bims-musmir Biomed News
on microRNAs in muscle
Issue of 2024‒09‒22
twelve papers selected by
Katarzyna Agnieszka Goljanek-Whysall, University of Galway
  1. Temporal expression of mitochondrial life cycle markers during acute and chronic overload of rat plantaris muscles.
  2. Dysregulated FOXO1 activity drives skeletal muscle intrinsic dysfunction in amyotrophic lateral sclerosis.
  3. Mesenchymal Stromal Cell Transplantation Ameliorates Fibrosis and microRNA Dysregulation in Skeletal Muscle Ischaemia.
  4. Effect of Lactational Low-Protein Diet on Skeletal Muscle during Adulthood and Ageing in Male and Female Mouse Offspring.
  5. N-acetylaspartate promotes glycolytic-to-oxidative fiber-type switch and resistance to atrophic stimuli in myotubes.
  6. Resistance exercise in early-stage ALS patients, ALSFRS-R, Sickness Impact Profile ALS-19, and muscle transcriptome: a pilot study.
  7. Exercise training and changes in skeletal muscle mitochondrial proteins: from blots to "omics".
  8. CRISPR-Cas13d targeting suppresses repeat-associated non-AUG translation of C9orf72 hexanucleotide repeat RNA.
  9. Anabolic deficits and divergent unfolded protein response underlie skeletal and cardiac muscle growth impairments in the Yoshida hepatoma tumor model of cancer cachexia.
  10. Ameliorated cellular hallmarks of myotonic dystrophy in hybrid myotubes from patient and unaffected donor cells.
  11. Urolithin a Improves Motor Dysfunction Induced by Copper Exposure in SOD1G93A Transgenic Mice Via Activation of Mitophagy.
  12. Assessing muscle protein synthesis rates in vivo in humans: the deuterated water (2H2O) method.
  1. Front Physiol. 2024 ;15 1420276
    Temporal expression of mitochondrial life cycle markers during acute and chronic overload of rat plantaris muscles.
    Jon-Philippe K Hyatt, Emilie J Lu, Gary E McCall.
      Skeletal muscle hypertrophy is generally associated with a fast-to-slow phenotypic adaptation in both human and rodent models. Paradoxically, this phenotypic shift is not paralleled by a concomitant increase in mitochondrial content and aerobic markers that would be expected to accompany a slow muscle phenotype. To understand the temporal response of the mitochondrial life cycle (i.e., biogenesis, oxidative phosphorylation, fission/fusion, and mitophagy/autophagy) to hypertrophic stimuli, in this study, we used the functional overload (FO) model in adult female rats and examined the plantaris muscle responses at 1 and 10 weeks. As expected, the absolute plantaris muscle mass increased by ∼12 and 26% at 1 and 10 weeks following the FO procedure, respectively. Myosin heavy-chain isoform types I and IIa significantly increased by 116% and 17%, respectively, in 10-week FO plantaris muscles. Although there was a general increase in protein markers associated with mitochondrial biogenesis in acute FO muscles, this response was unexpectedly sustained under 10-week FO conditions after muscle hypertrophy begins to plateau. Furthermore, the early increase in mito/autophagy markers observed under acute FO conditions was normalized by 10 weeks, suggesting a cellular environment favoring mitochondrial biogenesis to accommodate the aerobic demands of the plantaris muscle. We also observed a significant increase in the expression of mitochondrial-, but not nuclear-, encoded oxidative phosphorylation (OXPHOS) proteins and peptides (i.e., humanin and MOTS-c) under chronic, but not acute, FO conditions. Taken together, the temporal response of markers related to the mitochondrial life cycle indicates a pattern of promoting biogenesis and mitochondrial protein expression to support the energy demands and/or enhanced neural recruitment of chronically overloaded skeletal muscle.
    Keywords:  MOTS-c; autophagy; biogenesis; mitophagy; myosin heavy chain; oxidative phosphorylation
    DOI:  https://doi.org/10.3389/fphys.2024.1420276
  2. Acta Neuropathol. 2024 Sep 16. 148(1): 43
    Dysregulated FOXO1 activity drives skeletal muscle intrinsic dysfunction in amyotrophic lateral sclerosis.
    Mónica Zufiría, Oihane Pikatza-Menoio, Maddi Garciandia-Arcelus, Xabier Bengoetxea, Andrés Jiménez, Amaia Elicegui, María Levchuk, Olatz Arnold-García, Jon Ondaro, Pablo Iruzubieta, Laura Rodríguez-Gómez, Uxoa Fernández-Pelayo, Mikel Muñoz-Oreja, Ana Aiastui, José Manuel García-Verdugo, Vicente Herranz-Pérez, Miren Zulaica, Juan José Poza, Rebeca Ruiz-Onandi, Roberto Fernández-Torrón, Juan Bautista Espinal, Mario Bonilla, Ana Lersundi, Gorka Fernández-Eulate, Javier Riancho, Ainara Vallejo-Illarramendi, Ian James Holt, Amets Sáenz, Edoardo Malfatti, Stéphanie Duguez, Lorea Blázquez, Adolfo López de Munain, Gorka Gerenu, Francisco Gil-Bea, Sonia Alonso-Martín.
      Amyotrophic Lateral Sclerosis (ALS) is a multisystemic neurodegenerative disorder, with accumulating evidence indicating metabolic disruptions in the skeletal muscle preceding disease symptoms, rather than them manifesting as a secondary consequence of motor neuron (MN) degeneration. Hence, energy homeostasis is deeply implicated in the complex physiopathology of ALS and skeletal muscle has emerged as a key therapeutic target. Here, we describe intrinsic abnormalities in ALS skeletal muscle, both in patient-derived muscle cells and in muscle cell lines with genetic knockdown of genes related to familial ALS, such as TARDBP (TDP-43) and FUS. We found a functional impairment of myogenesis that parallels defects of glucose oxidation in ALS muscle cells. We identified FOXO1 transcription factor as a key mediator of these metabolic and functional features in ALS muscle, via gene expression profiling and biochemical surveys in TDP-43 and FUS-silenced muscle progenitors. Strikingly, inhibition of FOXO1 mitigated the impaired myogenesis in both the genetically modified and the primary ALS myoblasts. In addition, specific in vivo conditional knockdown of TDP-43 or FUS orthologs (TBPH or caz) in Drosophila muscle precursor cells resulted in decreased innervation and profound dysfunction of motor nerve terminals and neuromuscular synapses, accompanied by motor abnormalities and reduced lifespan. Remarkably, these phenotypes were partially corrected by foxo inhibition, bolstering the potential pharmacological management of muscle intrinsic abnormalities associated with ALS. The findings demonstrate an intrinsic muscle dysfunction in ALS, which can be modulated by targeting FOXO factors, paving the way for novel therapeutic approaches that focus on the skeletal muscle as complementary target tissue.
    Keywords:  Amyotrophic lateral sclerosis; FOXO1; FUS; Glycolysis; Myogenesis; TDP-43
    DOI:  https://doi.org/10.1007/s00401-024-02794-y
  3. Stem Cells. 2024 Sep 16. pii: sxae058. [Epub ahead of print]
    Mesenchymal Stromal Cell Transplantation Ameliorates Fibrosis and microRNA Dysregulation in Skeletal Muscle Ischaemia.
    Clara Sanz-Nogués, Alan J Keane, Michael Creane, Sean O Hynes, Xizhe Chen, Caomhán J Lyons, Emma Horan, Stephen J Elliman, Katarzyna Goljanek-Whysall, Timothy O'Brien.
      Peripheral arterial disease (PAD) is associated with lower-extremity muscle wasting. Hallmark features of PAD-associated skeletal muscle pathology include loss of skeletal muscle mass, reduced strength and physical performance, increased inflammation, fibrosis, and adipocyte infiltration. At the molecular level, skeletal muscle ischaemia has also been associated with gene and microRNA (miRNA) dysregulation. Mesenchymal stromal cells (MSCs) have been shown to enhance muscle regeneration and improve muscle function in various skeletal muscle injuries. This study aimed to evaluate the effects of intramuscularly delivered human umbilical cord-derived MSCs (hUC-MSCs) on skeletal muscle ischaemia. Herein, we report an hUC-MSC-mediated amelioration of ischaemia-induced skeletal muscle atrophy and function via enhancement of myofibre regeneration, reduction of tissue inflammation, adipocyte accumulation, and tissue fibrosis. These changes were observed in the absence of cell-mediated enhancement of blood flow recovery as measured by Laser Doppler imaging. Furthermore, reduced tissue fibrosis in the hUC-MSC-treated group was associated with upregulation of miR-1, miR-133a, and miR-29b and downregulation of targeted pro-fibrotic genes such as Col1a1 and Fn1. Our results support the use of hUC-MSCs as a novel approach to reduce fibrosis and promote skeletal muscle regeneration after ischaemic injury in patients with PAD.
    Keywords:  fibrosis; mesenchymal stromal cells; microRNAs; muscle ischaemia; peripheral arterial disease
    DOI:  https://doi.org/10.1093/stmcls/sxae058
  4. Nutrients. 2024 Sep 01. pii: 2926. [Epub ahead of print]16(17):
    Effect of Lactational Low-Protein Diet on Skeletal Muscle during Adulthood and Ageing in Male and Female Mouse Offspring.
    Moussira Alameddine, Atilla Emre Altinpinar, Ufuk Ersoy, Ioannis Kanakis, Ioanna Myrtziou, Susan E Ozanne, Katarzyna Goljanek-Whysall, Aphrodite Vasilaki.
      Sarcopenia is characterised by the loss of skeletal muscle mass and function, which leads to a high risk of increased morbidity and mortality. Maternal malnutrition has been linked to impaired development of skeletal muscle of the offspring; however, there are limited studies that report the long-term effect of a maternal low-protein diet during lactation on the ageing of skeletal muscles. This study aimed to examine how a maternal low-protein diet (LPD) during lactation affects skeletal muscle ageing in the offspring. Pups born from control mothers were lactated by mothers fed with an LPD. Post-weaning, mice were either maintained on an LPD or switched to a control, normal-protein diet (NPD). In males, an LPD mainly affected the size of the myofibres without a major effect on fibre number and led to reduced grip strength in ageing mice (24 months). Female mice from mothers on an LPD had a lower body and muscle weight at weaning but caught up with control mice at 3 months. During ageing, the muscle weight, myofibre number and survival rate of female pups were significantly affected. These findings highlight the effect of an LPD during lactation on skeletal muscle ageing, the lifespan of offspring and the importance of sexual dimorphism in response to dietary challenges.
    Keywords:  ageing; lactation; low-protein diet (LPD); sarcopenia; skeletal muscle
    DOI:  https://doi.org/10.3390/nu16172926
  5. Cell Death Dis. 2024 Sep 19. 15(9): 686
    N-acetylaspartate promotes glycolytic-to-oxidative fiber-type switch and resistance to atrophic stimuli in myotubes.
    Serena Castelli, Enrico Desideri, Leonardo Laureti, Federica Felice, Angela De Cristofaro, Silvia Scaricamazza, Giacomo Lazzarino, Maria Rosa Ciriolo, Fabio Ciccarone.
      N-acetylaspartate (NAA) is a neuronal metabolite that can be extruded in extracellular fluids and whose blood concentration increases in several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Aspartoacylase (ASPA) is the enzyme responsible for NAA breakdown. It is abundantly expressed in skeletal muscle and most other human tissues, but the role of NAA catabolism in the periphery is largely neglected. Here we demonstrate that NAA treatment of differentiated C2C12 muscle cells increases lipid turnover, mitochondrial biogenesis and oxidative metabolism at the expense of glycolysis. These effects were ascribed to NAA catabolism, as CRISPR/Cas9 ASPA KO cells are insensitive to NAA administration. Moreover, the metabolic switch induced by NAA was associated with an augmented resistance to atrophic stimuli. Consistently with in vitro results, SOD1-G93A ALS mice show an increase in ASPA levels in those muscles undergoing the glycolytic to oxidative switch during the disease course. The impact of NAA on the metabolism and resistance capability of myotubes supports a role for this metabolite in the phenotypical adaptations of skeletal muscle in neuromuscular disorders.
    DOI:  https://doi.org/10.1038/s41419-024-07047-0
  6. Sci Rep. 2024 09 17. 14(1): 21729
    Resistance exercise in early-stage ALS patients, ALSFRS-R, Sickness Impact Profile ALS-19, and muscle transcriptome: a pilot study.
    Omar Jawdat, Jason Rucker, Tomoki Nakano, Kotaro Takeno, Jeffery Statland, Mamatha Pasnoor, Mazen M Dimachkie, Carla Sabus, Yomna Badawi, Suzanne L Hunt, Naoko H Tomioka, Sumedha Gunewardena, Clark Bloomer, Heather M Wilkins, Laura Herbelin, Richard J Barohn, Hiroshi Nishimune.
      Amyotrophic lateral sclerosis (ALS) patients lack effective treatments to maintain motor and neuromuscular function. This study aimed to evaluate the effect of a home-based exercise program on muscle strength, ALS scores, and transcriptome in ALS patients, Clinical Trials.gov #NCT03201991 (28/06/2017). An open-label, non-randomized pilot clinical trial was conducted in seven individuals with early-stage ALS. Participants were given 3 months of home-based resistance exercise focusing on the quadriceps muscles. The strength of exercised muscle was evaluated using bilateral quadriceps strength with manual muscle testing, handheld dynamometers, five times sit-to-stand, and Timed-Up-and-Go before and after the exercise program. In addition, changes in the Sickness Impact Profile ALS-19 (SIP/ALS-19) as the functional outcome measure and the transcriptome of exercised muscles were compared before and after the exercise. The primary outcome of muscle strength did not change significantly by the exercise program. The exercise program maintained the SIP/ALS-19 and the ALS Functional Rating Scale-Revised (ALSFRS-R). Transcriptome analysis revealed that exercise reverted the expression level of genes decreased in ALS, including parvalbumin. Three months of moderately intense strength and conditioning exercise maintained muscle strength of the exercised muscle and ALSFRS-R scores and had a positive effect on patients' muscle transcriptome.
    Keywords:  Amyotrophic lateral sclerosis; Clinical trial; Exercise
    DOI:  https://doi.org/10.1038/s41598-024-72355-6
  7. Crit Rev Biochem Mol Biol. 2024 Sep 17. 1-23
    Exercise training and changes in skeletal muscle mitochondrial proteins: from blots to "omics".
    Elizabeth G Reisman, Nikeisha J Caruana, David J Bishop.
      Mitochondria are essential, membrane-enclosed organelles that consist of ∼1100 different proteins, which allow for many diverse functions critical to maintaining metabolism. Highly metabolic tissues, such as skeletal muscle, have a high mitochondrial content that increases with exercise training. The classic western blot technique has revealed training-induced increases in the relatively small number of individual mitochondrial proteins studied (∼5% of the >1100 proteins in MitoCarta), with some of these changes dependent on the training stimulus. Proteomic approaches have identified hundreds of additional mitochondrial proteins that respond to exercise training. There is, however, surprisingly little crossover in the mitochondrial proteins identified in the published human training studies. This suggests that to better understand the link between training-induced changes in mitochondrial proteins and metabolism, future studies need to move beyond maximizing protein detection to adopting methods that will increase the reliability of the changes in protein abundance observed.
    Keywords:  Mitochondria; fiber type; proteins; proteomics; skeletal muscle; training
    DOI:  https://doi.org/10.1080/10409238.2024.2383408
  8. J Clin Invest. 2024 Sep 17. pii: e179016. [Epub ahead of print]
    CRISPR-Cas13d targeting suppresses repeat-associated non-AUG translation of C9orf72 hexanucleotide repeat RNA.
    Honghe Liu, Xiao-Feng Zhao, Yu-Ning Lu, Lindsey R Hayes, Jiou Wang.
      A hexanucleotide GGGGCC repeat expansion in the non-coding region of C9orf72 gene is the most common genetic mutation identified in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The resulting repeat RNA and dipeptide repeat proteins from non-conventional repeat translation have been recognized as important markers associated with the diseases. CRISPR-Cas13d, a powerful RNA targeting tool, has faced challenges in effectively targeting RNA with stable secondary structures. Here we report that CRISPR-Cas13d can be optimized to specifically target GGGGCC repeat RNA. Our results demonstrate that the CRISPR-Cas13d system can be harnessed to significantly diminish the translation of poly-dipeptides originating from the GGGGCC repeat RNA. This efficacy has been validated in various cell types, including induced pluripotent stem cells and differentiated motor neurons originating from C9orf72-ALS patients, as well as in C9orf72 repeat transgenic mice. These findings demonstrate the application of CRISPR-Cas13d in targeting RNA with intricate higher-order structures and suggest a potential therapeutic approach for ALS and FTD.
    Keywords:  Gene therapy; Genetics; Molecular biology; Neurodegeneration; Neuroscience
    DOI:  https://doi.org/10.1172/JCI179016
  9. Physiol Rep. 2024 Sep;12(18): e70044
    Anabolic deficits and divergent unfolded protein response underlie skeletal and cardiac muscle growth impairments in the Yoshida hepatoma tumor model of cancer cachexia.
    Daniel J Belcher, Nina Kim, Blanca Navarro-Llinas, Maria Möller, Francisco J López-Soriano, Silvia Busquets, Gustavo A Nader.
      Cancer cachexia manifests as whole body wasting, however, the precise mechanisms governing the alterations in skeletal muscle and cardiac anabolism have yet to be fully elucidated. In this study, we explored changes in anabolic processes in both skeletal and cardiac muscles in the Yoshida AH-130 ascites hepatoma model of cancer cachexia. AH-130 tumor-bearing rats experienced significant losses in body weight, skeletal muscle, and heart mass. Skeletal and cardiac muscle loss was associated with decreased ribosomal (r)RNA, and hypophosphorylation of the eukaryotic factor 4E binding protein 1. Endoplasmic reticulum stress was evident by higher activating transcription factor mRNA in skeletal muscle and growth arrest and DNA damage-inducible protein (GADD)34 mRNA in both skeletal and cardiac muscles. Tumors provoked an increase in tissue expression of interferon-γ in the heart, while an increase in interleukin-1β mRNA was apparent in both skeletal and cardiac muscles. We conclude that compromised skeletal muscle and heart mass in the Yoshida AH-130 ascites hepatoma model involves a marked reduction translational capacity and efficiency. Furthermore, our observations suggest that endoplasmic reticulum stress and tissue production of pro-inflammatory factors may play a role in the development of skeletal and cardiac muscle wasting.
    Keywords:  cancer; inflammation; ribosomal RNA; unfolded protein response; wasting
    DOI:  https://doi.org/10.14814/phy2.70044
  10. Stem Cell Res Ther. 2024 Sep 15. 15(1): 302
    Ameliorated cellular hallmarks of myotonic dystrophy in hybrid myotubes from patient and unaffected donor cells.
    Renée H L Raaijmakers, C Rosanne M Ausems, Marieke Willemse, Sarah A Cumming, Baziel G M van Engelen, Darren G Monckton, Hans van Bokhoven, Derick G Wansink.
      BACKGROUND: Cell-based strategies are being explored as a therapeutic option for muscular dystrophies, using a variety of cell types from different origin and with different characteristics. Primary pericytes are multifunctional cells found in the capillary bed that exhibit stem cell-like and myogenic regenerative properties. This unique combination allows them to be applied systemically, presenting a promising opportunity for body-wide muscle regeneration. We previously reported the successful isolation of ALP+ pericytes from skeletal muscle of patients with myotonic dystrophy type 1 (DM1). These pericytes maintained normal growth parameters and myogenic characteristics in vitro despite the presence of nuclear (CUG)n RNA foci, the cellular hallmark of DM1. Here, we examined the behaviour of DM1 pericytes during myogenic differentiation.METHODS: DMPK (CTG)n repeat lengths in patient pericytes were assessed using small pool PCR, to be able to relate variation in myogenic properties and disease hallmarks to repeat expansion. Pericytes from unaffected controls and DM1 patients were cultured under differentiating conditions in vitro. In addition, the pericytes were grown in co-cultures with myoblasts to examine their regenerative capacity by forming hybrid myotubes. Finally, the effect of pericyte fusion on DM1 disease hallmarks was investigated.
    RESULTS: Small pool PCR analysis revealed the presence of somatic mosaicism in pericyte cell pools. Upon differentiation to myotubes, DMPK expression was upregulated, leading to an increase in nuclear foci sequestering MBNL1 protein. Remarkably, despite the manifestation of these disease biomarkers, patient-derived pericytes demonstrated myogenic potential in co-culture experiments comparable to unaffected pericytes and myoblasts. However, only the unaffected pericytes improved the disease hallmarks in hybrid myotubes. From 20% onwards, the fraction of unaffected nuclei in myotubes positively correlated with a reduction of the number of RNA foci and an increase in the amount of free MBNL1.
    CONCLUSIONS: Fusion of only a limited number of unaffected myogenic precursors to DM1 myotubes already ameliorates cellular disease hallmarks, offering promise for the development of cell transplantation strategies to lower disease burden.
    DOI:  https://doi.org/10.1186/s13287-024-03913-y
  11. Mol Neurobiol. 2024 Sep 18.
    Urolithin a Improves Motor Dysfunction Induced by Copper Exposure in SOD1G93A Transgenic Mice Via Activation of Mitophagy.
    Huan Zhang, Chuanyue Gao, Deguang Yang, Lulin Nie, Kaiwu He, Chongyang Chen, Shangming Li, Guanqin Huang, Li Zhou, Xinfeng Huang, Desheng Wu, Jianjun Liu, Zhenlie Huang, Jie Wang, Weihua Li, Zhaohui Zhang, Xifei Yang, Liangyu Zou.
      Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease pathologically characterized by selective degeneration of motor neurons resulting in a catastrophic loss of motor function. The present study aimed to investigate the effect of copper (Cu) exposure on progression of ALS and explore the therapeutic effect and mechanism of Urolithin A (UA) on ALS. 0.13 PPM copper chloride drinking water was administrated in SOD1G93A transgenic mice at 6 weeks, UA at a dosage of 50 mg/kg/day was given for 6 weeks after a 7-week Cu exposure. Motor ability was assessed before terminal anesthesia. Muscle atrophy and fibrosis, motor neurons, astrocytes and microglia in the spinal cord were evaluated by H&E, Masson, Sirius Red, Nissl and Immunohistochemistry Staining. Proteomics analysis, Western blotting and ELISA were conducted to detect protein expression. Mitochondrial adenosine triphosphate (ATP) and malondialdehyde (MDA) levels were measured using an assay kit. Cu-exposure worsened motor function, promoted muscle fibrosis, loss of motor neurons, and astrocyte and microglial activation. It also induced abnormal changes in mitochondria-related biological processes, leading to a significant reduction in ATP levels and an increase in MDA levels. Upregulation of P62 and downregulation of Parkin, PINK1, and LAMP1 were revealed in SOD1G93A mice with Cu exposure. Administration of UA activated mitophagy, modulated mitochondria dysfunction, reduced neuroinflammation, and improved gastrocnemius muscle atrophy and motor dysfunction in SOD1G93A mice with Cu exposure. Mitophagy plays critical role in ALS exacerbated by Cu exposure. UA administration may be a promising treatment strategy for ALS.
    Keywords:  Amyotrophic lateral sclerosis; Copper; Mitophagy; Motor dysfunction; Urolithin A
    DOI:  https://doi.org/10.1007/s12035-024-04473-1
  12. J Nutr. 2024 Sep 13. pii: S0022-3166(24)01029-0. [Epub ahead of print]
    Assessing muscle protein synthesis rates in vivo in humans: the deuterated water (2H2O) method.
    Andrew M Holwerda, Philip J Atherton, Kenneth Smith, Daniel J Wilkinson, Stuart M Phillips, Luc J C van Loon.
      Skeletal muscle tissue is in a constant state of turnover, with muscle tissue protein synthesis and breakdown rates ranging between 1-2 % across the day in vivo in humans. Muscle tissue remodeling is largely controlled by the up- and down-regulation of muscle tissue protein synthesis rates. Research studies generally apply stable isotope labeled amino acids to assess muscle protein synthesis rates in vivo in humans. Following labeled amino acid administration in a laboratory setting, muscle tissue samples are collected over several hours to assess the incorporation rate of these labeled amino acids in muscle tissue protein. To allow quantification of bulk muscle protein synthesis rates over more prolonged periods, the use of deuterated water methodology has regained much interest. Ingestion of daily boluses of deuterium oxide (2H2O) results in 2H-enrichment of the body water pool. The available 2H-atoms become incorporated into endogenously synthesized alanine primarily through transamination of pyruvate in the liver. With 2H-alanine widely available to all tissues, it becomes incorporated into de novo synthesized tissue proteins. Assessing the increase in tissue protein-bound 2H-alanine enrichment in muscle biopsy samples over time allows for calculation of muscle protein synthesis rates over several days or even weeks. As the deuterated water method allows for assessment of muscle tissue protein synthesis rates under free living conditions in non-laboratory settings, there is an increasing interest in its application. This manuscript describes the theoretical background of the deuterated water method and offers a comprehensive tutorial to correctly apply the method to determine bulk muscle protein synthesis rates in vivo in humans.
    Keywords:  Aging; Dietary Protein; Exercise; Muscle Atrophy; Muscle hypertrophy
    DOI:  https://doi.org/10.1016/j.tjnut.2024.09.012
This page is being maintained by Thomas Krichel. It was last updated on 2024‒09‒22 at 20:00.