiology offers a student-friendly introduction. It introduces a history documenting the emergence of molecular biology techniques to investigate exercise physiology, the methodology used, exercise genetics and epigenetics, and the molecular mechanisms that lead to adaptation after different types of exercise, with explicit links to outcomes in sport performance, nutrition, physical activity and clinical exercise. Structured around key topics in sport and exercise science and featuring contributions from pioneering scientists, such as Nobel Prize winners, this edition includes new chapters based on cutting-edge research in epigenetics and muscle memory, satellite cells, exercise in cancer, at altitude, and in hot and cold climates. Chapters include learning objectives, structured guides to further reading, review questions, overviews of work by key researchers and box discussions from important pioneers in the field, making it a complete resource for any molecular exercise physiology course. The book includes cell and molecular biology laboratory methods for dissertation and research projects in molecular exercise physiology and muscle physiology. This book is essential reading for upper-level undergraduate or postgraduate courses in cellular and molecular exercise physiology and muscle physiology. It is a valuable resource for any student with an advanced interest in exercise physiology in both sport performance and clinical settings. Adam P. Sharples, PhD, is a Professor of Molecular Physiology and Epigenetics at the Norwegian School of Sport Sciences (NiH), Olso, Norway; an institute ranked 2nd (out of 300+) in the world for sport and exercise sciences. He investigates the underlying cellular, molecular and epigenetic mechanisms of muscle growth (hypertrophy) and wasting (atrophy) using both cell modelling and whole-body approaches. His work first demonstrated that human muscle possesses an “epigenetic memory” of exercise. He used to play professional Rugby League in the UK. James P. Morton, PhD, is a Professor of Exercise Metabolism at Liverpool John Moores University (LJMU). His research evaluates the impact of nutrient availability on muscle metabolism during exercise and the molecular regulation of skeletal muscle adaptations to exercise training. James has also worked in a number of performance related roles across both high-performance sport and industry, working with some of the world’s most high profile athletes, sports teams and institutions. Henning Wackerhage, PhD, is a Professor and Molecular Exercise Physiologist. He is specifically interested in the molecular mechanisms by which exercise improves our fitness and health, particularly the role of the so-called Hippo proteins in skeletal muscle and the association between the proteome, metabolome, athletic performance, disease and ageing.

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• Sharples, Adam P. (2026). Your Muscles Retain Memories of Strength and Weakness. [Internet]. Yahoo News. doi: https:/www.yahoo.com/news/articles/muscles-retain-memories-strength-weakness-193208330.html. Fulltekst i vitenarkiv
• Sharples, Adam P. & Tsui, Bonnie (2026). A Different Type of ‘Muscle Memory’. [Journal]. The Atlantic. doi: https:/www.theatlantic.com/health/2026/01/muscle-memory/685602/. Fulltekst i vitenarkiv Vis sammendrag

  Repeated exercise, or wasting, can change the way key genes work.

• Sharples, Adam P. & Dyregrov, Silje (2026). Magne (34) «lekte» at han var skadet i studie. Nå har forskerne fått nye svar om muskelminne. – Dette er helt nytt på verdensbasis og noe ingen kjente til fra før, sier professor. [Journal]. Bergens Tidende. doi: https:/www.bt.no/sprek/i/M7o7dK/magne-lund-hansen-31-lekte-at-han-var-skadet-i-studie-naa-har-forskerne-faatt-nye-svar-om-muskelminne. Fulltekst i vitenarkiv
• Sharples, Adam P. & Dyregrov, Silje (2026). Magne Lund-Hansen (34) «lekte» at han var skadet i studie. Nå har forskerne fått nye svar om muskelminne. – Dette er helt nytt på verdensbasis og noe ingen kjente til fra før, sier professor. [Journal]. Aftenposten. doi: https:/www.aftenposten.no/sprek/i/Pd4d06/magne-lund-hansen-34-lekte-at-han-var-skadet-i-studie-naa-har-forskerne-faatt-nye-svar-om-muskelminne. Fulltekst i vitenarkiv
• Sharples, Adam P. & Landwehr, Tobias (2025). Skateboarden, Fahrradfahren oder Tennis: einmal gelernt und nie wieder vergessen – wie schafft der Körper das? [Journal]. NZZ. doi: https:/www.nzz.ch/sport/sportarten-einmal-gelernt-und-nie-wieder-vergessen-wie-schafft-der-koerper-das-ld.1870672. Fulltekst i vitenarkiv
• Sharples, Adam P. & Dyregrov, Silje (2025). Ny studie om testosteron: – Bør vurdere å endre bruken hvis funnene bekreftes, mener professor. [Journal]. Aftenposten. doi: https:/www.aftenposten.no/sprek/i/aloEqd/ny-studie-om-testosteron-boer-vurdere-aa-endre-bruken-hvis-funnene-bekreftes-mener-professor. Fulltekst i vitenarkiv
• Sharples, Adam P. & Tsui, Bonnie (2025). Muscle Memory Isn’t What You Think It Is. [Journal]. Wired Magazine. doi: https:/www.wired.com/story/book-excerpt-on-muscle-bonnie-tsui/. Fulltekst i vitenarkiv
• Sharples, Adam P. (2025). Flex appeal: how our muscles make us human. doi: https:/www.theguardian.com/science/2025/apr/20/flex-appeal-how-our-muscles-makes-us-human. Fulltekst i vitenarkiv
• Sharples, Adam P. & Tømmerbakke, Daniel (2024). Tommy (56): – Trodde aldri jeg skulle begynne med doping. [TV]. TV2. doi: https:/www.tv2.no/nyheter/innenriks/tommy-56-trodde-aldri-jeg-skulle-begynne-med-doping/16967658/. Fulltekst i vitenarkiv
• Nilsen, Tormod Skogstad; Sæter, Mali; Sarvari, Sebastian; Reinertsen, Kristin Valborg; Johansen, Sara Hassing & Edvardsen, Elisabeth Rustad [Vis alle 17 forfattere av denne artikkelen] (2023). Effects of Aerobic Exercise on Cardiorespiratory Fitness, Cardiovascular Risk Factors, and Patient-Reported Outcomes in Long-Term Breast Cancer Survivors: Protocol for a Randomized Controlled Trial. JMIR Research Protocols. 12. doi: 10.2196/45244. Fulltekst i vitenarkiv Vis sammendrag

  Background Anthracycline-based chemotherapy has been mainstay of adjuvant breast cancer therapy for decades. Although effective, anthracyclines place long-term breast cancer survivors at risk of late effects, such as reduced cardiorespiratory fitness and increased risk of cardiovascular disease. Previous research has shown beneficial effects of exercise training on cardiorespiratory fitness, but the effects of exercise on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes in long-term survivors are less clear. Whether previous exposure to breast cancer therapy modulates the effects of exercise is also unknown. Objective The primary aim of the CAUSE (Cardiovascular Survivors Exercise) trial is to examine the effect of aerobic exercise on cardiorespiratory fitness in anthracycline-treated long-term breast cancer survivors. Secondary aims are to examine effects of exercise training on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes, and to compare baseline values and effects of exercise training between similar-aged women with and those without prior breast cancer. A third aim is to examine the 24-month postintervention effects of aerobic exercise on primary and secondary outcomes. Methods The CAUSE trial is a 2-armed randomized controlled trial, where 140 long-term breast cancer survivors, 8-12 years post diagnosis, are assigned to a 5-month nonlinear aerobic exercise program with 3 weekly sessions or to standard care. Seventy similar-aged women with no history of cancer will undergo the same exercise program. Cardiorespiratory fitness measured as peak oxygen consumption (VO2peak), limiting factors for VO2peak (eg, cardiac function, pulmonary function, hemoglobin mass, blood volume, and skeletal muscle characteristics), cardiovascular risk factors (eg, hypertension, diabetes, dyslipidemia, obesity, physical activity level, and smoking status), and patient-reported outcomes (eg, body image, fatigue, mental health, and health-related quality of life) will be assessed at baseline, post intervention, and 24 months post intervention. Results A total of 209 patients were included from October 2020 to August 2022, and postintervention assessments were completed in January 2023. The 24-month follow-up will be completed in February 2025. Conclusions The findings from the CAUSE trial will provide novel scientific understanding of the potential benefits of exercise training in long-term breast cancer survivors. Trial Registration ClinicalTrials.gov NCT04307407; https://clinicaltrials.gov/ct2/show/NCT04307407 International Registered Report Identifier (IRRID) DERR1-10.2196/45244

• Sexton, Casey; Godwin, Joshua; Ruple, Bradley; Mcintosh, Mason; Osburn, Shelby C & Hollingsworth, Blake [Vis alle 16 forfattere av denne artikkelen] (2022). Global DNA Methylation Status in Relation to Resistance Training with High vs Low Loads to Failure. The FASEB Journal. ISSN 0892-6638. 36(S1). doi: 10.1096/fasebj.2022.36.S1.R5652. Fulltekst i vitenarkiv Vis sammendrag

  Objective: Our objective was to determine how global DNA methylation status of skeletal muscle differs with resistance training (RT) to failure in trained participants using either 80% of their estimated one-repetition maximum (Est. 1-RM) (80FAIL) or 30% of their Est. 1-RM (30FAIL). Hypotheses: We hypothesize there will be a significant decrease in global DNA methylation with both RT conditions, but that 30FAIL RT will elicit a greater magnitude of hypomethylation than 80FAIL RT. Methods: Previously trained college-aged males (n= 11, age 23 ± 4 years, percent fat 11.4 ± 6.4%, training experience 4 ± 3 years, squat strength relative to body weight 1.7 ± 0.3) voluntarily underwent two bouts of RT. Participants completed both the 80FAIL and 30FAIL conditions (separated by one week). For each bout of RT, participants completed 4 sets of back squats and 4 sets leg extensions with either the 80FAIL or 30FAIL training conditions. Muscle biopsies were collected from the vastus lateralis before (PRE), 3 hours (3hPOST), and 6 hours (6hrPOST) after each RT bout. DNA was then batch-isolated from muscle tissue and submitted for analysis using the Illumina MethylationEPIC array. Results: Total number of repetitions performed were significantly higher for 30FAIL training vs 80FAIL training (p< .001), however total training volume (sets x reps x load) was not significantly different between conditions (p= 0.571). Global methylation changes between PRE, 3hPOST, and 6hPOST are presented herein. In addition, significant differences between conditions are emphasized for each post-exercise time point. Conclusions: With this study we expand our understanding of how the manipulation of RT variables affect epigenetic modifications in skeletal muscle.

• Martin, Neil R.W. & Sharples, Adam (2022). Satellite cells and exercise. I Sharples, Adam; Morton, James P & Wackerhage, Henning (Red.), Molecular Exercise Physiology: An Introduction (Second Edition). Routledge. ISSN 9781315110752. s. 314–331. doi: 10.4324/9781315110752-13. Fulltekst i vitenarkiv Vis sammendrag

  Satellite cells are skeletal muscle stem cells, which lie in a dormant state on the periphery of muscle fibres, wedged between the basal lamina and the sarcolemma, and are important in the regeneration and growth of a muscle following trauma or injury. In this chapter, the fundamental biology of satellite cells is described, along with a detailed discussion on the effects of exercise on satellite cell behaviour. The chapter also deals with contentious and contemporary issues such as the importance of satellite cells for muscle hypertrophy following loading/exercise, and how satellite cells communicate with other cell types within muscle tissue. Finally, the chapter provides a perspective on how satellite cell biology alters with ageing, and the role that exercise can play in improving satellite cell function in aged muscle tissue.

• Sharples, Adam; Turner, Daniel; Roth, Stephen; Seaborne, Robert A.; Egan, Brendan & Viggars, Mark [Vis alle 11 forfattere av denne artikkelen] (2022). Methods in molecular exercise physiology. I Sharples, Adam; Morton, James P & Wackerhage, Henning (Red.), Molecular Exercise Physiology: An Introduction (Second Edition). Routledge. ISSN 9781315110752. s. 19–60. doi: 10.4324/9781315110752-2. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Sharples, Adam & Wackerhage, Henning (2022). Introduction to molecular exercise physiology. I Sharples, Adam; Morton, James P & Wackerhage, Henning (Red.), Molecular Exercise Physiology: An Introduction (Second Edition). Routledge. ISSN 9781315110752. s. 1–17. doi: 10.4324/9781315110752-1. Fulltekst i vitenarkiv Vis sammendrag

  In this chapter, we define molecular exercise physiology and provide a history of the evolution of molecular exercise physiology as a scientific discipline. We describe how the origins of molecular exercise physiology emerged from early pioneering research undertaken by exercise biochemists and rapid advances in molecular biology techniques. The chapter includes a narrative from Professor Frank Booth, who was one of the first researchers to apply molecular biology techniques to exercise physiology, as well a narrative from exercise genomics pioneer, Professor Claude Bouchard. In this chapter, we also outline the importance of various experimental models that have enabled important discoveries in human molecular exercise physiology. We also highlight some of the landmark research contributing to this discipline. Finally, we discuss the advancement in integrative ‘OMICs’ and how this type of ‘discovery’ analyses, coupled with experimental models to confirm these discoveries, are likely to advance molecular exercise physiology as a field into the future. Finally, we provide a fundamental overview of the chapter structure for the rest of the book.

• Egan, Brendan & Sharples, Adam (2022). Signal transduction and exercise. I Sharples, Adam; Morton, James P & Wackerhage, Henning (Red.), Molecular Exercise Physiology: An Introduction (Second Edition). Routledge. ISSN 9781315110752. s. 152–189. doi: 10.4324/9781315110752-7. Fulltekst i vitenarkiv Vis sammendrag

  Adaptation to exercise is a consequence of the training stimulus, which is largely determined by the volume (as a function of frequency, intensity and duration of sessions), the type(s) (e.g. aerobic, resistance, interval and sprint) and mode(s) (e.g. running, cycling and rowing) of training performed. This chapter explores how and why skeletal muscle adapts to exercise, and how do both similar and differing adaptations to divergent types of exercise occur. We describe how molecular responses to exercise and associated exercise-induced signal transduction lead to adaptation in skeletal muscle. In this model, the exercise ‘stimulus’ generates molecular ‘signals’ that are sensed by ‘sensor’ proteins, computed and conveyed by ‘signal transduction’ proteins after which downstream ‘effector’ proteins, in turn, regulate transcription, translation or protein synthesis, protein degradation and other cellular processes. The key proteins and processes in the regulators of adaptation in skeletal muscle to exercise are described, as well as discussion of the emerging techniques to identify novel molecular regulation. Importantly, while molecular responses do exhibit some specificity in response to divergent exercise types, at present, these responses do not fully explain the divergent adaptive responses to exercise training. Lastly, the practical significance and translational potential of these investigations are described, including the concept of exercise mimetics as an illustrative example.

• Turner, Daniel; Seaborne, Robert A. & Sharples, Adam (2022). Epigenetics of exercise. I Sharples, Adam; Morton, James P & Wackerhage, Henning (Red.), Molecular Exercise Physiology: An Introduction (Second Edition). Routledge. ISSN 9781315110752. s. 122–151. doi: 10.4324/9781315110752-6. Fulltekst i vitenarkiv Vis sammendrag

  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 (2022). Studie om musklenes minne vekker oppsikt. Magne Lund-Hansen (31) «lekte» skadet for å gi forskerne nye svar. [Internet]. Bergens Tidende. Fulltekst i vitenarkiv
• Sharples, Adam (2022). Musklene kan huske tidligere trening. [Journal]. Aftenposten. Fulltekst i vitenarkiv
• Seaborne, Robert A.; Strauss, Juliette A.; Cocks, Matt; Shepherd, Sam O.; O'brien, Thomas D. & Someren, Ken A. van [Vis alle 11 forfattere av denne artikkelen] (2019). Researchers make gains in understanding epigenetic muscle memory. Scientific Reports. Video Abstract. doi: 10.21203/rs.2.17320/v1. Fulltekst i vitenarkiv
• Seaborne, Robert A.; Viggars, Mark & Sharples, Adam (2019). Commentaries on Viewpoint: "Muscle memory" not mediated by myonuclear number? Secondary analysis of human detraining data. Journal of applied physiology. ISSN 8750-7587. 127(6), s. 1819–1820. doi: 10.1152/japplphysiol.00754.2019. Fulltekst i vitenarkiv
• Turner, Daniel C.; Seaborne, Robert A.; Stewart, Claire; Murphy, Mark; Jarvis, Jonathan C. & Martin, Neil R.W. [Vis alle 7 forfattere av denne artikkelen] (2018). Mechanical loading of murine bioengineered skeletal muscle mimics the transcriptional and epigenetic response of human skeletal muscle after exercise. European Cells and Materials. eCM Online Periodical, 2018, Collection 4, s. 031–031. Fulltekst i vitenarkiv
• Sharples, Adam (2017). Cellular & Molecular Exercise Physiology: A Historical Perspective for Discovery of Mechanisms Contributing to Muscle Adaptation. Cellular and Molecular Exercise Physiology. ISSN 2049-419X. 5(1), s. e10–e10. Fulltekst i vitenarkiv
• Sharples, Adam (2016). Vitamin D & Skeletal Muscle Regeneration: A Systems Approach. Journal of Sports Medicine and Physical Fitness. ISSN 0022-4707. 65, s. 157–157. doi: 10.7600/jspfsm.65.157. Fulltekst i vitenarkiv
• Sharples, Adam (2015). Comments on the CrossTalk proposal and opposing view: The dominant mechanism causing disuse muscle atrophy is decreased protein synthesis/proteolysis. Journal of Physiology. ISSN 0022-3751. 592(24), s. 5341–5343. Fulltekst i vitenarkiv
• Sharples, Adam (2015). The role of SIRT1 in aged and glucose restricted skeletal muscle cells. Proceedings of the Physiological Society. ISSN 1749-6187. 33, s. PC25–PC25. Fulltekst i vitenarkiv
• Sharples, Adam (2015). Nucleotide supplementation does not improve repeated sprint performance. Journal of Sports Sciences. ISSN 0264-0414. 33, s. s6–s6. doi: 10.1080/02640414.2015.1110312. Fulltekst i vitenarkiv
• Sharples, Adam (2015). Skeletal muscle myoblasts have a ‘memory’ of previous TNF-α insults: Role of DNA methylation. Proceedings of the Physiological Society. ISSN 1749-6187. 33, s. PC23–PC23. Fulltekst i vitenarkiv
• Sharples, Adam (2013). Combined Effect of Hyperhydration & Pre-Cooling on Endurance Cycling Performance in Hot and Humid Conditions. Medicine & Science in Sports & Exercise. ISSN 0195-9131. 5S, s. 61–71. Fulltekst i vitenarkiv
• Sharples, Adam (2012). The effects of testosterone on molecular markers of hypertrophy in C2C12 skeletal muscle cells. Proceedings of the Physiological Society. ISSN 1749-6187. 26, s. PC61–PC61. Fulltekst i vitenarkiv
• Sharples, Adam (2011). Mechanical stimulation of 3D Bio-Engineered Skeletal Muscle. European Cells and Materials. 22(1), s. 38–38. Fulltekst i vitenarkiv
• Sharples, Adam (2011). A Putative Model of Endurance Exercise Using Bio-Engineered Skeletal Muscle. Proceedings of the Physiological Society. ISSN 1749-6187. 23, s. PC333–PC333. Fulltekst i vitenarkiv
• Sharples, Adam (2011). Artificially Aged Skeletal Myoblasts Display Reduced Regeneration in Bio-engineered Skeletal Muscle. Proceedings of the Physiological Society. ISSN 1749-6187. 23, s. PC327–PC327. Fulltekst i vitenarkiv
• Sharples, Adam (2011). Replicative ageing of myoblasts in 3-D tissue engineered collagen constructs. European Cells and Materials. 22(1), s. 39–39. Fulltekst i vitenarkiv
• Sharples, Adam (2010). Differential responses of C2 and C2C12 mouse skeletal myoblasts in the absence or presence of tumour necrosis factor- alpha (TNF-α). Endocrine Abstracts. ISSN 1479-6848. 21, s. P127–P127. Fulltekst i vitenarkiv

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