bims-moremu 2024-02-18 papers

bims-moremu

Biomed News

on Molecular regulators of muscle mass

Issue of 2024–02–18
24 papers selected by
Anna Vainshtein, Craft Science Inc.

Characterizing the effects of muscle-specific GSK3a/b reduction on murine muscle contractility and metabolism in female mice.
Myosin heavy chain-perinatal regulates skeletal muscle differentiation, oxidative phenotype and regeneration.
Effects of chronic alcohol intoxication on aerobic exercise-induced adaptations in female mice.
Comment on "Fiber-type traps: revisiting common misconceptions about skeletal muscle fiber types with application to motor control, biomechanics, physiology, and biology".
Neurofibromin 1 controls metabolic balance and Notch-dependent quiescence of murine juvenile myogenic progenitors.
Muscle eosinophilia is a hallmark of chronic disease in facioscapulohumeral muscular dystrophy.
Low-intensity pulsed ultrasound (LIPUS) promotes skeletal muscle regeneration by regulating PGC-1α/AMPK/GLUT4 pathways in satellite cells/myoblasts.
Induced degeneration and regeneration in aged muscle reduce tubular aggregates but not muscle function.
Disruption of Hepatic Mitochondrial Pyruvate and Amino Acid Metabolism Impairs Gluconeogenesis and Endurance Exercise Capacity in Mice.
Oleanolic acid alleviates obesity-induced skeletal muscle atrophy via the PI3K/Akt signaling pathway.
Cellular activation patterns of CD10+ fibro-adipogenic progenitors across acquired disease states in human skeletal muscle biopsies.
Passive exercise is an effective alternative to HRT for restoring OVX induced mitochondrial dysfunction in skeletal muscle.
Associations of accelerometry-measured and self-reported physical activity and sedentary behavior with skeletal muscle energetics: The Study of Muscle, Mobility and Aging (SOMMA).
Histological and biochemical changes in lymphatic vessels after skeletal muscle injury induced by lengthening contraction in male mice.
Lactate induces C2C12 myoblasts differentiation by mediating ROS/p38 MAPK signalling pathway.
Simulated microgravity attenuates myogenesis and contractile function of 3D engineered skeletal muscle tissues.
Associations of Skeletal Muscle Mass, Muscle Fat Infiltration, Mitochondrial Energetics, and Cardiorespiratory Fitness with Liver Fat Among Older Adults.
Role of the ubiquitin-proteasome system in the sarcopenic-like phenotype induced by CCL5/RANTES.
Biallelic variants in SNUPN cause a limb girdle muscular dystrophy with myofibrillar-like features.
Treatment of infantile-onset Pompe disease in a rat model with muscle-directed AAV gene therapy.
Culture substrate stiffness impacts human myoblast contractility-dependent proliferation and nuclear envelope wrinkling.
Decreased sarcoplasmic reticulum phospholipids in human skeletal muscle are associated with metabolic syndrome.
Dramatic genome-wide reprogramming of mRNA in hypometabolic muscle.
The 50th anniversary of the European Society for Muscle Research: a journey through half a century of scientific advances.

Am J Physiol Cell Physiol. 2024 Feb 12.

Characterizing the effects of muscle-specific GSK3a/b reduction on murine muscle contractility and metabolism in female mice.

Briana L Hockey, Michael S Finch, Jessica L Braun, Ahmad Mohammad, Lucas A Maddalena, Rene Vandenboom, Jeffrey A Stuart, Brian D Roy, Rebecca E K MacPherson, Val A Fajardo.

  Dysregulation of skeletal muscle morphology and metabolism is associated with chronic diseases such as obesity and type 2 diabetes. The enzyme glycogen synthase kinase 3 (GSK3) is highly involved in skeletal muscle physiology and metabolism, acting as a negative regulator of muscle size, strength, adaptive thermogenesis, and glucose homeostasis. Correspondingly, we have shown that partial gene expression knockdown (~40%) of gsk3 specifically in skeletal muscle increases lean mass, reduces fat mass, and activates muscle-based adaptive thermogenesis via sarco(endo)plasmic reticulum Ca2+ (SERCA) uncoupling in male mice. However, the effects of partial GSK3 knockdown in female mice have yet to be investigated. Here, we examined the effects of muscle-specific GSK3 knockdown on body composition, muscle size and strength, and whole-body metabolism in female C57BL/6J mice. Our results show that GSK3 content is higher in the female soleus vs. the male soleus; however, there were no differences in the extensor digitorum longus (EDL). Furthermore, muscle-specific GSK3 knockdown did not alter body composition in female mice, nor did it alter daily energy expenditure, glucose/insulin tolerance, mitochondrial respiration, or the expression of the SERCA uncouplers sarcolipin and neuronatin. We also did not find any differences in soleus muscle size, strength, or fatigue resistance. In the EDL, we found an increase in cross-sectional area associated with an increase in absolute force production but there were no differences in fatigability. Therefore, our study highlights sex-differences in the response to genetic reduction of gsk3, with most of the effects previously observed in male mice being absent in females.

Keywords:  Energy expenditure; Force production; Muscle; Thermogenesis

DOI:  https://doi.org/10.1152/ajpcell.00398.2023
FEBS J. 2024 Feb 15.

Myosin heavy chain-perinatal regulates skeletal muscle differentiation, oxidative phenotype and regeneration.

Akashi Sharma, Aatifa Zehra, Sam J Mathew.

  Myosin heavy chain-perinatal (MyHC-perinatal) is one of two development-specific myosin heavy chains expressed exclusively during skeletal muscle development and regeneration. The specific functions of MyHC-perinatal are unclear, although mutations are known to lead to contracture syndromes such as Trismus-pseudocamptodactyly syndrome. Here, we characterize the functions of MyHC-perinatal during skeletal muscle differentiation and regeneration. Loss of MyHC-perinatal function leads to enhanced differentiation characterized by increased expression of myogenic regulatory factors and differentiation index as well as reduced reserve cell numbers in vitro. Proteomic analysis revealed that loss of MyHC-perinatal function results in a switch from oxidative to glycolytic metabolism in myofibers, suggesting a shift from slow type I to fast type IIb fiber type, also supported by reduced mitochondrial numbers. Paracrine signals mediate the effect of loss of MyHC-perinatal function on myogenic differentiation, possibly mediated by non-apoptotic caspase-3 signaling along with enhanced levels of the pro-survival apoptosis regulator Bcl2 and nuclear factor kappa-B (NF-κB). Knockdown of MyHC-perinatal during muscle regeneration in vivo results in increased expression of the differentiation marker myogenin (MyoG) and impaired differentiation, evidenced by smaller myofibers, elevated fibrosis and reduction in the number of satellite cells. Thus, we find that MyHC-perinatal is a crucial regulator of myogenic differentiation, myofiber oxidative phenotype and regeneration.

Keywords:  Myh8; differentiation; mouse; satellite cells; skeletal muscle

DOI:  https://doi.org/10.1111/febs.17085
J Appl Physiol (1985). 2024 Feb 15.

Effects of chronic alcohol intoxication on aerobic exercise-induced adaptations in female mice.

Abigail L Tice, Bradley S Gordon, Emma Fletcher, Addison G McNeill, Grant R Laskin, Joseph A Laudato, Michael L Rossetti, Panagiotis Koutakis, Jennifer L Steiner.

  Chronic alcohol intoxication decreases muscle strength/function and causes mitochondrial dysfunction. Aerobic exercise training improves mitochondrial oxidative capacity and increases muscle mass and strength. Presently, the impact of chronic alcohol on aerobic exercise-induced adaptations was investigated. Female C57BL/6Hsd mice were randomly assigned to one of 4 groups: control sedentary (CON SED; n=26), alcohol sedentary (ETOH SED; n=27), control exercise (CON EX; n=28), and alcohol exercise (ETOH EX; n=25). Exercise mice had running wheel access for 2hrs a day, 7 days a week. All mice were fed either control or alcohol-containing liquid diet. Grip strength testing and EchoMRI were performed before and after the interventions. After 6 weeks, hindlimb muscles were collected for molecular analyses. A subset of mice performed a treadmill run to fatigue (RTF), then abstained from alcohol for 2 weeks and repeated the RTF. Alcohol decreased lean mass and forelimb grip strength compared to control-fed mice. Alcohol blunted the exercise induced increase in muscle mass (plantaris and soleus), type IIa fiber percentage in the plantaris and run time to fatigue. Mitochondrial markers (Citrate synthase activity and Complex I-IV, COXIV and Cytochrome C protein expression), were increased with exercise regardless of ETOH in the gastrocnemius but not tibialis anterior muscle. Two-weeks of alcohol abstinence improved RTF time in ETOH EX but not in ETOH SED. While these data suggest alcohol impairs some exercise-induced adaptations in skeletal muscle, not all were negatively affected, indicating exercise may be a beneficial behavior even while consuming alcohol.

Keywords:  alcohol; endurance performance; ethanol; mitochondria; wheel running

DOI:  https://doi.org/10.1152/japplphysiol.00599.2023
J Appl Physiol (1985). 2024 Feb 01. 136(2): 437-438

Comment on "Fiber-type traps: revisiting common misconceptions about skeletal muscle fiber types with application to motor control, biomechanics, physiology, and biology".

Carlo Reggiani, Marta Murgia.



Keywords:  fiber types; muscle fiber types; myosin isoforms; proteomics; skeletal muscle

DOI:  https://doi.org/10.1152/japplphysiol.00008.2024
Nat Commun. 2024 Feb 15. 15(1): 1393

Neurofibromin 1 controls metabolic balance and Notch-dependent quiescence of murine juvenile myogenic progenitors.

Xiaoyan Wei, Angelos Rigopoulos, Matthias Lienhard, Sophie Pöhle-Kronawitter, Georgios Kotsaris, Julia Franke, Nikolaus Berndt, Joy Orezimena Mejedo, Hao Wu, Stefan Börno, Bernd Timmermann, Arunima Murgai, Rainer Glauben, Sigmar Stricker.

Patients affected by neurofibromatosis type 1 (NF1) frequently show muscle weakness with unknown etiology. Here we show that, in mice, Neurofibromin 1 (Nf1) is not required in muscle fibers, but specifically in early postnatal myogenic progenitors (MPs), where Nf1 loss led to cell cycle exit and differentiation blockade, depleting the MP pool resulting in reduced myonuclear accretion as well as reduced muscle stem cell numbers. This was caused by precocious induction of stem cell quiescence coupled to metabolic reprogramming of MPs impinging on glycolytic shutdown, which was conserved in muscle fibers. We show that a Mek/Erk/NOS pathway hypersensitizes Nf1-deficient MPs to Notch signaling, consequently, early postnatal Notch pathway inhibition ameliorated premature quiescence, metabolic reprogramming and muscle growth. This reveals an unexpected role of Ras/Mek/Erk signaling supporting postnatal MP quiescence in concert with Notch signaling, which is controlled by Nf1 safeguarding coordinated muscle growth and muscle stem cell pool establishment. Furthermore, our data suggest transmission of metabolic reprogramming across cellular differentiation, affecting fiber metabolism and function in NF1.

DOI: https://doi.org/10.1038/s41467-024-45618-z
Hum Mol Genet. 2024 Feb 10. pii: ddae019. [Epub ahead of print]

Muscle eosinophilia is a hallmark of chronic disease in facioscapulohumeral muscular dystrophy.

Andreia M Nunes, Monique M Ramirez, Enrique Garcia-Collazo, Takako Iida Jones, Peter L Jones.

  Facioscapulohumeral muscular dystrophy (FSHD) is a progressive myopathy caused by the aberrant increased expression of the DUX4 retrogene in skeletal muscle cells. The DUX4 gene encodes a transcription factor that functions in zygotic genome activation and then is silenced in most adult somatic tissues. DUX4 expression in FSHD disrupts normal muscle cell function; however, the downstream pathogenic mechanisms are still unclear. Histologically, FSHD affected muscles show a characteristic dystrophic phenotype that is often accompanied by a pronounced immune cell infiltration, but the role of the immune system in FSHD is not understood. Previously, we used ACTA1;FLExDUX4 FSHD-like mouse models varying in severity as discovery tools to identify increased Interleukin 6 and microRNA-206 levels as serum biomarkers for FSHD disease severity. In this study, we use the ACTA1;FLExDUX4 chronic FSHD-like mouse model to provide insight into the immune response to DUX4 expression in skeletal muscles. We demonstrate that these FSHD-like muscles are enriched with the chemoattractant eotaxin and the cytotoxic eosinophil peroxidase, and exhibit muscle eosinophilia. We further identified muscle fibers with positive staining for eosinophil peroxidase in human FSHD muscle. Our data supports that skeletal muscle eosinophilia is a hallmark of FSHD pathology.

Keywords:  FSHD; human disease; immune cell; mouse model

DOI:  https://doi.org/10.1093/hmg/ddae019
Cell Signal. 2024 Feb 13. pii: S0898-6568(24)00065-2. [Epub ahead of print]117 111097

Low-intensity pulsed ultrasound (LIPUS) promotes skeletal muscle regeneration by regulating PGC-1α/AMPK/GLUT4 pathways in satellite cells/myoblasts.

Huimin Duan, Shujie Chen, Xudong Mai, Liping Fu, Liujing Huang, Lanling Xiao, Miaomiao Liao, Hong Chen, Gang Liu, Liwei Xie.

  Low-Intensity Pulsed Ultrasound (LIPUS) holds therapeutic potential in promoting skeletal muscle regeneration, a biological process mediated by satellite cells and myoblasts. Despite their central roles in regeneration, the detailed mechanistic of LIPUS influence on satellite cells and myoblasts are not fully underexplored. In the current investigation, we administrated LIPUS treatment to injured skeletal muscles and C2C12 myoblasts over five consecutive days. Muscle samples were collected on days 6 and 30 post-injury for an in-depth histological and molecular assessment, both in vivo and in vitro with immunofluorescence analysis. During the acute injury phase, LIPUS treatment significantly augmented the satellite cell population, concurrently enhancing the number and size of newly formed myofibers whilst reducing fibrosis levels. At 30 days post-injury, the LIPUS-treated group demonstrated a more robust satellite cell pool and a higher myofiber count, suggesting that early LIPUS intervention facilitates satellite cell proliferation and differentiation, thereby promoting long-term recovery. Additionally, LIPUS markedly accelerated C2C12 myoblast differentiation, with observed increases in AMPK phosphorylation in myoblasts, leading to elevated expression of Glut4 and PGC-1α, and subsequent glucose uptake and mitochondrial biogenesis. These findings imply that LIPUS-induced modulation of myoblasts may culminate in enhanced cellular energy availability, laying a theoretical groundwork for employing LIPUS in ameliorating skeletal muscle regeneration post-injury. NEW & NOTEWORTHY: Utilizing the cardiotoxin (CTX) muscle injury model, we investigated the influence of LIPUS on satellite cell homeostasis and skeletal muscle regeneration. Our findings indicate that LIPUS promotes satellite cell proliferation and differentiation, thereby facilitating skeletal muscle repair. Additionally, in vitro investigations lend credence to the hypothesis that the regulatory effect of LIPUS on satellite cells may be attributed to its capability to enhance cellular energy metabolism.

Keywords:  AMPK; Energy synthesis; Low-intensity pulsed ultrasound; Satellite cell; Skeletal muscle regeneration

DOI:  https://doi.org/10.1016/j.cellsig.2024.111097
Front Neurol. 2024 ;15 1325222

Induced degeneration and regeneration in aged muscle reduce tubular aggregates but not muscle function.

Felipe Tadeu Galante Rocha de Vasconcelos, Antonio Fernando Ribeiro Júnior, Brandow Willy Souza, Isabela de Aquino Zogbi, Laura Machado Lara Carvalho, Letícia Nogueira Feitosa, Lucas Santos Souza, Nathália Gagliardi Saldys, Merari de Fátima Ramires Ferrari, Mariz Vainzof.

   Introduction: Tubular aggregates (TA) are skeletal muscle structures that arise from the progressive accumulation of sarcoplasmic reticulum proteins. Cytoplasmic aggregates in muscle fibers have already been observed in mice and humans, mainly during aging and muscle disease processes. However, the effects of muscle regeneration on TA formation have not yet been reported. This study aimed to investigate the relationship between degeneration/regeneration and TA in aged murine models. We investigated the presence and quantity of TA in old males from two murine models with intense muscle degeneration and regeneration.
Methods: One murine lineage was a Dmdmdx model of Duchenne muscular dystrophy (n = 6). In the other model, muscle damage was induced by electroporation in C57BL/6J wild-type mice, and analyzed after 5, 15, and 30 days post-electroporation (dpe; n = 15). Regeneration was evaluated based on the quantity of developmental myosin heavy chain (dMyHC)-positive fibers.
Results: The frequency of fibers containing TA was higher in aged C57BL/6J (26 ± 8.3%) than in old dystrophic Dmdmdx mice (2.4 ± 2%). Comparing the data from induced degeneration/regeneration in normal mice revealed a reduced proportion of TA-containing fibers after 5 and 30 dpe. Normal aged muscle was able to regenerate and form dMyHC+ fibers, mainly at 5 dpe (0.1 ± 0.1 vs. 16.5 ± 2.6%). However, there was no difference in force or resistance between normal and 30 dpe animals, except for the measurements by the Actimeter device, which showed the worst parameters in the second group.
Discussion: Our results suggest that TA also forms in the Dmdmdx muscle but in smaller amounts. The intense degeneration and regeneration of the old dystrophic model resulted in the generation of new muscle fibers with a lower quantity of TA. Data from electroporated wild-type mice support the idea that muscle regeneration leads to a reduction in the amount of TA. We suggest that TA accumulates in muscle fibers throughout physiological aging and that regeneration leads to the formation of new fibers without these structures. In addition, these new fibers do not confer functional benefits to the muscle.

Keywords:  aging; muscle regeneration; muscular dystrophies; neuromuscular disease; tubular aggregates

DOI:  https://doi.org/10.3389/fneur.2024.1325222
Am J Physiol Endocrinol Metab. 2024 Feb 14.

Disruption of Hepatic Mitochondrial Pyruvate and Amino Acid Metabolism Impairs Gluconeogenesis and Endurance Exercise Capacity in Mice.

Michael R Martino, Mohammad Habibi, Daniel Ferguson, Rita T Brookheart, John P Thyfault, Gretchen A Meyer, Louise Lantier, Curtis C Hughey, Brian N Finck.

  Exercise robustly increases the glucose demands of skeletal muscle. This demand is met not only by muscle glycogenolysis, but also by accelerated liver glucose production from hepatic glycogenolysis and gluconeogenesis to fuel mechanical work and prevent hypoglycemia during exercise. Hepatic gluconeogenesis during exercise is dependent on highly coordinated responses within and between muscle and liver. Specifically, exercise increases the rate at which gluconeogenic precursors such as pyruvate/lactate or amino acids are delivered from muscle to the liver, extracted by the liver, and channeled into glucose. Herein, we examined the effects of interrupting gluconeogenic efficiency and capacity on exercise performance by deleting hepatic mitochondrial pyruvate carrier 2 (MPC2) and/or alanine transaminase 2 (ALT2) in mice. We found that deletion of MPC2 or ALT2 alone did not significantly affect time to exhaustion or post-exercise glucose concentrations in treadmill exercise tests, but mice lacking both MPC2 and ALT2 in liver (DKO) reached exhaustion faster and exhibited lower circulating glucose during and after exercise. Use of ²H/¹³C metabolic flux analyses demonstrated that DKO mice exhibited lower endogenous glucose production owing to decreased glycogenolysis and gluconeogenesis at rest and during exercise. The decreased gluconeogenesis was accompanied by lower anaplerotic, cataplerotic, and TCA cycle fluxes. Collectively, these findings demonstrate that the transition of the liver to the gluconeogenic mode is critical for preventing hypoglycemia and sustaining performance during exercise. The results also illustrate the need for interorgan crosstalk during exercise as described by the Cahill and Cori cycles.

Keywords:  alanine transaminase; exercise; gluconeogenesis; mitochondrial pyruvate carrier

DOI:  https://doi.org/10.1152/ajpendo.00258.2023
FEBS Open Bio. 2024 Feb 17.

Oleanolic acid alleviates obesity-induced skeletal muscle atrophy via the PI3K/Akt signaling pathway.

Yaqin Sun, Xiaofang Wei, Tong Zhao, Hongwei Shi, Xiaojing Hao, Yue Wang, Huiling Zhang, Zhichao Yao, Minxing Zheng, Tianyun Ma, Tingting Fu, Jiayin Lu, Xiaomao Luo, Yi Yan, Haidong Wang.

  Oleanolic acid (OA) is a pentacyclic triterpene with reported protective effects against various diseases, including diabetes, hepatitis, and different cancers. However, the effects of OA on obesity-induced muscle atrophy remain largely unknown. This study investigated the effects of OA on skeletal muscle production and proliferation of C2C12 cells. We report that OA significantly increased skeletal muscle mass and improved glucose intolerance and insulin resistance. OA inhibited dexamethasone (Dex)-induced muscle atrophy in C2C12 myoblasts by regulating the PI3K/Akt signaling pathway. In addition, it also inhibited expression of MuRF1 and Atrogin1 genes in skeletal muscle of obese mice suffering from muscle atrophy, and increased the activation of PI3K and Akt, thereby promoting protein synthesis, and eventually alleviating muscle atrophy. Taken together, these findings suggest OA may have potential for the prevention and treatment of muscle atrophy.

Keywords:  PI3K/Akt signaling pathways; dexamethasone; muscle atrophy; obesity; oleanolic acid

DOI:  https://doi.org/10.1002/2211-5463.13780
Free Neuropathol. 2024 Jan;pii: 5-3. [Epub ahead of print]5

Cellular activation patterns of CD10+ fibro-adipogenic progenitors across acquired disease states in human skeletal muscle biopsies.

Peter W Schutz, Simon Cheung, Lin Yi, Fabio M V Rossi.

  Background: Fibro-adipogenic progenitors (FAP) are muscle resident mesenchymal stem cells pivotal for regulation of myofiber repair. Experimental results show in addition involvement in a range of other pathological conditions and potential for pharmacological intervention. FAP histopathology in human muscle biopsies is largely unknown, but has potential to inform translational research. Methods: CD10+ FAPs in 32 archival muscle biopsies from 8 groups (normal, dermatomyositis, inclusion body myositis (IBM), anti-synthetase syndrome, immune-mediated necrotizing myopathy (IMNM), denervation, type 2 atrophy, rhabdomyolysis) were visualized by CD10 immunohistochemistry and their histology compared. Groups are compared by semi-quantitative scoring. Results: Histological activation of endomysial CD10+ FAPs includes prominent expansion of a network of cell processes surrounding muscle fibers, as well as endomysial cell clusters evidencing proliferation. Prominence of periarteriolar processes is a notable feature in some pathologies. FAP activation is often associated with fiber degeneration/regeneration, foci of inflammation, and denervation in keeping with experimental results. Type 2 atrophy shows no evidence of FAP activation. Dermatomyositis and anti-synthetase syndrome associated myositis demonstrate diffuse activation. Conclusion: Assessment of CD10+ FAP activation is routinely possible using CD10 immunohistochemistry and demonstrates several patterns in keeping with preclinical results. Prominent expansion of FAP processes surrounding myofibers suggests enhanced interaction between myofiber/basement membranes and FAPs during activation. The presence of diffuse FAP activation in dermatomyositis biopsies unrelated to fiber repair raises the possibility of FAP activation as part of the autoimmune process. Future diagnostic applications, clinical significance and therapeutic potential remain to be elucidated.

Keywords:  CD10; Denervation; Fibro-adipogenic progenitor; Inflammatory myopathy; Periarteriolar; Type 2 atrophy

DOI:  https://doi.org/10.17879/freeneuropathology-2024-5162
Front Endocrinol (Lausanne). 2024 ;15 1356312

Passive exercise is an effective alternative to HRT for restoring OVX induced mitochondrial dysfunction in skeletal muscle.

Yi Hu, Biqing Fang, Xu Tian, Haiwei Wang, Xiangyang Tian, Fangfang Yu, Tao Li, Zhijie Yang, Rengfei Shi.

   Background: Postmenopausal women are more prone to develop muscle weakness, which is strongly associated with impairment of mitochondrial function in skeletal muscle. This study aimed to examine the impact of a passive exercise modality, whole-body vibration training (WBVT), on muscle mitochondrial function in ovariectomized (OVX) mice, in comparison with 17β-estradiol (E2) replacement.
Methods: Female C57BL/6J mice were assigned to four groups: sham operation control group (Sham), ovariectomized group (OVX), OVX with E2 supplement group (OVX+E), and OVX with WBVT group (OVX+W). The estrous cycle, body weight, body composition, and muscle strength of the mice were monitored after the operation. Serum E2 level was assessed by enzyme-linked immunosorbent assay (ELISA). The ATP levels were determined using a luciferase-catalyzed bioluminescence assay. The activity of mitochondrial respiration chain complexes was evaluated using high-resolution respirometry (O2K). Expression levels of oxidative phosphorylation (OXPHOS), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), and mitochondrial transcription factor A (TFAM) were detected using western blotting.
Results: We observed decreased muscle strength and impaired mitochondrial function in the skeletal muscle of OVX mice. The vibration training alleviated these impairments as much as the E2 supplement. In addition, the vibration training was superior to the ovariectomy and the estradiol replacement regarding the protein expression of PGC-1α and TFAM.
Conclusion: WBVT improves the OVX-induced decline in muscle strength and impairment of mitochondrial function in the skeletal muscle. This passive exercise strategy may be useful as an alternative to E2 replacement for preventing menopausal muscular weakness. Further studies are needed to understand the effects of WBVT on various physiological systems, and precautions should be taken when implementing it in patient treatment.

Keywords:  17β-estradiol replacement; hormone replacement therapy; mitochondrial function; muscle weakness; ovariectomized mice; passive exercise; whole-body vibration training

DOI:  https://doi.org/10.3389/fendo.2024.1356312
J Sport Health Sci. 2024 Feb 08. pii: S2095-2546(24)00018-8. [Epub ahead of print]

Associations of accelerometry-measured and self-reported physical activity and sedentary behavior with skeletal muscle energetics: The Study of Muscle, Mobility and Aging (SOMMA).

Yujia Susanna Qiao, Terri L Blackwell, Peggy M Cawthon, Paul M Coen, Steven R Cummings, Giovanna Distefano, Samaneh Farsijani, Daniel E Forman, Bret H Goodpaster, Stephen B Kritchevsky, Theresa Mau, Frederico G S Toledo, Anne B Newman, Nancy W Glynn.

   BACKGROUND: Skeletal muscle energetics decline with age, and physical activity (PA) has been shown to offset these declines in older adults. Yet, many studies reporting these effects were based on self-reported PA or structured exercise interventions. Therefore, we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior (SB) with skeletal muscle energetics and explored the extent to which PA and SB would attenuate the associations of age with muscle energetics.
METHODS: As part of the Study of Muscle, Mobility and Aging (SOMMA), enrolled older adults (n = 879), 810 (mean ± SD age = 76 ± 5 years old; 58% women) had maximal muscle oxidative capacity measured ex vivo via high-resolution respirometry of permeabilized myofibers (maximal oxidative phosphorylation (maxOXPHOS)) and in vivo by 31Phosphorus magnetic resonance spectroscopy (maximal adenosine triphosphate (ATPmax)). Accelerometry-measured SB, light activity, and moderate-to-vigorous PA (MVPA) were assessed using a wrist-worn ActiGraph GT9X over 7 days. Self-reported SB, MVPA, and all physical activity were assessed with the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire. Linear regression models with progressive covariate adjustments evaluated the associations of SB and PA with muscle energetics as well as the attenuation of the age/muscle energetics association by MVPA and SB. As a sensitivity analysis, we also examined activPAL-measured daily step count and time spent in SB and their associations with muscle energetics.
RESULTS: Every 30 min/day more of ActiGraph-measured MVPA was associated with 0.65 pmol/s × mg higher maxOXPHOS and 0.012 mM/s higher ATPmax after adjusting for age, site/technician, and sex (p < 0.05). Light activity was not associated with maxOXPHOS or ATPmax. Meanwhile, every 30 min/day spent in ActiGraph-measured SB was associated with 0.39 pmol/s × mg lower maxOXPHOS and 0.006 mM/s lower ATPmax (p < 0.05). Only associations with ATPmax held after further adjusting for socioeconomic status, body mass index, lifestyle factors, and multimorbidity. CHAMPS MVPA and all physical activity yielded similar associations with maxOXPHOS and ATPmax (p < 0.05), but SB did not. Higher activPAL step count was associated with higher maxOXHPOS and ATPmax (p < 0.05), but time spent in SB was not. Additionally, age was significantly associated with muscle energetics for men only (P < 0.05); adjusting for time spent in ActiGraph-measured MVPA attenuated the age association with ATPmax by 58% in men.
CONCLUSION: More time spent in accelerometry-measured or self-reported daily PA, especially MVPA, was associated with higher skeletal muscle energetics. Interventions aimed specifically at increasing higher intensity activity might offer potential therapeutic interventions to slow age-related decline in muscle energetics. Our work also emphasizes the importance of taking PA into consideration when evaluating associations related to skeletal muscle energetics.

Keywords:  Aging; Exercise; Mitochondria

DOI:  https://doi.org/10.1016/j.jshs.2024.02.001
Physiol Rep. 2024 Feb;12(3): e15950

Histological and biochemical changes in lymphatic vessels after skeletal muscle injury induced by lengthening contraction in male mice.

Yuma Tamura, Takafumi Kawashima, Rui-Cheng Ji, Nobuhide Agata, Yuta Itoh, Keisuke Kawakami.

  Lymphatic vessels are actively involved in the recovery process of inflamed tissues. However, the changes in intramuscular lymphatic vessels during inflammation caused by skeletal muscle injury remain unclear. Therefore, the purpose of this study was to clarify the changes in lymphatic vessels after skeletal muscle injury. The left tibialis anterior muscles of male mice were subjected to lengthening contractions (LC) for inducing skeletal muscle injury, and samples were collected on Days 2, 4, and 7 for examining changes in both the skeletal muscles and intramuscular lymphatic vessels. With hematoxylin-eosin staining, the inflammatory response was observed in myofibers on Days 2 and 4 after LC, whereas regeneration of myofibers was found on Day 7 after LC. The number and area of intramuscular lymphatic vessels analyzed by immunohistochemical staining with an antibody against lymphatic vessel endothelial hyaluronan receptor 1 were significantly increased only on Day 4 after LC. Based on the abovementioned results, intramuscular lymphatic vessels undergo morphological changes such as increase under the state of muscle inflammation. This study demonstrated that the morphology of intramuscular lymphatic vessels undergoes significant changes during the initial recovery phase following skeletal muscle injury.

Keywords:  inflammation; lengthening contraction; lymphatic vessels; skeletal muscle injury

DOI:  https://doi.org/10.14814/phy2.15950
Tissue Cell. 2024 Feb 12. pii: S0040-8166(24)00025-9. [Epub ahead of print]87 102324

Lactate induces C2C12 myoblasts differentiation by mediating ROS/p38 MAPK signalling pathway.

Chunfang Cheng, Wenxi Li, Yuanqian Ye, Yuanjie Zhu, Mengyuan Tang, Zhihong Hu, Hu Su, Caixia Dang, Juan Wan, Zhibin Liu, Yanchun Gong, Li-Hua Yao.

  Lactate serves not merely as an energy substrate for skeletal muscle but also regulates myogenic differentiation, leading to an elevation of reactive oxygen species (ROS) levels. The present study was focused on exploring the effects of lactate and ROS/p38 MAPK in promoting C2C12 myoblasts differentiation. Our results demonstrated that lactate increased C2C12 myoblasts differentiation at a range of physiological concentrations, accompanied by enhanced ROS contents. We used n-acetylcysteine (NAC, a ROS scavenger) pretreatment and found that it delayed lactate-induced C2C12 myoblast differentiation by upregulating Myf5 expression on days 5 and 7 and lowering MyoD and MyoG expression. The finding implies that lactate accompanies ROS-dependent manner to promote C2C12 myoblast differentiation. Additionally, lactate significantly increased p38 MAPK phosphorylation to promote C2C12 cell differentiation, but pretreatment with SB203580 (p38 MAPK inhibitor) reduced lactate-induced C2C12 myoblasts differentiation. whereas lactate pretreatment with NAC inhibited p38 MAPK phosphorylation in C2C12 cells, demonstrating that lactate mediated ROS and regulated the p38 MAPK signalling pathway to promote C2C12 cell differentiation. In conclusion, our results suggest that the promotion of C2C12 myoblasts differentiation by lactate is dependent on ROS and the p38 MAPK signalling pathway. These observations reveal a beneficial role for lactate in increasing myogenesis through ROS-sensitive mechanisms as well as providing new ideas regarding the positive impact of ROS in improving the function of skeletal muscle.

Keywords:  C2C12 myoblast; Lactate; Myogenic differentiation; P38 MAPK; ROS

DOI:  https://doi.org/10.1016/j.tice.2024.102324
NPJ Microgravity. 2024 Feb 16. 10(1): 18

Simulated microgravity attenuates myogenesis and contractile function of 3D engineered skeletal muscle tissues.

Zhanping Ren, Eun Hyun Ahn, Minjae Do, Devin B Mair, Amir Monemianesfahani, Peter H U Lee, Deok-Ho Kim.

While the effects of microgravity on inducing skeletal muscle atrophy have been extensively studied, the impacts of microgravity on myogenesis and its mechanisms remain unclear. In this study, we developed a microphysiological system of engineered muscle tissue (EMT) fabricated using a collagen / Matrigel composite hydrogel and murine skeletal myoblasts. This 3D EMT model allows non-invasive quantitative assessment of contractile function. After applying a 7-day differentiation protocol to induce myotube formation, the EMTs clearly exhibited sarcomerogenesis, myofilament formation, and synchronous twitch and tetanic contractions with electrical stimuli. Using this 3D EMT system, we investigated the effects of simulated microgravity at 10-3 G on myogenesis and contractile function utilizing a random positioning machine. EMTs cultured for 5 days in simulated microgravity exhibited significantly reduced contractile forces, myofiber size, and differential expression of muscle contractile, myogenesis regulatory, and mitochondrial biogenesis-related proteins. These results indicate simulated microgravity attenuates myogenesis, resulting in impaired muscle function.

DOI: https://doi.org/10.1038/s41526-024-00353-z
J Gerontol A Biol Sci Med Sci. 2024 Feb 15. pii: glae047. [Epub ahead of print]

Associations of Skeletal Muscle Mass, Muscle Fat Infiltration, Mitochondrial Energetics, and Cardiorespiratory Fitness with Liver Fat Among Older Adults.

Daria Igudesman, Justine Mucinski, Stephanie Harrison, Peggy M Cawthon, Jennifer Linge, Bret H Goodpaster, Steven R Cummings, Russell T Hepple, Michael J Jurczak, Stephen B Kritchevsky, David Marcinek, Paul M Coen, Karen D Corbin.

   BACKGROUND: Muscle mass loss may be associated with liver fat accumulation, yet scientific consensus is lacking and evidence in older adults is scant. It is unclear which muscle characteristics might contribute to this association in older adults.
METHODS: We associated comprehensive muscle-related phenotypes including muscle mass normalized to body weight (D3-creatine dilution), muscle fat infiltration (MRI), carbohydrate-supported muscle mitochondrial maximal oxidative phosphorylation (respirometry), and cardiorespiratory fitness (VO2 peak) with liver fat among older adults. Linear regression models adjusted for age, gender, technician (respirometry only), daily minutes of moderate to vigorous physical activity, and prediabetes/diabetes status tested main effects and interactions of each independent variable with waist circumference (high: women-≥88 cm, men-≥102 cm) and gender.
RESULTS: Among older adults aged 75 (IQR 73, 79 years; 59.8% women), muscle mass and liver fat were not associated overall (N=362) but were positively associated among participants with a high waist circumference (β: 25.2; 95%CI 11.7, 40.4; p=.0002; N=160). Muscle fat infiltration and liver fat were positively associated (β: 15.2; 95%CI 6.8, 24.3; p=.0003; N=378). Carbohydrate-supported maximum oxidative phosphorylation (before adjustment) and VO2 peak (after adjustment; β: -12.9; 95%CI -20.3, -4.8; p=0.003; N=361) were inversely associated with liver fat; adjustment attenuated the estimate for maximum oxidative phosphorylation although the point estimate remained negative (β: -4.0; 95%CI -11.6, 4.2; p=0.32; N=321).
CONCLUSIONS: Skeletal muscle-related characteristics are metabolically relevant factors linked to liver fat in older adults. Future research should confirm our results to determine whether trials targeting mechanisms common to liver and muscle fat accumulation are warranted.

Keywords:  hepatic issues; metabolism; muscle; physical function

DOI:  https://doi.org/10.1093/gerona/glae047
Eur J Transl Myol. 2024 Feb 15.

Role of the ubiquitin-proteasome system in the sarcopenic-like phenotype induced by CCL5/RANTES.

Sabrina Conejeros-Lillo, Francisco Aguirre, Daniel Cabrera, Felipe Simon, Luis Peñailillo, Claudio Cabello-Verrugio.

Sarcopenia is characterized by reduced muscle strength and mass and a decline in muscle fiber diameter and amount of sarcomeric proteins. Sarcopenia involves the activation of the ubiquitin-proteasome system (UPS). MuRF-1 and atrogin-1 are E3 ubiquitin ligases belonging to UPS, leading to proteolysis mediated by the PSMB 5, 6, and 7 subunits of 20S proteasome. CCL5/RANTES induces a sarcopenic-like effect in muscle cells. The present work explored the impact of CCL5 on UPS components and the influence of UPS on its sarcopenic-like effect. We demonstrated that CCL5 increased MuRF-1 and atrogin-1 protein levels and mRNA levels of subunits PSMB 5, 6, and 7. We used the MG132 inhibitor to elucidate the role of the 20S proteasome in the CCL5-induced sarcopenic-like effect. This inhibitor prevented the decrease in troponin and MHC protein levels and partially prevented the reduction in the diameter of single-isolated FDB muscle fibers induced by CCL5. These findings indicate that CCL5 actively modulates the UPS. Moreover, our results show the direct participation of UPS in the sarcopenic-like phenotype induced by CCL5.

DOI: https://doi.org/10.4081/ejtm.2024.12249
Brain. 2024 Feb 15. pii: awae046. [Epub ahead of print]

Biallelic variants in SNUPN cause a limb girdle muscular dystrophy with myofibrillar-like features.

Pablo Iruzubieta, Alberto Damborenea, Mihaela Ioghen, Simon Bajew, Roberto Fernandez-Torrón, Ana Töpf, Álvaro Herrero-Reiriz, Diana Epure, Katharina Vill, Aurelio Hernández-Laín, María Manterola, Mikel Azkargorta, Oihane Pikatza-Menoio, Laura Pérez-Fernandez, Mikel García-Puga, Gisela Gaina, Alexandra Bastian, Ioana Streata, Maggie C Walter, Wolfgang Müller-Felber, Simone Thiele, Saioa Moragón, Nerea Bastida-Lertxundi, Aitziber López-Cortajarena, Felix Elortza, Gorka Gereñu, Sonia Alonso-Martin, Volker Straub, David de Sancho, Raluca Teleanu, Adolfo López de Munain, Lorea Blázquez.

  Alterations in RNA-splicing are a molecular hallmark of several neurological diseases, including muscular dystrophies where mutations in genes involved in RNA metabolism or characterised by alterations in RNA splicing have been described. Here, we present five patients from two unrelated families with a limb-girdle muscular dystrophy (LGMD) phenotype carrying a biallelic variant in SNUPN gene. Snurportin-1, the protein encoded by SNUPN, plays an important role in the nuclear transport of small nuclear ribonucleoproteins (snRNPs), essential components of the spliceosome. We combine deep phenotyping, including clinical features, histopathology and muscle magnetic resonance image (MRI), with functional studies in patient-derived cells and muscle biopsies to demonstrate that variants in SNUPN are the cause of a new type of LGMD according to current definition. Moreover, an in vivo model in Drosophila melanogaster further supports the relevance of Snurportin-1 in muscle. SNUPN patients show a similar phenotype characterised by proximal weakness starting in childhood, restrictive respiratory dysfunction and prominent contractures, although interindividual variability in terms of severity even in individuals from the same family was found. Muscle biopsy showed myofibrillar-like features consisting of myotilin deposits and Z-disc disorganisation. MRI showed predominant impairment of paravertebral, vasti, sartorius, gracilis, peroneal and medial gastrocnemius muscles. Conservation and structural analyses of Snurportin-1 p.Ile309Ser variant suggest an effect in nuclear-cytosol snRNP trafficking. In patient-derived fibroblasts and muscle, cytoplasmic accumulation of snRNP components is observed, while total expression of Snurportin-1 and snRNPs remains unchanged, which demonstrates a functional impact of SNUPN variant in snRNP metabolism. Furthermore, RNA-splicing analysis in patients' muscle showed widespread splicing deregulation, in particular in genes relevant for muscle development and splicing factors that participate in the early steps of spliceosome assembly. In conclusion, we report that SNUPN variants are a new cause of limb girdle muscular dystrophy with specific clinical, histopathological and imaging features, supporting SNUPN as a new gene to be included in genetic testing of myopathies. These results further support the relevance of splicing-related proteins in muscle disorders.

Keywords:  Snurportin-1; myopathy; small-nuclear ribonucleoproteins (snRNPs); splicing

DOI:  https://doi.org/10.1093/brain/awae046
Mol Metab. 2024 Feb 10. pii: S2212-8778(24)00030-9. [Epub ahead of print] 101899

Treatment of infantile-onset Pompe disease in a rat model with muscle-directed AAV gene therapy.

Sergio Muñoz, Joan Bertolin, Veronica Jimenez, Maria Luisa Jaén, Miquel Garcia, Anna Pujol, Laia Vilà, Victor Sacristan, Elena Barbon, Giuseppe Ronzitti, Jihad El Andari, Warut Tulalamba, Quang Hong Pham, Jesus Ruberte, Thierry VandenDriessche, Marinee K Chuah, Dirk Grimm, Federico Mingozzi, Fatima Bosch.

   OBJECTIVE: Pompe disease (PD) is caused by deficiency of the lysosomal enzyme acid α-glucosidase (GAA), leading to progressive glycogen accumulation and severe myopathy with progressive muscle weakness. In the Infantile-Onset PD (IOPD), death generally occurs <1 year of age. There is no cure for IOPD. Mouse models of PD do not completely reproduce human IOPD severity. Our main objective was to generate the first IOPD rat model to assess an innovative muscle-directed adeno-associated viral (AAV) vector-mediated gene therapy.
METHODS: PD rats were generated by CRISPR/Cas9 technology. The novel highly myotropic bioengineered capsid AAVMYO3 and an optimized muscle-specific promoter in conjunction with a transcriptional cis-regulatory element were used to achieve robust Gaa expression in the entire muscular system. Several metabolic, molecular, histopathological, and functional parameters were measured.
RESULTS: PD rats showed early-onset widespread glycogen accumulation, hepato- and cardiomegaly, decreased body and tissue weight, severe impaired muscle function and decreased survival, closely resembling human IOPD. Treatment with AAVMYO3-Gaa vectors resulted in widespread expression of Gaa in muscle throughout the body, normalizing glycogen storage pathology, restoring muscle mass and strength, counteracting cardiomegaly and normalizing survival rate.
CONCLUSIONS: This gene therapy holds great potential to treat glycogen metabolism alterations in IOPD. Moreover, the AAV-mediated approach may be exploited for other inherited muscle diseases, which also are limited by the inefficient widespread delivery of therapeutic transgenes throughout the muscular system.

Keywords:  AAV; Gene therapy; Glycogen metabolism; Myopathies; Pompe disease; Rat model

DOI:  https://doi.org/10.1016/j.molmet.2024.101899
J Cell Sci. 2024 Feb 12. pii: jcs.261666. [Epub ahead of print]

Culture substrate stiffness impacts human myoblast contractility-dependent proliferation and nuclear envelope wrinkling.

Jo Nguyen, Lu Wang, Wen Lei, Yechen Hu, Nitya Gulati, Carolina Chavez-Madero, Henry Ahn, Howard J Ginsberg, Roman Krawetz, Matthias Brandt, Timo Betz, Penney M Gilbert.

  Understanding how biophysical and biochemical microenvironmental cues together influence the regenerative activities of muscle stem cells and their progeny is crucial in strategizing remedies for pathological dysregulation of these cues in aging and disease. In this study, we investigated the cell-level influences of extracellular matrix ligands and culture substrate stiffness on primary human myoblast contractility and proliferation within 16 hours of plating and found that tethered fibronectin led to stronger stiffness-dependent responses compared to laminin and collagen. A proteome-wide analysis further uncovered cell metabolism, cytoskeletal, and nuclear component regulation distinctions between cells cultured on soft and stiff substrates. Interestingly, we found that softer substrates increased the incidence of myoblasts with a wrinkled nucleus, and that the extent of wrinkling could predict Ki67 expression. Nuclear wrinkling and Ki67 expression could be controlled by pharmacological manipulation of cellular contractility offering a potential cellular mechanism. These results provide new insights into the regulation of human myoblast stiffness-dependent contractility response by ECM ligands and highlight a link between myoblast contractility and proliferation.

Keywords:  Cell contractility; Extracellular matrix; Mechanobiology; Myoblast; Nuclear envelope; Substrate stiffness

DOI:  https://doi.org/10.1242/jcs.261666
J Lipid Res. 2024 Feb 12. pii: S0022-2275(24)00024-5. [Epub ahead of print] 100519

Decreased sarcoplasmic reticulum phospholipids in human skeletal muscle are associated with metabolic syndrome.

Samantha E Adamson, Sangeeta Adak, Max C Petersen, Dustin Higgins, Larry D Spears, Rong Mei Zhang, Andrea Cedeno, Alexis McKee, Aswathi Kumar, Sudhir Singh, Fong-Fu Hsu, Janet B McGill, Clay F Semenkovich.

  Metabolic syndrome affects more than one in three adults and is associated with increased risk of diabetes, cardiovascular disease, and all-cause mortality. Muscle insulin resistance is a major contributor to the development of the metabolic syndrome. Studies in mice have linked skeletal muscle sarcoplasmic reticulum (SR) phospholipid composition to sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity and insulin sensitivity. To determine if the presence of metabolic syndrome alters specific phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species in human sarcoplasmic reticulum (SR), we compared SR phospholipid composition in skeletal muscle from sedentary subjects with metabolic syndrome and sedentary control subjects without metabolic syndrome. Both total PC and total PE were significantly decreased in skeletal muscle SR of sedentary metabolic syndrome patients compared to sedentary controls, particularly in female participants, but there was no difference in the PC:PE ratio between groups. Total SR PC levels, but not total SR PE levels or PC:PE ratio, were significantly negatively correlated with BMI, waist circumference, total fat, visceral adipose tissue, triglycerides, fasting insulin and HOMA-IR. These findings are consistent with the existence of a relationship between skeletal muscle SR PC content and insulin resistance in humans.

Keywords:  diabetes; insulin resistance; muscle; phospholipids/phosphatidylcholine

DOI:  https://doi.org/10.1016/j.jlr.2024.100519
Comp Biochem Physiol B Biochem Mol Biol. 2024 Feb 13. pii: S1096-4959(24)00019-8. [Epub ahead of print]272 110952

Dramatic genome-wide reprogramming of mRNA in hypometabolic muscle.

Nicholas J Hudson, Rebecca L Cramp, Craig E Franklin.

  In response to seasonal droughts, the green striped burrowing frog Cyclorana alboguttata enters a reversible hypometabolic state called aestivation where heart rate and oxygen consumption can be reduced despite warm (>25C°) ambient temperatures. With a view to understanding molecular mechanisms we profiled aestivating versus control gastrocnemius muscle using mRNA sequencing. This indicated an extensive metabolic reprogramming, with nearly a quarter of the entire transcriptome (3996 of 16,960 mRNA) exhibiting a nominal >2-fold change. Consistent with a physiological adaptation to spare carbohydrate reserves, carbohydrate catabolism was systemically downregulated. A 630-fold downregulation of ENO3 encoding the enolase enzyme was most striking. The 590 frog orthologs of mRNA encoding the mitoproteome were, viewed as a population, significantly downregulated during aestivation, although not to the same extent as mRNA encoding carbohydrate catabolism. Prominent examples include members of the TCA cycle (IDH2), electron transport chain (NDUFA6), the ATP synthase complex (ATP5F1B) and ADP/ATP intracellular transport (SLC25A4). Moreover, mRNA derived from the mt genome itself (e.g. mt-ND1) were also downregulated. Most prominent among the upregulated mRNA are those encoding aspects of regulated proteolysis including the proteosome (e.g. PSME4L), peptidases (USP25), atrogins (FBXO32) and ubiquitination (VCP). Finally, we note the ∼5-fold upregulation of the mRNA EIFG3 that encodes part of the EIF4F complex. This possesses global control of protein synthesis. Given protein synthesis is repressed in aestivating frogs this indicates the skeletal musculature is poised for accelerated translation of mRNA upon emergence, supporting a strategy to rapidly restore function when the summer rains come.

Keywords:  Aestivation; Glycolysis; Metabolic depression; Mitochondria

DOI:  https://doi.org/10.1016/j.cbpb.2024.110952
J Muscle Res Cell Motil. 2024 Feb 14.

The 50th anniversary of the European Society for Muscle Research: a journey through half a century of scientific advances.

Ger Stienen, Carlo Reggiani.

  The European Society for Muscle Research (ESMR) started in 1971 as "European Muscle Club" in a joint initiative of Marcus Schaub, Eduard Jenny and Rudolf Billeter (Zurich), Caspar Rüegg (Heidelberg), Jean Légér (Montpellier), Bernard Swynghedauw (Paris), George Maréchal (Brussels), Gabriel Hamoir (Liège), and Endre Biró (Budapest). Since 1972, local organizers took care of muscle conferences held yearly in different European countries and in Israel in 1987. One of the goals was to establish contacts and collaborations between scientists on both sides of the Iron Curtain. Starting as an informal club, enthusiastically guided by Marcus Schaub as secretary (1971-1995) and later by Ger Stienen (1996-2005), Anders Arner (2006-2017) and Wolfgang Linke (2018-), the ESMR meetings steered international collaborations. The meetings witnessed the remarkable advancement of the insight in skeletal, smooth and cardiac muscle structure and function. In the five decades, the thin and thick filament structure has been resolved to the atomic level, the mechanism of acto-myosin energy transduction and force generation as well as its regulation have been elucidated. The molecular basis of striated and smooth muscle diversity has been found in the existence of multiple protein isoforms. The transcriptional, translational and post-translational regulations which give rise to adaptive responses of muscle tissue have been revealed. Many new players entered the field, such as titin, the ryanodine receptor and several signalling factors. Substantial progress has also been made in the identification of the pathogenesis of many hereditary muscle diseases such as Duchenne MuscularDystrophy and Hypertrophic Cardiac Myopathies.

Keywords:  History; Muscle; Myology

DOI:  https://doi.org/10.1007/s10974-024-09666-8