bims-musmir 2026-07-05 papers

bims-musmir

Biomed News

on microRNAs in muscle

Issue of 2026–07–05
twelve papers selected by
Katarzyna Agnieszka Goljanek-Whysall, University of Galway

Role of ceramides in cancer cachexia.
Impairments in mitochondrial dynamics and morphology in skeletal muscle of breast cancer patients after a single paclitaxel administration.
Functional Outcomes and Quality of Life for Patients With Cachexia and Solid Tumour Cancers: Findings of a Systematic Literature Review.
Females Are Completely Resistant to Semaglutide-Induced Muscle Loss in ob/ob Mice.
Squalene Alleviates Cancer Cachexia-Induced Muscle Atrophy and Adipose Tissue Wasting in CT26 Tumor-Bearing Mice.
Longitudinal changes of skeletal muscle mass and architecture in critically ill adults: A prospective matched cohort study.
A human lysosomal storage disorder toolkit for decoding proteome landscapes in cortical-like and dopaminergic-like induced neurons.
Chronic hyperinsulinemia accelerates adipose senescence via mitochondrial dysfunction and cGAS-STING signalling.
Utrophin requires α-Syntrophin to maintain neuromuscular junction integrity in mdx mice.
Protein arginine methyltransferases coordinate mitochondrial stress adaptation and neuromuscular function.
Angiogenin mediates cell-cell fusion as a mitochondrial RNA processing enzyme.
Motor unit behavior adaptations across lifespan: sex differences in young, middle-aged and old adults.

Lab Anim (NY). 2026 Jul;55(7): 243

Role of ceramides in cancer cachexia.

Alexandra Le Bras.

DOI: https://doi.org/10.1038/s41684-026-01768-9
Exp Physiol. 2026 Jul 01.

Impairments in mitochondrial dynamics and morphology in skeletal muscle of breast cancer patients after a single paclitaxel administration.

Joris Mallard, Elyse Hucteau, Laura Somme, Hervé Bischoff, Valérie Demais, Pauline Silvestrin, Anne-Laure Charles, Roland Schott, Xavier Pivot, Thomas J Hureau, Allan F Pagano.

  Standard chemotherapy regimens for patients with breast cancer are based on epirubicin-cyclophosphamide (EC) and paclitaxel (TAX) administrations. While it has been shown that first EC administration impairs mitochondrial homeostasis, the isolated effects of TAX have not been studied without previous chemotherapy exposure. We conducted a prospective clinical study including five patients with breast cancer who underwent two vastus lateralis muscle biopsies before and 4 days after the first TAX administration, without any prior chemotherapy exposure. Mitochondrial respiratory capacity, reactive oxygen species production, mitochondrial dynamics and ultrastructure, and apoptosis were assessed using high-resolution respirometry, western blotting, transmission electron microscopy, and TUNEL assay, respectively. Post-TAX, the number of intermyofibrillar mitochondria decreased (-18%; P = 0.049), while the proportion of damaged mitochondria increased (+34%; P = 0.012). Mitochondrial area, perimeter and major/minor axis lengths increased (P < 0.05) while intermyofibrillar cristae area decreased (4.29% pre-TAX vs. 2.60% post-TAX; P = 0.044). Despite these morphological changes, oxidative phosphorylation capacity and respiratory control ratio remained unchanged, whereas complex I-linked substrate respiration decreased (-29%; P = 0.046). MFN2 (-43%; P = 0.040) and Fis1 (-46%; P = 0.046) protein levels decreased post-TAX while mitophagy markers were unchanged. Apoptosis was increased, as documented by increased Bax (+58%; P = 0.045) and TUNEL-positive nuclei (+395%; P = 0.041). In only 4 days, the first TAX administration induced severe skeletal muscle mitochondrial remodelling in patients with breast cancer, characterized by impaired mitochondrial dynamics that resulted in swollen and damaged organelles. These findings demonstrate that mitochondrial toxicity, classically documented at the end of treatment, occurs acutely and after only one chemotherapy administration.

Keywords:  chemotherapy; mitochondrial dynamics; mitochondrial function; muscle biopsies; muscle homeostasis; skeletal muscle deconditioning

DOI:  https://doi.org/10.1113/EP093922
J Cachexia Sarcopenia Muscle. 2026 Aug;17(4): e70319

Functional Outcomes and Quality of Life for Patients With Cachexia and Solid Tumour Cancers: Findings of a Systematic Literature Review.

Jeffrey Crawford, Marie Fallon, Jarjieh Fang, John D Groarke, Karen Smoyer, Tateaki Naito, Ira A Jacobs.

   BACKGROUND: Cachexia, a complex multifactorial syndrome characterized by loss of skeletal muscle mass, is common in cancer and impacts treatment response, quality of life (QoL) and survival. No effective therapy is currently available. This report summarizes findings from the literature on the relationship between cachexia and physical function, activities of daily living and health-related QoL in patients with solid tumours.
METHODS: We conducted a systematic literature review by searching Embase, MEDLINE and Cochrane Library publications from 2018-2023 for relevant studies. After screening and data extraction, a narrative synthesis was performed to identify QoL and functional outcomes in relation to cachexia.
RESULTS: Forty publications representing 37 unique studies and 52 053 patients were identified, with 35 (94.6%) observational studies and two (5.4%) post hoc analyses of randomized trials ranging in sample size from 38 to approximately 17 000 patients. Mean/median patient age ranged from 45 to 79.6 years. Across the 40 publications, 11 different definitions of cachexia or body weight loss were used (with the most common, the Fearon et al. 2011 International Consensus criteria, used in 18 publications [45.0%]), revealing an overall lack of consensus on the most suitable diagnostic criteria for cachexia. Nineteen outcome types were reported, including physical function measures in 31 studies (77.5%), health-related QoL in 24 studies (60.0%), performance status in 16 studies (40.0%), pain and fatigue in 15 studies (37.5%) each, depression or anxiety in nine studies (22.5%) and activities of daily living in six studies (15.0%). Eleven outcome types were exclusively evaluated in univariate analysis; eight were evaluated in multivariate analysis. Many studies identified statistically significantly worse physical function, activities of daily living or health-related QoL in patients with cachexia or body weight loss compared with patients without these conditions. Of studies assessing physical function measures, 80.6% (25/31) identified a statistically significant association with cachexia or body weight loss in at least one outcome; for studies assessing health-related QoL, this was 91.7% (22/24); for performance status, 87.5% (14/16); for pain, 78.6% (11/14); for fatigue, 73.3% (11/15); for depression or anxiety, 55.6% (5/9); and for activities of daily living, 100% (6/6).
CONCLUSIONS: This systematic literature review provides insights into functional outcomes and health-related QoL in predominantly real-world populations with cancer cachexia and can inform selection of cachexia clinical trial endpoints that reflect clinical benefits to patients. However, the wide range of methods, physical function metrics and patient-reported outcomes instruments used across studies support a call for standardization.

Keywords:  cachexia; cancer; health‐related quality of life; physical function; weight loss

DOI:  https://doi.org/10.1002/jcsm.70319
Diabetes. 2026 Jul 02. pii: db260229. [Epub ahead of print]

Females Are Completely Resistant to Semaglutide-Induced Muscle Loss in ob/ob Mice.

Subhasmita Rout, Takuya Karasawa, Shinya Watanabe, Amandine Chaix, Micah J Drummond, Katsuhiko Funai, Ran Hee Choi.

ARTICLE HIGHLIGHTS: Female C57BL/6 J mice are relatively resistant to weight gain, which complicates the study of sex-specific metabolic responses. So, we used ob/ob mice to examine semaglutide-induced weight loss in both sexes. We wanted to determine whether semaglutide-induced weight loss produces sex-specific effects on skeletal muscle mass and function in ob/ob mice. Semaglutide had minimal effects on skeletal muscle mass and strength in ob/ob mice. In particular, females were completely resistant to loss of muscle mass. These findings reveal that semaglutide exerts sex-specific effects, highlighting a need for further research into the molecular mechanisms driving these distinct protective outcomes.

DOI: https://doi.org/10.2337/db26-0229
J Nutr Biochem. 2026 Jun 29. pii: S0955-2863(26)00199-3. [Epub ahead of print] 110457

Squalene Alleviates Cancer Cachexia-Induced Muscle Atrophy and Adipose Tissue Wasting in CT26 Tumor-Bearing Mice.

Yeeun Kim, Junhui Kang, Sungmin Han, Junhee Lee, Hyunju Kang, Jae-Kwan Hwang, Mi-Bo Kim.

  Cancer cachexia is a multifactorial metabolic syndrome characterized by progressive loss of body weight, skeletal muscle, and adipose tissue, primarily driven by chronic inflammation and systemic energy imbalance. Squalene (SQ), a naturally occurring triterpenoid abundant in shark liver oil, exhibits potent antioxidant and anti-inflammatory properties. In this study, we investigated the protective effects of SQ against cancer-induced skeletal muscle and adipose tissue wasting in CT26 tumor-bearing mice. Seven days after CT26 colon carcinoma implantation, BALB/c mice were orally administered SQ (150 or 300 mg/kg/day) or saline for 17 days. SQ supplementation significantly attenuated tumor-induced body weight loss and anorexia, along with a reduction in tumor weight in cachectic mice. Furthermore, SQ prevented the loss of muscle mass and fiber cross-sectional area, accompanied by enhanced grip strength. In the gastrocnemius muscle, SQ inhibited nuclear factor kappa B activation, thereby suppressing the expression of inflammatory cytokines while enhancing antioxidant enzyme expression. These effects collectively reduced protein degradation through the forkhead box O3a pathway and promoted protein synthesis and myogenesis via reactivation of phosphatidylinositol 3-kinase/Akt signaling. Molecular docking analysis further suggested that SQ potentially modulates PI3K activity by favorably occupying its regulatory pocket. In adipose tissue, SQ alleviated fat wasting by suppressing AMPK phosphorylation, leading to reduced lipolysis and fat browning and enhanced adipogenic/lipogenic gene expression. Overall, these findings demonstrate that SQ mitigates cancer-induced muscle and adipose tissue wasting through modulation of catabolic signaling pathways, highlighting its potential as a nutritional intervention for cancer cachexia.

Keywords:  adipose tissue wasting; cancer cachexia; muscle atrophy; squalene

DOI:  https://doi.org/10.1016/j.jnutbio.2026.110457
JPEN J Parenter Enteral Nutr. 2026 Jun 30.

Longitudinal changes of skeletal muscle mass and architecture in critically ill adults: A prospective matched cohort study.

Carolyn Tze Ing Loh, Zheng-Yii Lee, Nor'azim Mohd Yunos, Christian Stoppe, M Shahnaz Hasan.

   BACKGROUND: Skeletal muscle loss is a common consequence of critical illness, yet its determinants and prognostic significance remain unclear. This study investigated muscle trajectory during hospitalization in critically ill patients, factors predicting these changes, and the associations between early muscle changes with clinical and functional outcomes.
METHODS: Adults (≥18 years) with severe pneumonia requiring supplemental oxygen were enrolled within 72 h of ICU admission. Two groups were recruited: RT-PCR-confirmed COVID-19 and non-COVID pneumonia, individually matched by age (±10 years), sex, and ventilatory support. Ultrasound assessments of quadriceps muscles (quadriceps muscle layer thickness, rectus femoris cross-sectional area, pennation angle, fascicle length) and forearm muscle thickness were performed in the ICU on study Days 1, 7, and 14, at ICU discharge (if later), and at hospital discharge. Muscle trajectories were evaluated using linear mixed-effects models. Regression analyses examined associations of relative muscle changes with (1) potential predictors, (2) 60-day time-to-discharge alive, and (3) hospital discharge handgrip and knee extension strength.
RESULTS: Fifty-nine patients (29 COVID-19, 30 non-COVID) were analyzed. Quadriceps muscles changed significantly over time, while forearm muscle thickness did not; trajectories were comparable between groups. No patient characteristics, laboratory, or clinical factors were associated with muscle changes on Day 7 or hospital discharge. Day 7 muscle changes were not associated with time-to-discharge-alive at 60 days or muscle strength after baseline adjustment (all p > 0.05).
CONCLUSIONS: In critically ill patients, significant muscle changes occurred during hospitalization irrespective of COVID-19 status, but no predictors were identified. Early muscle change alone was not predictive of clinical or functional outcomes.
CLINICAL RELEVANCE STATEMENT: This study demonstrates that skeletal muscle changes significantly over the course of hospitalization with similar trajectories in COVID-19 and non-COVID patients, independent of patient characteristics or routine clinical and laboratory factors. Early muscle loss alone was not predictive of clinical and functional outcomes, highlighting the need for combined or alternative markers to better identify high-risk patients and guide targeted interventions in critical care.

Keywords:  COVID‐19; critical illness; intensive care unit; muscle strength; skeletal muscle

DOI:  https://doi.org/10.1002/jpen.70123
Proc Natl Acad Sci U S A. 2026 Jul 07. 123(27): e2609132123

A human lysosomal storage disorder toolkit for decoding proteome landscapes in cortical-like and dopaminergic-like induced neurons.

Felix Kraus, Yuchen He, Yizhi Jiang, Delong Li, Yohannes A Ambaw, Federico M Gasparoli, Joao A Paulo, Tobias C Walther, Robert V Farese, Steven P Gygi, Florian Wilfling, J Wade Harper.

  Lysosomes maintain cellular homeostasis by degrading proteins delivered via endocytosis and autophagy and by recycling building blocks for organelle biogenesis. Lysosomal storage disorders (LSDs) comprise a group of diseases affecting diverse lysosomal functions. To facilitate molecular phenotyping across diverse LSD gene classes, we are developing a library of human embryonic stem cells engineered to lack individual LSD genes as a resource for the field. Here, we report our initial stem cell toolkit lacking one of 23 LSD genes, including the majority of genes associated with sphingolipidoses and neuronal ceroid lipofuscinoses, and its use in the generation of a proteomic resource for induced cortical-like and midbrain dopaminergic-like neurons. In-depth abundance and correlation profiling across organelles and suborganelle components revealed potential vulnerabilities that reflect distinct patterns of proteome alterations across both genotypes and neuronal cell types. We characterize alterations in the mitochondrial proteome associated with GBA1 and ASAH1 deficiency and identify synaptic and mitochondrial defects in ASAH1-/- induced neurons that correlate with defects in neuronal firing rates. Moreover, we developed an informatic pipeline for proteome-wide identification of individual protein-protein interactions and protein complexes that may be disrupted as a result of LSD gene deficiency. Finally, we visualized structural alterations of ASAH1-deficient endolysosomes in situ using cryoelectron tomography, revealing swollen organelles that were largely devoid of dense internal membranes characteristic of wild-type cells, but containing numerous intralumenal vesicle compartments. This toolkit and associated proteomic landscapes provide a resource for defining molecular signatures associated with LSD gene dysfunction and organelle vulnerability.

Keywords:  iNeurons; lysosome; organelle; protein interactions; proteomics

DOI:  https://doi.org/10.1073/pnas.2609132123
J Endocrinol. 2026 Jun 29. pii: JOE-25-0367. [Epub ahead of print]

Chronic hyperinsulinemia accelerates adipose senescence via mitochondrial dysfunction and cGAS-STING signalling.

Astha Singh, Nilesh Khandelwal, Prashant Rai, Vinita Kushwaha, Sanchita Gupta, Ravi Kumar, Rishabh Mishra, Pradeep Tiwari, Raj Kumar Mishra, Sandeep Kumar Mathur, Anil Nilkanth Gaikwad.

  Prediabetes and Type 2 Diabetes represent major global health challenges and have escalated to pandemic levels. Adipose tissue functions as a critical endocrine organ, playing a central role in maintaining glucose homeostasis during fasting, feeding, and stress responses. In this study, we demonstrated that prolonged chronic hyperinsulinemic stress increases the burden of senescent adipocytes, accompanied by activation of the cGAS-STING signalling pathway. Chronic hyperinsulinemia-induced insulin-resistant 3T3-L1 and human mesenchymal stem cell-derived adipocytes exhibited elevated senescence-associated phenotypes, mitochondrial dysfunction and impaired cellular energetics. Notably, we found that mitochondrial DNA leakage triggered the cGAS-STING pathway in insulin-resistant adipocytes and mouse models. Temporal analysis revealed that mitochondrial dysfunction was detectable at earlier stages of chronic insulin exposure, preceding activation of the cGAS-STING pathway and senescence-associated markers, supporting a progressive model of cellular dysfunction. This phenomenon was also observed in adipose depots of individuals with Type 2 diabetes, underscoring the translational relevance of our findings. Targeting cGAS or STING, either pharmacologically or through genetic silencing, significantly reduced inflammatory and senescence-related features in hyperinsulinemia-induced insulin-resistant 3T3-L1 adipocytes. Furthermore, attenuation of senescence treatment with the combination of Dasatinib and Quercetin alleviated mitochondrial stress and associated adipose dysfunction. Collectively, our findings support a model in which prolonged hyperinsulinemic stress induces early mitochondrial dysfunction, followed by activation of cGAS-STING signalling and the subsequent emergence of adipocyte senescence-associated phenotypes, contributing to adipose tissue dysfunction in insulin resistance and Type 2 Diabetes.

Keywords:  Adipose tissue; Chronic hyperinsulinemia; Mitochondrial dysfunction; Senescence; cGAS-STING pathway

DOI:  https://doi.org/10.1530/JOE-25-0367
Hum Mol Genet. 2026 Jun 26. pii: ddag060. [Epub ahead of print]35(13):

Utrophin requires α-Syntrophin to maintain neuromuscular junction integrity in mdx mice.

Alissa Wierenga, Michelle Mendoza, Saad O Malik, Akash Agrawal, Aya Reda, Abigail Maag, Ameen Abou-Rjaily, Chenlang Gao, Mohammed Akaaboune.

  Dystrophin links the actin cytoskeleton to the extracellular matrix through the dystrophin-glycoprotein complex (DGC), providing structural stability to muscle fibers. In mdx mice, which lack dystrophin, neuromuscular junctions (NMJs) remain largely structurally and functionally intact despite extensive muscle pathology. Here, using single- and double-mutant mice deficient in dystrophin and α-syntrophin (α-syn), we investigated how utrophin upregulation contributes to NMJ maintenance in dystrophic muscle. During early postnatal development, when dystrophic muscles are transiently resistant to degeneration, the DGC proteins α-dystrobrevin, α-syn, and β-dystroglycan are broadly distributed along both synaptic and extra-synaptic regions of the sarcolemma, although their overall levels are reduced compared with wild-type (WT) muscle. In contrast, in WT mice, utrophin is restricted to NMJs, whereas in dystrophic muscles from both mutants, it is distributed along both synaptic and extra-synaptic regions of the sarcolemma, particularly within the innervated zone of muscle fibers. As muscles mature and degeneration begins, these DGC components become highly restricted to NMJs while being markedly reduced or absent from the extra-synaptic sarcolemma in many muscle cells. Although utrophin remains highly enriched at synaptic sites in mdx:α-syn-/- muscles, their NMJs display severe structural abnormalities compared with those of mdx mice. These include a dramatic reduction in synaptic fold depth and density, a decrease in presynaptic vesicle density, retraction of nerve terminals, and axonal thinning. These findings demonstrate that utrophin localization at the NMJ is not sufficient to preserve synaptic integrity and that functional interactions between utrophin and α-syn are required to maintain the NMJ in dystrophic muscle.

Keywords:  molecular genetics; mouse models; muscular dystrophy

DOI:  https://doi.org/10.1093/hmg/ddag060
Exp Mol Med. 2026 Jul 03.

Protein arginine methyltransferases coordinate mitochondrial stress adaptation and neuromuscular function.

Ju-Hyeon Bae, Chang-Lim You, Jeongmin Park, Jong-Sun Kang.

Sarcopenia and neuromuscular degeneration are key drivers of functional decline during ageing and arise not solely from muscle loss but also from failure of mitochondrial and metabolic stress adaptation across the neuromuscular system. Mitochondrial dysfunction, characterized by impaired oxidative phosphorylation, defective quality control and redox imbalance, contributes directly to muscle weakness, neuromuscular junction instability and motor unit degeneration. However, the upstream mechanisms governing the transition from adaptive remodelling to degenerative collapse remain incompletely defined. Protein arginine methyltransferases (PRMTs) have emerged as critical modulators of mitochondrial and metabolic stress signalling. Beyond epigenetic regulation, PRMTs influence signalling pathways that intersect with AMP-activated protein kinase (AMPK)-Forkhead box O (FOXO) and mechanistic target of rapamycin (mTOR), thereby regulating mitochondrial biogenesis, selective autophagy and mitophagy, proteostatic balance, and anabolic restraint. Distinct PRMT family members exert non-redundant functions across muscle fibres, satellite cells and motor neurons, collectively shaping neuromuscular stress resilience. We propose that PRMTs act as molecular rheostats that bias cellular responses to mitochondrial stress towards adaptive resolution or progression to neuromuscular degeneration, thereby positioning PRMT-regulated metabolic signalling as a unifying mechanism underlying sarcopenia and compromised healthspan.

DOI: https://doi.org/10.1038/s12276-026-01762-8
Bone Res. 2026 Jun 29. pii: 68. [Epub ahead of print]14(1):

Angiogenin mediates cell-cell fusion as a mitochondrial RNA processing enzyme.

Ke Shen, Yixiang Zeng, Jiekang Wang, Kangping Song, Surendra Kumar, Peisong Gao, Guo-Fu Hu, Xu Cao, Mei Wan.

Cell-cell fusion, essential for diverse physiological events, requires high ATP levels. While mitochondrial activity increases in fusing cells, the mechanism driving mitochondrial ribosome (mitoribosome) biogenesis to support these energy demands remains unclear. Here, we identify angiogenin (ANG) as a mitochondrial tRNA (mt-tRNA) processing enzyme critical for mitoribosome biogenesis during myoblast and osteoclast fusion. Upon fusion initiation, ANG translocates to mitochondria, promoting mitoribosome biogenesis to support translation of respiratory complex proteins for ATP production. Using transcriptome-wide PARE and 5' RACE analyses, we show that ANG cleaves the tRNA 3'-end in mitochondrial pre-RNA transcripts bordering rRNAs and mRNAs, enabling their release for translation. Loss of ANG or disruption of its ribonucleolytic activity impairs osteoclast and myoblast fusion, disrupting bone and muscle homeostasis and skeletal muscle regeneration post-injury. Our findings establish ANG as an essential mitoribosome biogenesis regulator and highlight a novel mechanism of mitochondria energy regulation in high-energy-demand biological processes.

DOI: https://doi.org/10.1038/s41413-026-00545-1
NPJ Aging. 2026 Jun 29.

Motor unit behavior adaptations across lifespan: sex differences in young, middle-aged and old adults.

Marco Carbonaro, Marta Boccardo, Clarissa M Brusco, Andrea M Pilotto, Rebecca Re, Fulvio Lauretani, Simone Porcelli, Martino V Franchi, Alberto Botter.

Aging is associated with neuromuscular decline, but how sex modulates motor unit adaptations across adulthood remains unclear. This study examined age- and sex-related differences in motor unit firing behavior in young (YG), middle-aged (MA), and older (OLD) adults by integrating high-density surface EMG decomposition with assessments of muscle morphology and daily physical activity. Linear mixed-effects models revealed significant effects of age and sex on mean firing rate: females showed higher rates than males at 30% maximal voluntary contraction (MVC) in YG and MA groups, but not in OLD, and no sex differences were observed at 50% MVC. Firing-rate variability was consistently higher in females. During force-increasing contractions, OLD adults showed reduced motor unit discharge modulation; in early-recruited units, reductions were significant in OLD females relative to both YG and MA females, while males showed reductions across both early- and late-recruited units. Males exhibited greater muscle thickness, cross-sectional area, and maximal torque, and daily physical activity was lower in OLD participants. These findings indicate that neuromuscular aging is associated with reduced discharge-rate modulation and a convergence of motor unit behavior between sexes in older age. Physical activity may contribute, underscoring the importance of sex-sensitive strategies to preserve neuromuscular function.

DOI: https://doi.org/10.1038/s41514-026-00427-0