bims-musmir Biomed News
on microRNAs in muscle
Issue of 2025–06–01
seven papers selected by
Katarzyna Agnieszka Goljanek-Whysall, University of Galway
  1. Associations of Elevated Red Cell Distribution Width (RDW) with Decreased Physical and Cognitive Function in Older Adults, and The Potential Mediation by Mitochondrial Energetics: The Study of Muscle, Mobility and Aging (SOMMA).
  2. Skeletal muscle endothelial dysfunction through the activin A-PGC1α axis drives progression of cancer cachexia.
  3. The extent of Skeletal muscle wasting in prolonged critical illness and its association with survival: insights from a retrospective single-center study.
  4. Characterizing local antibody responses in the muscle of inclusion body myositis patients.
  5. Training-induced plasma miR-29a-3p is secreted by skeletal muscle and contributes to metabolic adaptations to resistance exercise in mice.
  6. Telomere Length, Oxidative Stress Markers, and Related miRNAs in Non-Invasive Samples of Mild COVID-19 Cases.
  7. Angiotensin II Type 1 Receptor Blocker Usage Prevents Oxidative Stress and Muscle Dysfunction in HIV.
  1. Aging Dis. 2025 May 15.
    Associations of Elevated Red Cell Distribution Width (RDW) with Decreased Physical and Cognitive Function in Older Adults, and The Potential Mediation by Mitochondrial Energetics: The Study of Muscle, Mobility and Aging (SOMMA).
    Kyoung Min Kim, Li-Yung Lui, Theresa Mau, Paul M Coen, Steven R Cummings.
      We analyzed the association between RDW and skeletal muscle mitochondrial energetics and how skeletal muscle mitochondrial energetics may mediate the associations of RDW with physical and cognitive performance. The study analyzed cross-sectional baseline data from the Study of Muscle, Mobility and Aging (SOMMA) that enrolled 864 participants aged 70 and older (mean=76.3 years). RDW, clinical and demographic parameters were assessed. Comprehensive evaluations were conducted for both physical and cognitive function using objective and subjective measures. Elevated RDW values were significantly correlated with decreased physical performance, evidenced by reduced cardiorespiratory fitness (VO2peak) and longer time to 400 m Walk, alongside impaired cognitive performance. Higher RDW values also demonstrated robust negative associations with various measurements of mitochondrial energetics, including maximal ATP production and oxidative phosphorylation. Mediation analysis revealed that impaired mitochondrial function partly mediated the associations between RDW values and VO2peak, and other physical and cognitive performance. These findings suggest that higher RDW is associated with declines in various physical and cognitive performance, with skeletal muscle mitochondrial energetics serving as a potential mediating factor. Causal inferences about potential mediation are limited by the cross-sectional design of the study. Nevertheless, the findings highlight the value of RDW as a potential biomarker for age-related declines in physical and cognitive function partly mediated by mitochondrial energetics.
    DOI:  https://doi.org/10.14336/AD.202
  2. Nat Cancer. 2025 May 26.
    Skeletal muscle endothelial dysfunction through the activin A-PGC1α axis drives progression of cancer cachexia.
    Young-Mee Kim, Mark A Sanborn, Shaluah Vijeth, Priyanka Gajwani, Xinge Wang, Dahee Jung, Tibor Valyi-Nagy, Sreeparna Chakraborty, Georgina Mancinelli, Peter T Toth, Evan H Phillips, Paul Grippo, Ameen A Salahudeen, Jooman Park, Su Yeon Yeon, Vijayalakshmi Ananthanarayanan, Yuwei Jiang, Steve Seung-Young Lee, Klara Valyi-Nagy, Jalees Rehman.
      Cachexia is the wasting of skeletal muscle in cancer and is a major complication that impacts a person's quality of life. We hypothesized that cachexia is mediated by dysfunction of the vascular system, which is essential for maintaining perfusion and tempering inappropriate immune responses. Using transparent tissue topography, we discovered that loss of muscle vascular density precedes muscle wasting in multiple complementary tumor models, including pancreatic adenocarcinoma, colon carcinoma, lung adenocarcinoma and melanoma models. We also observed that persons suffering from cancer cachexia exhibit substantial loss of muscle vascular density. As tumors progress, increased circulating activin A remotely suppresses the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) in the muscle endothelium, thus inducing vascular leakage. Restoring endothelial PGC1α activity preserved vascular density and muscle mass in tumor-bearing mice. Our study suggests that restoring muscle endothelial function could be a valuable therapeutic approach for cancer cachexia.
    DOI:  https://doi.org/10.1038/s43018-025-00975-6
  3. BMC Anesthesiol. 2025 May 26. 25(1): 266
    The extent of Skeletal muscle wasting in prolonged critical illness and its association with survival: insights from a retrospective single-center study.
    Johannes Kolck, Clarissa Hosse, Uli Fehrenbach, Nick-Lasse Beetz, Timo Alexander Auer, Christian Pille, Dominik Geisel.
       OBJECTIVE: Muscle wasting in critically ill patients, particularly those with prolonged hospitalization, poses a significant challenge to recovery and long-term outcomes. The aim of this study was to characterize long-term muscle wasting trajectories in ICU patients with acute respiratory distress syndrome (ARDS) due to COVID-19 and acute pancreatitis (AP), to evaluate correlations between muscle wasting and patient outcomes, and to identify clinically feasible thresholds that have the potential to enhance patient care strategies.
    MATERIALS AND METHODS: A collective of 154 ICU patients (100 AP and 54 COVID-19 ARDS) with a minimum ICU stay of 10 days and at least three abdominal CT scans were retrospectively analyzed. AI-driven segmentation of CT scans quantified changes in psoas muscle area (PMA). A mixed model analysis was used to assess the correlation between mortality and muscle wasting, Cox regression was applied to identify potential predictors of survival. Muscle loss rates, survival thresholds and outcome correlations were assessed using Kaplan-Meier and receiver operating characteristic (ROC) analyses.
    RESULTS: Muscle loss in ICU patients was most pronounced in the first two weeks, peaking at -2.42% and - 2.39% psoas muscle area (PMA) loss per day in weeks 1 and 2, respectively, followed by a progressive decline. The median total PMA loss was 48.3%, with significantly greater losses in non-survivors. Mixed model analysis confirmed correlation of muscle wasting with mortality. Cox regression identified visceral adipose tissue (VAT), sequential organ failure assessment (SOFA) score and muscle wasting as significant risk factors, while increased skeletal muscle area (SMA) was protective. ROC and Kaplan-Meier analyses showed strong correlations between PMA loss thresholds and survival, with daily loss > 4% predicting the worst survival (39.7%).
    CONCLUSIONS: To our knowledge, This is the first study to highlight the substantial progression of muscle wasting in prolonged hospitalized ICU patients. The mortality-related thresholds for muscle wasting rates identified in this study may provide a basis for clinical risk stratification. Future research should validate these findings in larger cohorts and explore strategies to mitigate muscle loss.
    CLINICAL TRIAL NUMBER: Not applicable.
    Keywords:  Acute pancreatitis; Artificial intelligence; COVID-19; Computed tomography; Critical care; Muscle wasting
    DOI:  https://doi.org/10.1186/s12871-025-03142-7
  4. J Autoimmun. 2025 May 26. pii: S0896-8411(25)00082-4. [Epub ahead of print]154 103437
    Characterizing local antibody responses in the muscle of inclusion body myositis patients.
    Sahana Jayaraman, Andrew Wilson, Xuwen Alice Zheng, Janelle M Montagne, Iago Pinal-Fernandez, Andrew L Mammen, Thomas E Lloyd, H Benjamin Larman.
       OBJECTIVE: Sporadic inclusion body myositis (IBM) is the most common adult idiopathic inflammatory myopathy. IBM etiology has been elusive, due to both degenerative and autoimmune disease features found on muscle biopsy, and significant disease heterogeneity. Investigating the role of antibodies in the muscle of IBM patients may improve our understanding of disease pathogenesis.
    METHODS: We used an IBM xenograft mouse model in which muscle biopsy tissue from IBM patients (n = 98) and controls (n = 131; including 54 from other types of myopathy) were implanted into immunodeficient mice (NOD-Rag1null-IL2rγnull). We quantified the amount of human IgG, IgA, and IgM in xenografted mouse sera using MesoScale Diagnostics (MSD) assay. We detected donor-derived antibody reactivities targeting autoantigens and infectious agents using Phage ImmunoPrecipitation Sequencing (PhIP-Seq). Finally, we used FR3 AmplifiKation Sequencing (FR3AK-Seq) to sequence the antibody mRNAs from a separate cohort of 146 patient biopsies (14 IBM, 22 healthy controls, 110 other myositis subtypes).
    RESULTS: With the MSD assay we found human IgG, IgA, and IgM in a larger percentage of IBM xenografted mice versus controls. Using PhIP-Seq, we found anti-microbial reactivities secreted from IBM muscle are prevalent amongst a healthy control population but autoantigen reactivities in IBM are more unique at the peptide and protein level. Additionally, NT5C1A (IgG/IgA and IgM) and TIF1γ (IgG/A) autoantibodies are secreted from muscle tissues of 4/18 and 10/18 IBM xenograft donors, respectively.
    CONCLUSION: Our characterization of antibody responses within the muscle of IBM patients reveals that muscle-infiltrating B cells produce both disease-associated autoantibodies and a broad spectrum of antibodies targeting non-self antigens.
    Keywords:  Antibodies; Antibody-profiling technologies; Muscle-specific immune response; Myositis; Reactome profiling; Repertoire sequencing
    DOI:  https://doi.org/10.1016/j.jaut.2025.103437
  5. Mol Metab. 2025 May 23. pii: S2212-8778(25)00080-8. [Epub ahead of print] 102173
    Training-induced plasma miR-29a-3p is secreted by skeletal muscle and contributes to metabolic adaptations to resistance exercise in mice.
    Paola Pinto-Hernandez, Manuel Fernandez-Sanjurjo, Daan Paget, Xurde M Caravia, David Roiz-Valle, Juan Castilla-Silgado, Sergio Diez-Robles, Almudena Coto-Vilcapoma, David Fernandez-Vivero, Pau Gama-Perez, Pablo M Garcia-Roves, Carlos Lopez-Otin, Juleen Zierath, Anna Krook, Benjamin Fernandez-Garcia, Cristina Tomas-Zapico, Eduardo Iglesias-Gutierrez.
      It remains unclear whether the adaptive response to different exercise models is mediated by extracellular vesicle (EV) microRNAs (miRNAs) released from skeletal muscle and their functional metabolic role. We sequenced miRNA-loaded plasma EVs obtained from mice after 4-weeks of endurance or resistance training. Resistance exercise increased the expression of a 11-miRNA profile grouped into two functional clusters. Using both genetically modified murine and cellular models, we have identified miR-29a-3p as a molecular mediator released in EVs in response to skeletal muscle contraction. Moreover, miR-29a-3p also seems to have a relevant role in the adaptation to resistance training by contributing to modulate the expression and secretion of other miRNAs and energy metabolism in muscle and liver. Taken together, our study suggests miR-29a-3p as a training-induced molecular mediator in the response and adaptation to resistance training, possibly due to its regulatory role in energy metabolism.
    Keywords:  energy metabolism; exercise training; extracellular vesicles; miR-29 family; microRNAs
    DOI:  https://doi.org/10.1016/j.molmet.2025.102173
  6. Int J Mol Sci. 2025 May 21. pii: 4934. [Epub ahead of print]26(10):
    Telomere Length, Oxidative Stress Markers, and Related miRNAs in Non-Invasive Samples of Mild COVID-19 Cases.
    Angélica Domínguez-de-Barros, Candela Sirvent-Blanco, Omar García-Pérez, Malena Gajate-Arenas, Alma García-Ramos, Claudia Migliazzo, José E Piñero, Jacob Lorenzo-Morales, Elizabeth Córdoba-Lanús.
      Oxidative stress and inflammation influence immune response and epigenetic mechanisms in infectious diseases. In mild COVID-19, host-encoded miRNA profiles remain underexplored, although they reveal mechanistic insights into disease pathogenesis. This study evaluated ageing and oxidative stress biomarkers (telomere length (TL), TBARS, 8-OHdG, and circulating related-miRNA expression) in 75 mild cases and 30 non-COVID-19 controls. TL correlated with age (R = -0.384, p = 0.005) and was shorter in cases compared to controls (rTL 1.46 ± 0.51 vs. 0.99 ± 0.37; p < 0.001), being similar between saliva and blood samples (p = 0.917). miR-138-5p was upregulated in COVID-19 cases (p = 0.026) and correlated with 8-OHdG (R = 0.403, p = 0.05), which was increased in cases (p = 0.040); miR-210-3p was downregulated in infected individuals (p = 0.008), while miR-182-5p expression correlated with TBARS (R = 0.582, p = 0.018). miR-34a-5p and miR155-5p expression was not altered in mild COVID-19. These findings suggest early systemic cellular damage in mild COVID-19 and highlight miR-138-5p and miR-182-5p as potential early biomarkers of oxidative stress.
    Keywords:  SARS-CoV2; biomarkers; infection response; microRNAs; oxidative stress
    DOI:  https://doi.org/10.3390/ijms26104934
  7. Fundam Clin Pharmacol. 2025 Aug;39(4): e70016
    Angiotensin II Type 1 Receptor Blocker Usage Prevents Oxidative Stress and Muscle Dysfunction in HIV.
    Rafael Deminice, Paola Sanches Cella, Ana Lúcia Borsari, Camila S Padilha, Vitor Hugo Fernando de Oliveira.
       BACKGROUND: We aimed to elucidate the role of Angiotensin II type 1 receptor (AT1R) blocker usage in muscle wasting and dysfunction related to HIV.
    RESEARCH DESIGN AND METHODS: Appendicular skeletal muscle mass, higher and lower limb strength, and physical fitness were determined in people living with HIV (PWH) using AT1R blockers users (n = 33), angiotensin-converting enzyme (ACE) inhibitors (n = 28), or not using antihypertensive drugs (n = 33). Groups had similar age, sex, race, BMI, and time of HIV infection. Muscle biopsies were performed to determine the abundance of AT1R, the relative abundance of selected proteins related to proteolysis, antioxidant enzymes, and oxidative stress. Plasma angiotensin II, IL-6, and TNF-alpha were also determined.
    RESULTS: PWH using AT1R blocker presented higher strength, physical fitness, and muscle mass than PWH using ACE inhibitors or not using antihypertensive drugs. Although both PWH using AT1R blockers and ACE inhibitors presented reduced angiotensin II plasma levels, only PWH using AT1R blockers presented lower skeletal muscle AT1R activation, lower plasma oxidative stress markers, lower skeletal muscle oxidative stress (4-HNE), and proteolysis markers (Atrogin-1, Murf-1).
    CONCLUSION: AT1R blocker usage protects against oxidative stress and activated proteolysis, contributing to the prevention of muscle wasting and dysfunction among PWH.
    Keywords:  HIV; hypertension; renin‐angiotensin system; sarcopenia
    DOI:  https://doi.org/10.1111/fcp.70016
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