bims-musmir 2026-08-16 papers

bims-musmir

Biomed News

on microRNAs in muscle

Issue of 2026–08–16
seven papers selected by
Katarzyna Agnieszka Goljanek-Whysall, University of Galway

Circulating granulocyte colony-stimulating factor as a sex-unbiased global marker of lung and colorectal cancer cachexia pre-clinical models.
Temporal multi-omic analysis uncovers sex-biased molecular programs underlying skeletal muscle adaptation to endurance training.
Comprehensive transcriptomic profiling reveals impaired polyamine metabolism as a contributor to age-related muscle decline.
Extracellular vesicles derived from immobilization-induced atrophic muscle of male mice contain distinct microRNA profiles and impact mRNA profiles in brain neurons.
Bone Loss, Osteoporosis, and Skeletal Fragility: Hidden Consequences of Cancer Cachexia.
A semi-automated pipeline for morphological analysis of myonuclei along single muscle fibers.
Mitochondrial stress activates ELT-2-dependent lysosomal proteostasis to extend lifespan in C. elegans.

Exp Physiol. 2026 Aug 13.

Circulating granulocyte colony-stimulating factor as a sex-unbiased global marker of lung and colorectal cancer cachexia pre-clinical models.

Francielly Morena, Eleanor R Schrems, Ana Regina Cabrera, Ruqaiza Muhyudin, Sepideh Shakeri, Stavroula Tsitkanou, Mark Viggars, Tyrone A Washington, Nicholas P Greene.

  Cancer cachexia, affecting up to 80% of patients with advanced cancer, is characterized by metabolic and inflammatory dysregulation driven by tumour- and host-derived factors. Although cytokines are central to cachexia pathogenesis, their circulating profiles and transcriptional relevance across models and sexes remain incompletely defined. We characterized plasma cytokines and skeletal muscle inflammatory signatures in multiple cachexia models, including Lewis Lung Carcinoma (LLC), Colon-26 (C26) and ApcMin/+ mice. Animals were monitored for 4 weeks (LLC), 25 days (C26) or until ∼20 weeks of age (ApcMin/+) per model appropriate endpoints. Publicly available RNA-sequencing datasets from gastrocnemius (LLC) and tibialis anterior (C26 and ApcMin/+) muscles were integrated with plasma profiling using a Mouse Cytokine/Chemokine 32-Plex assay. To enhance accessibility and reproducibility, we developed an interactive Shiny application - thecachexiatlas/Cytokine Explorer - enabling dynamic visualization of cytokine levels, transcriptional signatures and phenotype correlations across models and sexes. Cytokine receptor encoding genes (Il6ra, Il4ra, Csf3, Osmr) and inflammatory pathways were consistently enriched in skeletal muscle of cachectic animals across models and sexes. Among circulating cytokines, granulocyte colony-stimulating factor (G-CSF) was uniquely elevated in all models and both sexes. Elevated G-CSF levels exhibited stronger negative correlations with tibialis anterior muscle mass than the commonly used cytokine interleukin (IL)-6, particularly when expressed as the ratio of G-CSF to the anti-inflammatory cytokine IL-13. The G-CSF:IL-13 ratio may represent a robust global biomarker of cachexia severity. The Cytokine Explorer Shiny app provides an open, interactive platform to facilitate hypothesis generation and advance research in cancer cachexia.

Keywords:  RNA sequencing; atrophy; cancer cachexia; chemokine; cytokine; inflammation; skeletal muscle

DOI:  https://doi.org/10.1113/EP093809
Cell Rep. 2026 Aug 12. pii: S2211-1247(26)00901-0. [Epub ahead of print]45(8): 117823

Temporal multi-omic analysis uncovers sex-biased molecular programs underlying skeletal muscle adaptation to endurance training.

MoTrPAC study group

  Exercise training confers broad health benefits, yet molecular regulators of skeletal muscle adaptation, particularly sex-specific mechanisms, remain incompletely understood. Integrating new and previously published multi-omics data from the molecular transducers of physical activity consortium (MoTrPAC), we characterized metabolomic, epigenomic, transcriptomic, proteomic, and post-translational modification (PTM) responses to 1-8 weeks of endurance exercise training in male and female rat gastrocnemius. While transcriptomic and proteomic responses were largely sex-concordant, there were distinct sex-specific training-induced PTM signatures, particularly in the redox proteome. Females exhibited decreased mitochondrial protein cysteine oxidation alongside increased oxidation of glycolytic proteins relative to males, suggesting sex-biased subcellular reactive oxygen species (ROS) dynamics. Multi-omic factor analysis (MOFA) identified coordinated sex-concordant molecular programs and further supported female-specific mechanisms of redox buffering with training. Together, these findings indicate that sex-specific skeletal muscle exercise adaptations are particularly evident at the PTM level in rats, and identify future avenues for precision exercise health and medicine.

Keywords:  CP: Metabolism; PTMs; cysteine oxidation; endurance exercise; exercise training; mitochondrial remodeling; multi-omics; post-translational modifications; sex differences; skeletal muscle, proteomics

DOI:  https://doi.org/10.1016/j.celrep.2026.117823
iScience. 2026 Aug 21. 29(8): 117000

Comprehensive transcriptomic profiling reveals impaired polyamine metabolism as a contributor to age-related muscle decline.

Veronica Ruggieri, Andrea Bracaglia, Lorenza Esposito, Nicola Tumino, Piera Filomena Fiore, Sofia Botta, Alberto Macone, Jessica Ohana, Marina Bouchè, Lucia Latella, Lorenzo Giordani, Luca Madaro.

  Sarcopenia, the age-related decline in skeletal muscle mass and function, profoundly affects skeletal muscle structure and performance. We present a spatial transcriptomic atlas of skeletal muscle from young and aged mice, resolving transcriptional reprogramming across fiber types and tissue compartments. Our analyses reveal alterations in sarcomeric organization, excitation-contraction coupling, oxidative stress responses, and fiber type-specific metabolic rewiring. Conserved molecular signatures across muscles and species highlight Car3 as a potential biomarker of sarcopenia. We also uncover a selective downregulation of polyamine biosynthetic enzymes, leading to reduced spermidine levels in aged muscle. This decline affects muscle-resident populations, as limiting polyamine metabolic flux in both murine and human fibro-adipogenic progenitors (hFAPs) induces aging-like features, including myofibroblast differentiation, extracellular matrix dysregulation, and impaired ability to support myogenesis. Together, our findings reveal spatially organized, fiber type-specific, and polyamine-linked mechanisms of muscle aging and position the polyamine pathway as a promising therapeutic target.

Keywords:  Amd1; fibro-adipogenic progenitors; polyamines; sarcopenia; spatial transcriptomics

DOI:  https://doi.org/10.1016/j.isci.2026.117000
Physiol Rep. 2026 Aug;14(16): e71052

Extracellular vesicles derived from immobilization-induced atrophic muscle of male mice contain distinct microRNA profiles and impact mRNA profiles in brain neurons.

Noriaki Kawanishi, Shuichi Machida, Katsuhiko Suzuki.

  Muscle atrophy caused by inactivity leads to declines in multiple physiological functions, including brain function. Although skeletal muscle is known to secrete extracellular vesicles (EVs) such as exosomes, how inactivity-induced muscle atrophy alters the properties and functions of these EVs remains unclear. In this study, we investigated the effects of cast immobilization-induced muscle atrophy on the microRNA (miRNA) profiles of skeletal muscle-derived EVs in mice, as well as their impact on transcriptome changes in brain neurons. Muscle atrophy induced by cast immobilization significantly altered the microRNA profiles of skeletal muscle-derived EVs, with 25 microRNAs upregulated and 2 microRNAs downregulated compared with controls. Moreover, treatment of brain neurons with EVs derived from atrophic skeletal muscle markedly changed neuronal mRNA expression profiles. Gene Ontology (GO) analysis revealed that upregulated mRNAs in EV-treated neurons were enriched in genes involved in the positive regulation of programmed cell death, including apoptosis. Consistently, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated activation of apoptosis-related signaling pathways in brain neurons. These findings suggest that muscle atrophy-induced alterations in skeletal muscle-derived EVs may contribute to brain dysfunction by promoting apoptotic processes in brain neurons.

Keywords:  brain neurons; exosomes; extracellular vesicles; microRNA; muscle atrophy

DOI:  https://doi.org/10.14814/phy2.71052
Cells. 2026 Aug 01. pii: 1397. [Epub ahead of print]15(15):

Bone Loss, Osteoporosis, and Skeletal Fragility: Hidden Consequences of Cancer Cachexia.

Kyle H Richardson, Jessica E Parker, Fabrizio Pin.

  Cancer cachexia (CC) is a devastating, multi-organ syndrome historically defined by the progressive wasting of skeletal muscle and adipose tissue. However, emerging evidence suggests that the skeletal system is also a major, yet underappreciated target of this catabolic state. While bone loss in oncology is primarily attributed to skeletal metastasis or cancer treatment-induced bone loss (CTIBL), clinical and preclinical data has increasingly demonstrated that tumor and host-derived systemic signals can drive severe bone deterioration even in non-metastatic disease. This review synthesizes current information available on bone loss, osteopenia, and skeletal decline in the context of CC, with a specific focus on non-metastatic disease. By examining the available literature, we argue that bone loss is a "hidden" yet fundamental systemic manifestation of the cachectic state. Furthermore, we aim to highlight how concurrent muscle and bone deterioration (osteosarcopenia) dramatically worsens prognosis in several different cancers in both the adult and pediatric populations. Ultimately, this review highlights the potential contribution of cancer cachexia to osteoporosis and skeletal fragility, supporting the need for greater clinical awareness, improved musculoskeletal screening, and the development of targeted therapeutic strategies.

Keywords:  BMD; bone loss; cancer cachexia; fracture risk; osteoporosis

DOI:  https://doi.org/10.3390/cells15151397
iScience. 2026 Aug 21. 29(8): 116961

A semi-automated pipeline for morphological analysis of myonuclei along single muscle fibers.

Esben T Schroeder, Helia G Megowan, Madeline Luu, Adam Shuaib, Adam C Fries, Jake Searcy, Hans C Dreyer.

  Manual quantitation of skeletal muscle myonuclear number, spatial orientation, and morphology is time-consuming and subject to error and bias. To overcome these limitations, we developed and validated a semi-automated, quantitative, and reproducible image-analysis pipeline. The workflow combines FIJI-based preprocessing with custom Python scripts to process immunohistological images of individual muscle fibers, enabling high resolution and scalable quantification of nuclei. The analyses incorporate morphometric parameters including nuclear position, shape, and three-dimensional orientation, as well as centroid-to-skeleton distance and nearest-neighbor relationships to capture spatial patterns of myonuclear organization along the fiber. Outputs include per-fiber and biopsy-level summaries integrated with IMARIS metrics. This semi-automated approach provides a robust and efficient platform for high-throughput analysis of myonuclear number and structural features across large single fiber datasets.

Keywords:  ImageJ; automation; muscle; pipeline

DOI:  https://doi.org/10.1016/j.isci.2026.116961
Sci Adv. 2026 Aug 14. 12(33): eaeh0657

Mitochondrial stress activates ELT-2-dependent lysosomal proteostasis to extend lifespan in C. elegans.

Rendan Yang, Yu Sun, Wenzheng Wang, Yuxuan Lei, Lin Chen, Xiaoxu Li, Raya B Liu, Ang Zhou, Arwen W Gao, Liangshan Mu, Johan Auwerx, Terytty Yang Li.

Mild mitochondrial stress could extend lifespan across species, yet the underlying mechanism remains unclear. Here, we show that inhibition of mitochondrial respiration induces a sustained transcriptional program that enhances lysosomal proteolysis during aging in Caenorhabditis elegans. Mechanistically, this response is primarily regulated by the intestinal GATA transcription factor ELT-2, which retains high expression and directly binds to GATA motifs in the promoters of lysosomal protease genes to promote their transcriptional activation. Moreover, we identified R249 within the conserved zinc-finger DNA binding domain of ELT-2 as a key residue required for its transcriptional activity. Notably, this mitochondrion-ELT-2-lysosome axis operates largely independently of the mitochondrial unfolded protein response (UPRmt) to counteract aging. Furthermore, increased lysosomal activity, as well as the lysosomal proteases CPR-5 and CPR-8, is essential for mitochondrial stress-induced clearance of toxic polyglutamine (polyQ) aggregates and lifespan extension. Together, our findings reveal a previously unrecognized ELT-2-dependent lysosomal proteostasis pathway that acts downstream of mitochondrial stress to maintain protein homeostasis and promote longevity.

DOI: https://doi.org/10.1126/sciadv.aeh0657