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Sulfur amino acid supplementation displays therapeutic potential in a C. elegans model of Duchenne muscular dystrophy (2022)
Journal Article
Ellwood, R. A., Slade, L., Lewis, J., Torregrossa, R., Sudevan, S., Piasecki, M., …Szewczyk, N. J. (2022). Sulfur amino acid supplementation displays therapeutic potential in a C. elegans model of Duchenne muscular dystrophy. Communications Biology, 5(1), Article 1255. https://doi.org/10.1038/s42003-022-04212-z

Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD), a common muscle disease that manifests with muscle weakness, wasting, and degeneration. An emerging theme in DMD pathophysiology is an intramuscular deficit in the gasotransmit... Read More about Sulfur amino acid supplementation displays therapeutic potential in a C. elegans model of Duchenne muscular dystrophy.

Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization (2022)
Journal Article
Shur, N. F., Simpson, E. J., Crossland, H., Chivaka, P. K., Constantin, D., Cordon, S. M., …Greenhaff, P. L. (2022). Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization. Journal of Cachexia, Sarcopenia and Muscle, 13(6), 2999-3013. https://doi.org/10.1002/jcsm.13075

Background: Bed rest (BR) reduces whole-body insulin-stimulated glucose disposal (GD) and alters muscle fuel metabolism, but little is known about metabolic adaptation from acute to chronic BR nor the mechanisms involved, particularly when volunteers... Read More about Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization.

Caenorhabditis elegans as a Model System for Duchenne Muscular Dystrophy (2021)
Journal Article
Ellwood, R. A., Piasecki, M., & Szewczyk, N. J. (2021). Caenorhabditis elegans as a Model System for Duchenne Muscular Dystrophy. International Journal of Molecular Sciences, 22(9), Article 4891. https://doi.org/10.3390/ijms22094891

The nematode worm Caenorhabditis elegans has been used extensively to enhance our understanding of the human neuromuscular disorder Duchenne Muscular Dystrophy (DMD). With new arising clinically relevant models, technologies and treatments, there is... Read More about Caenorhabditis elegans as a Model System for Duchenne Muscular Dystrophy.

Mitochondrial hydrogen sulfide supplementation improves health in the C. elegans Duchenne muscular dystrophy model (2021)
Journal Article
Ellwood, R. A., Hewitt, J. E., Torregrossa, R., Philp, A. M., Hardee, J. P., Hughes, S., …Szewczyk, N. J. (2021). Mitochondrial hydrogen sulfide supplementation improves health in the C. elegans Duchenne muscular dystrophy model. Proceedings of the National Academy of Sciences, 118(9), Article e2018342118. https://doi.org/10.1073/pnas.2018342118

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle degeneration and weakness due to mutations in the dystrophin gene. The symptoms of DMD share similarities with those of accelerated aging. Recentl... Read More about Mitochondrial hydrogen sulfide supplementation improves health in the C. elegans Duchenne muscular dystrophy model.

Network analysis of human muscle adaptation to aging and contraction (2020)
Journal Article
Etheridge, T., Willis, C., Atherton, P., Ames, R., Szewczyk, N., Deane, C., …Lund, J. (2020). Network analysis of human muscle adaptation to aging and contraction. Aging, 12(1), 740-755. https://doi.org/10.18632/aging.102653

Resistance exercise (RE) remains a primary approach for minimising aging muscle decline. Understanding muscle adaptation to individual contractile components of RE (eccentric, concentric) might optimise RE-based intervention strategies. Herein, we em... Read More about Network analysis of human muscle adaptation to aging and contraction.

Pluronic gel-based burrowing assay for rapid assessment of neuromuscular health in C. elegans (2019)
Journal Article
Lesanpezeshki, L., Hewitt, J. E., Laranjeiro, R., Antebi, A., Driscoll, M., Szewczyk, N. J., …Vanapalli, S. A. (2019). Pluronic gel-based burrowing assay for rapid assessment of neuromuscular health in C. elegans. Scientific Reports, 9, Article 15246. https://doi.org/10.1038/s41598-019-51608-9

Whole-organism phenotypic assays are central to the assessment of neuromuscular function and health in model organisms such as the nematode C. elegans. In this study, we report a new assay format for engaging C. elegans in burrowing that enables rapi... Read More about Pluronic gel-based burrowing assay for rapid assessment of neuromuscular health in C. elegans.

Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men (2019)
Journal Article
Gharahdaghi, N., Rudrappa, S., Brook, M. S., Idris, I., Crossland, H., Hamrock, C., …Atherton, P. J. (2019). Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men. Journal of Cachexia, Sarcopenia and Muscle, 10(6), 1276-1294. https://doi.org/10.1002/jcsm.12472

Background: The andropause is associated with declines in serum testosterone (T), loss of muscle mass (sarcopenia) and frailty. Two major interventions purported to offset sarcopenia are anabolic steroid therapies and resistance exercise training (RE... Read More about Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men.

Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae (2019)
Journal Article
Overbey, E. G., Paul, A. M., da Silveira, W. A., Tahimic, C. G., Reinsch, S. S., Szewczyk, N., …Mao, X. W. (2019). Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae. International Journal of Molecular Sciences, 20(17), Article 4094. https://doi.org/10.3390/ijms20174094

Spaceflight poses many challenges for humans. Ground-based analogs typically focus on single parameters of spaceflight and their associated acute effects. This study assesses the long-term transcriptional effects following single and combination spac... Read More about Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae.

Mitochondrial dysfunction causes Ca2+ overload and ECM degradation–mediated muscle damage in C. elegans (2019)
Journal Article
Sudevan, S., Takiura, M., Kubota, Y., Higashitani, N., Cooke, M., Ellwood, R. A., …Higashitani, A. (2019). Mitochondrial dysfunction causes Ca2+ overload and ECM degradation–mediated muscle damage in C. elegans. FASEB Journal, 33(8), 9540-9550. https://doi.org/10.1096/fj.201802298r

Mitochondrial dysfunction impairs muscle health and causes subsequent muscle wasting. This study explores the role of mitochondrial dysfunction as an intramuscular signal for the extracellular matrix (ECM)–based proteolysis and, consequentially, musc... Read More about Mitochondrial dysfunction causes Ca2+ overload and ECM degradation–mediated muscle damage in C. elegans.

The acute transcriptional response to resistance exercise: impact of age and contraction mode (2019)
Journal Article
Deane, C. S., Ames, R. M., Phillips, B. E., Weedon, M. N., Willis, C. R., Boereboom, C., …Etheridge, T. (2019). The acute transcriptional response to resistance exercise: impact of age and contraction mode. Aging, 11(7), 2111-2126. https://doi.org/10.18632/aging.101904

Optimization of resistance exercise (RE) remains a hotbed of research for muscle building and maintenance. However, the interactions between the contractile components of RE (i.e. concentric (CON) and eccentric (ECC)) and age, are poorly defined. We... Read More about The acute transcriptional response to resistance exercise: impact of age and contraction mode.

Worms in space for outreach on earth: space life science activities for the classroom (2018)
Journal Article
Gaffney, C. J., Pollard, A. K., Deane, C. S., Cooke, M., Balsamo, M., Hewitt, J., …Phillips, B. E. (2018). Worms in space for outreach on earth: space life science activities for the classroom. Gravitational and space research : publication of the American Society for Gravitational and Space Research, 6(2), 74-82

Long term spaceflight is associated with the loss of skeletal muscle mass and function. The Molecular Muscle Experiment (MME) seeks to identify the causes of muscle decline in space and test potential therapies to attenuate this in the microscopic wo... Read More about Worms in space for outreach on earth: space life science activities for the classroom.

Greater loss of mitochondrial function with ageing is associated with earlier onset of sarcopenia in C. elegans (2018)
Journal Article
Gaffney, C. J., Pollard, A., Barratt, T. F., Constantin-Teodosiu, D., Greenhaff, P. L., & Szewczyk, N. J. (2018). Greater loss of mitochondrial function with ageing is associated with earlier onset of sarcopenia in C. elegans. Aging, 10(11), 3382-3396. https://doi.org/10.18632/aging.101654

Sarcopenia, the age-related decline of muscle, is a significant and growing public health burden. C. elegans, a model organism for investigating the mechanisms of ageing, also displays sarcopenia, but the underlying mechanism(s) remain elusive. Here,... Read More about Greater loss of mitochondrial function with ageing is associated with earlier onset of sarcopenia in C. elegans.

Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of C. elegans and its functional response to drugs (2018)
Journal Article
Hewitt, J. E., Pollard, A. K., Lesanpezeshki, L., Deane, C. S., Gaffney, C. J., Etheridge, T., …Vanapalli, S. A. (2018). Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of C. elegans and its functional response to drugs. Disease Models and Mechanisms, 11(12), https://doi.org/10.1242/dmm.036137

Muscle strength is a key clinical parameter used to monitor the progression of human muscular dystrophies including Duchenne and Becker muscular dystrophies. Although Caenorhabditis elegans is an established genetic model for studying mechanisms and... Read More about Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of C. elegans and its functional response to drugs.

Levels of acid sphingomyelinase (ASM) in Caenorhabditis elegans in microgravity (2018)
Journal Article
Gravely, A., Vlasov, A., Freeman, A., Wu, K., Szewczyk, N. J., D'Cruz, R., & Batt, J. (2018). Levels of acid sphingomyelinase (ASM) in Caenorhabditis elegans in microgravity. Gravitational and space research : publication of the American Society for Gravitational and Space Research, 6(1), 27-36

Both Amyotrophic Lateral Sclerosis (ALS) patients and astronauts in spaceflight suffer from muscle atrophy. Previous research suggests that the enzyme acid sphingomyelinase (ASM) may be involved in the pathogenesis of ALS, but it is not known if ASM... Read More about Levels of acid sphingomyelinase (ASM) in Caenorhabditis elegans in microgravity.

NemaFlex: a microfluidics-based technology for standardized measurement of muscular strength of C. elegans (2018)
Journal Article
Rahman, M., Hewitt, J. E., Van-Bussell, F., Edwards, H., Blawzdziewicz, J., Szewczyk, N. J., …Vanapalli, S. A. (2018). NemaFlex: a microfluidics-based technology for standardized measurement of muscular strength of C. elegans. Lab on a Chip, 15, https://doi.org/10.1039/C8LC00103K

Muscle strength is a functional measure of quality of life in humans. Declines in muscle strength are manifested in diseases as well as during inactivity, aging, and space travel. With conserved muscle biology, the simple genetic model C. elegans is... Read More about NemaFlex: a microfluidics-based technology for standardized measurement of muscular strength of C. elegans.

Impact of the calcium form of ?-hydroxy-?-methylbutyrate upon human skeletal muscle protein metabolism (2017)
Journal Article
Wilkinson, D. J., Hossain, T., Limb, M. C., Phillips, B. E., Lund, J., Williams, J. P., …Atherton, P. J. (2018). Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism. Clinical Nutrition, 37(6), 2068-2075. https://doi.org/10.1016/j.clnu.2017.09.024

© 2017 The Authors Background & aims: β-hydroxy-β-methylbutyrate (HMB) is purported as a key nutritional supplement for the preservation of muscle mass in health, disease and as an ergogenic aid in exercise. Of the two available forms of HMB (calcium... Read More about Impact of the calcium form of ?-hydroxy-?-methylbutyrate upon human skeletal muscle protein metabolism.

A novel D2O tracer method to quantify RNA turnover as a biomarker of de novo ribosomal biogenesis, in vitro, in animal models, and in human skeletal muscle (2017)
Journal Article
Brook, M. S., Wilkinson, D., Mitchell, W. K., Lund, J. N., Phillips, B. E., Szewczyk, N. J., …Atherton, P. J. (2017). A novel D2O tracer method to quantify RNA turnover as a biomarker of de novo ribosomal biogenesis, in vitro, in animal models, and in human skeletal muscle. AJP - Endocrinology and Metabolism, 313(6), Article E681-E689. https://doi.org/10.1152/ajpendo.00157.2017

Current methods to quantify in vivo RNA dynamics are limited. Here, we developed a novel stable isotope (D2O) methodology to quantify RNA synthesis (i.e., ribosomal biogenesis) in cells, animal models, and humans. First, proliferating C2C12 cells wer... Read More about A novel D2O tracer method to quantify RNA turnover as a biomarker of de novo ribosomal biogenesis, in vitro, in animal models, and in human skeletal muscle.

Functional phosphatome requirement for protein homeostasis, networked mitochondria, and sarcomere structure in C. elegans muscle (2017)
Journal Article
Lehmann, S., Bass, J. J., Barratt, T. F., Ali, M. Z., & Szewczyk, N. J. (2017). Functional phosphatome requirement for protein homeostasis, networked mitochondria, and sarcomere structure in C. elegans muscle. Journal of Cachexia, Sarcopenia and Muscle, 8(4), 660-672. https://doi.org/10.1002/jcsm.12196

Background: Skeletal muscle is central to locomotion and metabolic homeostasis. The laboratory worm C. elegans has been developed into a genomic model for assessing the genes and signals that regulate muscle development and protein degradation. Past... Read More about Functional phosphatome requirement for protein homeostasis, networked mitochondria, and sarcomere structure in C. elegans muscle.

Synchronous deficits in cumulative muscle protein synthesis and ribosomal biogenesis underlie age-related anabolic resistance to exercise in humans (2016)
Journal Article
Brook, M. S., Wilkinson, D. J., Mitchell, W. K., Lund, J. N., Phillips, B. E., Szewczyk, N. J., …Atherton, P. J. (2016). Synchronous deficits in cumulative muscle protein synthesis and ribosomal biogenesis underlie age-related anabolic resistance to exercise in humans. Journal of Physiology, 594(24), 7399-7417. https://doi.org/10.1113/JP272857

Ageing is associated with impaired hypertrophic responses to resistance exercise training (RET). Here we investigated the aetiology of ‘anabolic resistance’ in older humans. Twenty healthy male individuals, 10 younger (Y; 23 ± 1 years) and 10 older (... Read More about Synchronous deficits in cumulative muscle protein synthesis and ribosomal biogenesis underlie age-related anabolic resistance to exercise in humans.