bims-musmir 2025-10-19 papers

bims-musmir

Biomed News

on microRNAs in muscle

Issue of 2025–10–19
twelve papers selected by
Katarzyna Agnieszka Goljanek-Whysall, University of Galway

Gestational low-protein diet impairs mitochondrial function and skeletal muscle development by inducing immune responses in male offspring.
Response of UBR-box E3 ubiquitin ligases and protein quality control pathways to perturbations in protein synthesis and skeletal muscle size.
Revealing the Specific Contributions of Mitochondrial CB1 Receptors to the Overall Function of Skeletal Muscle in Mice.
Nicotinamide N-methyltransferase inhibition improves limb function in experimental peripheral artery disease.
POLRMT overexpression increases mtDNA transcription without affecting steady-state mRNA levels.
Lack of myotubularin phosphatase activity is the main cause of X-linked Myotubular Myopathy.
The mitochondrial side of frailty.
Protein Arginine N-Methyltransferase 4 Activation Contributes to Glucose-Induced Skeletal Muscle Atrophy.
Extreme physical inactivity alters iron metabolism: mechanisms and health issues for astronauts and bedridden patients.
Mitochondrial dysfunction alters early endosome trafficking via microtubule reorganization.
Pathogenesis of mtDNA point mutation m.10191T>C affecting complex I function is a multifactorial process leading to metabolic remodeling of mitochondria.
Patient-recorded indexing measurements (PRIMS) - study protocol of a prospective observational cohort study to improve the accuracy of the diagnosis of cancer cachexia.

Redox Biol. 2025 Oct 10. pii: S2213-2317(25)00403-3. [Epub ahead of print]87 103890

Gestational low-protein diet impairs mitochondrial function and skeletal muscle development by inducing immune responses in male offspring.

Atilla Emre Altinpinar, Moussira Alameddine, Ufuk Ersoy, Ioannis Kanakis, Vanja Pekovic-Vaughan, Susan E Ozanne, Katarzyna Goljanek-Whysall, Aphrodite Vasilaki.

  Maternal nutrition is essential for proper fetal and postnatal organ maturation and is linked to the future risk of developing metabolic syndrome, cardiovascular disease, and muscle loss. There is still limited understanding how a low-protein intake during gestation influences skeletal muscle development, inflammation, and the related pathways. This study aimed to investigate the impact of gestational low-protein diet in mice on skeletal muscle development and inflammatory responses in male offspring. Pups born from mothers fed a low-protein diet (LPD) were lactated by normal protein diet (NPD)-fed mothers and maintained on NPD post-weaning (LNN group). Offspring born from mothers fed an NPD and maintained on an NPD during lactation and beyond were used as controls (NNN group). In 21-day-old offspring from protein-restricted mothers, RNA-Seq analysis showed upregulation of immune response-related genes, enriching adaptive immunity pathways. Additionally, LNN group exhibited elevated markers of inflammation, along with disruptions in antioxidant defence balance and macrophages infiltration in gastrocnemius muscle at 3 months of age. Energy metabolism was impaired, as indicated by changes in related proteins and enzymes involved in mitochondrial function. We conclude that gestational LPD adversely affects skeletal muscle development in male offspring.

Keywords:  Immune response; Inflammation; Maternal nutrition; Oxidative stress; Protein restriction; Skeletal muscle

DOI:  https://doi.org/10.1016/j.redox.2025.103890
Am J Physiol Cell Physiol. 2025 Oct 13.

Response of UBR-box E3 ubiquitin ligases and protein quality control pathways to perturbations in protein synthesis and skeletal muscle size.

Leslie M Baehr, Luis Gustavo Oliveira de Sousa, Craig A Goodman, Adam P Sharples, David S Waddell, Sue C Bodine, David C Hughes.

  The N-degron pathway contributes to proteolysis by targeting N-terminal residues of destabilized proteins via E3 ligases that contain a UBR-box domain. Emerging evidence suggests the UBR-box family of E3 ubiquitin ligases (UBR1-7) are involved in the positive regulation of skeletal muscle mass. The purpose of this study was to explore the role of UBR-box E3 ubiquitin ligases under enhanced protein synthesis and skeletal muscle growth conditions. Cohorts of adult male mice were electroporated with constitutively active Akt (Akt-CA) or UBR5 RNAi constructs with a rapamycin diet intervention for 7 and 30 days, respectively. In addition, the UBR-box family was studied during the regrowth phase post nerve crush induced inactivity. Skeletal muscle growth with Akt-CA or regrowth following inactivity increased protein abundance of UBR1, UBR2, UBR4, UBR5 and UBR7. This occurred with corresponding increases in Akt-mTORC1/S6K and MAPK/p90RSK signaling and protein synthesis. The increases in UBR-box E3s, ubiquitination, and proteasomal activity occurred independently of mTORC1 activity and were associated with increases in markers related to autophagy, ER-stress, and protein quality control pathways. Finally, while UBR5 knockdown (KD) evokes atrophy, it occurs together with hyperactivation of mTORC1 and protein synthesis. In UBR5 KD muscles, we identified an increase in protein abundance for UBR2, UBR4 and UBR7, which may highlight a compensatory response to maintain proteome integrity. Future studies will seek to understand the role of UBR-box E3s towards protein quality control in skeletal muscle plasticity.

Keywords:  N-degron pathway; UBR5; hypertrophy; proteasome system; protein turnover

DOI:  https://doi.org/10.1152/ajpcell.00602.2025
Cells. 2025 Sep 28. pii: 1517. [Epub ahead of print]14(19):

Revealing the Specific Contributions of Mitochondrial CB1 Receptors to the Overall Function of Skeletal Muscle in Mice.

Zoltán Singlár, Péter Szentesi, Nyamkhuu Ganbat, Barnabás Horváth, László Juhász, Mónika Gönczi, Anikó Keller-Pintér, Attila Oláh, Zoltán Máté, Ferenc Erdélyi, László Csernoch, Mónika Sztretye.

  Skeletal muscle, constituting 40-50% of total body mass, is vital for mobility, posture, and systemic homeostasis. Muscle contraction heavily relies on ATP, primarily generated by mitochondrial oxidative phosphorylation. Mitochondria play a key role in decoding intracellular calcium signals. The endocannabinoid system (ECS), including CB1 receptors (CB1Rs), broadly influences physiological processes and, in muscles, regulates functions like energy metabolism, development, and repair. While plasma membrane CB1Rs (pCB1Rs) are well-established, a distinct mitochondrial CB1R (mtCB1R) population also exists in muscles, influencing mitochondrial oxidative activity and quality control. We investigated the role of mtCB1Rs in skeletal muscle physiology using a novel systemic mitochondrial CB1 deletion murine model. Our in vivo studies showed no changes in motor function, coordination, or grip strength in mtCB1 knockout mice. However, in vitro force measurements revealed significantly reduced specific force in both fast-twitch (EDL) and slow-twitch (SOL) muscles following mtCB1R ablation. Interestingly, knockout EDL muscles exhibited hypertrophy, suggesting a compensatory response to reduced force quality. Electron microscopy revealed significant mitochondrial morphological abnormalities, including enlargement and irregular shapes, correlating with these functional deficits. High-resolution respirometry further demonstrated impaired mitochondrial respiration, with reduced oxidative phosphorylation and electron transport system capacities in knockout mitochondria. Crucially, mitochondrial membrane potential dissipated faster in mtCB1 knockout muscle fibers, whilst mitochondrial calcium levels were higher at rest. These findings collectively establish that mtCB1Rs are critical for maintaining mitochondrial health and function, directly impacting muscle energy production and contractile performance. Our results provide new insights into ECS-mediated regulation of skeletal muscle function and open therapeutic opportunities for muscle disorders and aging.

Keywords:  ATP; calcium homeostasis; cannabinoid receptor type 1; mitochondria; mitochondrial cannabinoid receptor type 1; mtCB1 knockout; murine skeletal muscle; muscle force; skeletal endocannabinoid system

DOI:  https://doi.org/10.3390/cells14191517
Physiol Rep. 2025 Oct;13(20): e70615

Nicotinamide N-methyltransferase inhibition improves limb function in experimental peripheral artery disease.

Gengfu Dong, Jaewon Choi, Yufen Li, Diana C Muller, Zhuoxin Li, Yangyi E Luo, Terence E Ryan.

  Peripheral artery disease (PAD) impairs limb perfusion, walking ability, and increases the risk of amputation. Although current therapies reduce cardiovascular events, few interventions improve skeletal muscle function in PAD. Nicotinamide adenine dinucleotide (NAD+) metabolism is disrupted in PAD. Thus, it was hypothesized that inhibition of nicotinamide N-methyltransferase (NNMT), an enzyme that diverts precursors from the NAD+ salvage pathway, would improve ischemic limb function. We analyzed NAD+ pathway expression in gastrocnemius muscle from patients with and without PAD using RNA sequencing and proteomics datasets. Single-cell RNA sequencing data were used to assess NNMT expression in muscle stem cells (MuSCs) from BALB/cJ and C57BL/6J mice following hindlimb ischemia (HLI). Male BALB/cJ mice (n = 24) were randomized to either placebo or a NNMT inhibitor (NNMTi) delivered 3 h prior to HLI and daily thereafter. Functional assessments included laser Doppler perfusion imaging, muscle contractility, and a 6-min limb function test. Histological analyses were used to assess myofiber area and capillary density. NNMT mRNA and protein levels were significantly elevated in skeletal muscle from patients with PAD and were persistently elevated in MuSCs from BALB/cJ mice after HLI. NNMTi treatment did not affect limb perfusion recovery or capillary density but trended toward reduced necrosis severity (p = 0.08). Muscle mass and myofiber size were unchanged by treatment; however, NNMTi significantly improved muscle strength (p < 0.0001), power (p = 0.0305), and total work (p = 0.0367) in ischemic limbs compared to placebo. Inhibition of NNMT enhanced ischemic muscle strength and performance in a preclinical model of PAD independent of changes in perfusion.

Keywords:  ischemia; metabolism; skeletal muscle; vascular disease

DOI:  https://doi.org/10.14814/phy2.70615
Life Sci Alliance. 2025 Dec;pii: e202302563. [Epub ahead of print]8(12):

POLRMT overexpression increases mtDNA transcription without affecting steady-state mRNA levels.

Maria Miranda, Andrea Mesaros, Nathalie Scrima, Louise Pérard, Irina Kuznetsova, Martin Purrio, Ilian Atanassov, Aleksandra Filipovska, Arnaud Mourier, Nils-Göran Larsson, Inge Kühl.

POLRMT is the sole RNA polymerase in human mitochondria, where it generates primers for mitochondrial DNA (mtDNA) replication and transcribes the mtDNA to express genes encoding essential components of the oxidative phosphorylation (OXPHOS) system. Elevated POLRMT levels are found in several cancers and in mouse models with severe mitochondrial dysfunction. Here, we generated and characterized mice overexpressing Polrmt to investigate the physiological and molecular consequences of elevated POLRMT levels. Increasing POLRMT levels did not result in any pathological phenotype but led to increased exercise performance in male mice under stress conditions. Polrmt overexpression increased mtDNA transcription initiation, resulting in higher steady-state levels of the promoter-proximal L-strand transcript 7S RNA. Surprisingly, the abundance of mature mitochondrial RNAs was not affected by the elevated POLRMT levels. Furthermore, ubiquitous simultaneous overexpression of Polrmt and Lrpprc, which stabilizes mitochondrial messenger RNAs, did not increase steady-state levels of mitochondrial transcripts in the mouse. Our data show that POLRMT levels regulate transcription initiation, but additional regulatory steps downstream of transcription initiation and transcript stability limit OXPHOS biogenesis.

DOI: https://doi.org/10.26508/lsa.202302563
JCI Insight. 2025 Oct 14. pii: e189286. [Epub ahead of print]

Lack of myotubularin phosphatase activity is the main cause of X-linked Myotubular Myopathy.

Foteini Moschovaki-Filippidou, Christine Kretz, David Reiss, Gaetan Chicanne, Bernard Payrastre, Jocelyn Laporte.

  The MTM1 gene encodes myotubularin (MTM1), a phosphatidylinositol 3-phosphate (PI(3)P) lipid phosphatase. Loss-of-function mutations in MTM1 cause X-linked myotubular myopathy (XLMTM), a severe congenital myopathy with no available cure and a poorly understood pathomechanism. The importance of MTM1 enzymatic activity and its PI(3)P substrate in physiology under normal conditions and in XLMTM is unclear. We generated the Mtm1 KI C375S mice in which the endogenous MTM1 was converted to a phosphatase-dead protein. Mutant mice survived a median of 12 weeks and demonstrated progressively impaired motor skills. Observed muscle hypotrophy and reduced force production compared to their WT littermates (~3.9-fold reduction in absolute maximal force) were responsible for these severe phenotypes. A significantly higher level of PI(3)P was found in the muscle of Mtm1 KI C375S mice. Muscle histology and molecular characterization revealed XLMTM hallmarks, with alteration of the mTOR and autophagy pathways correlating with muscle hypotrophy, and abnormal myofiber intracellular organization correlating with impaired muscle force. Overall, this study reveals the importance of MTM1 phosphatase activity and related PI(3)P substrate for postnatal muscle maintenance, and highlights the significance of MTM1 phosphatase activity in the development of X-linked myotubular myopathy.

Keywords:  Genetics; Mitochondria; Mouse models; Muscle biology; Skeletal muscle

DOI:  https://doi.org/10.1172/jci.insight.189286
Curr Opin Clin Nutr Metab Care. 2025 Oct 06.

The mitochondrial side of frailty.

Emanuele Marzetti, Rosa Di Lorenzo, Anna Picca.

   PURPOSE OF REVIEW: Frailty, a prevalent geriatric condition marked by reduced physiological reserve and greater vulnerability to stressors, is increasingly linked to mitochondrial dysfunction. This review summarizes current evidence on mitochondrial quality control, bioenergetics, and signaling in frailty, with emphasis on biomarker discovery and translational potential.
RECENT FINDINGS: Preclinical and human studies have shown that impaired mitochondrial biogenesis, altered dynamics, and defective mitophagy contribute to frailty, sarcopenia, and immune dysregulation. Frail older adults exhibit reduced mitochondrial DNA content, diminished mitochondrial respiratory capacity, elevated reactive oxygen species generation, and distinctive metabolomic changes. Potential biomarkers include mitochondria-derived vesicles, circulating metabolites, and measures of peripheral blood mononuclear cell respiration, which may enable early detection of functional decline. Multivariate profiling approaches have identified sex-specific and shared molecular signatures converging on mitochondrial pathways. Interventions promoting mitochondrial health, including resistance training and targeted immunomodulation, hold promise in slowing frailty progression.
SUMMARY: Mitochondrial dysfunction lies at the intersection of musculoskeletal, metabolic, and immune changes underpinning frailty. While integrative biomarker panels have defined metabolic signatures, early diagnosis and personalized therapies remain unmet needs. Longitudinal studies are required to establish causality, refine biomarker utility, and guide precision medicine strategies to preserve mitochondrial function, extend healthspan, and improve quality of life in aging populations.

Keywords:  inflammaging; metabolic dysregulation; mitochondrial quality control; oxidative capacity; physical frailty

DOI:  https://doi.org/10.1097/MCO.0000000000001175
FASEB J. 2025 Oct 31. 39(20): e71135

Protein Arginine N-Methyltransferase 4 Activation Contributes to Glucose-Induced Skeletal Muscle Atrophy.

Pawan Kumar, Farah Gulzar, Nikita Chhikara, Arvind K Maurya, Sushmita Singh, Ishbal Ahmad, Sanjeev Kanojiya, Akhilesh K Tamrakar.

  Protein arginine N-methyltransferase 4 (PRMT4; also known as Coactivator-Associated Arginine Methyltransferase 1/CARM1) plays a crucial role in cell-type-specific biological processes. In skeletal muscle, PRMT4 has been demonstrated to manage plasticity by regulating skeletal muscle development, regeneration, and glycogen metabolism. However, its impact on skeletal muscle metabolic homeostasis under pathologic conditions remains obscure. Here, we investigated the role of PRMT4 in skeletal muscle atrophy under diabetes. In L6 myotubes, high glucose exposure increased mRNA expression and protein level of PRMT4, correlating with the induction of atrophy features. Notably, the pharmacological inhibition or small interfering RNA (siRNA)-mediated downregulation of PRMT4 suppressed high glucose-induced atrophy features. The high glucose exposure elevated asymmetric dimethylarginine (ADMA) via PRMT4 activation, disrupting insulin signaling in L6 myotubes. Further, we have established the activation of the ubiquitin-proteasome-mediated protein degradation pathway in the high glucose-induced skeletal muscle atrophy program via PRMT4, without any significant effect on the autophagy pathway. Additionally, we have demonstrated that proteasome-mediated protein degradation released free amino acids that triggered mammalian target of rapamycin (mTOR) signaling in a PRMT4-dependent manner. Altogether, our findings establish PRMT4 as a critical regulator of glucose-induced skeletal muscle atrophy and propose it as a potential therapeutic target for the management of diabetes-associated skeletal muscle atrophy.

Keywords:  PRMT4; arginine methylation; post translational modification; skeletal muscle atrophy

DOI:  https://doi.org/10.1096/fj.202502570R
J Physiol. 2025 Oct 16.

Extreme physical inactivity alters iron metabolism: mechanisms and health issues for astronauts and bedridden patients.

Mathieu Horeau, Maelys Auffret, Olivier Loréal, Frédéric Derbré.

  Iron is a biologically indispensable yet potentially harmful element: essential for numerous metabolic processes but toxic in excess, potentially leading to organ damage. Under conditions of extreme physical inactivity, such as microgravity or prolonged bed-rest, physical deconditioning occurs, adversely affecting functional capacities and health. Anaemia and muscle atrophy may contribute to systemic iron redistribution, as red blood cells and skeletal muscle collectively concentrate most body iron. Here we summarize a decade of research conducted in rodent and human ground-based models to investigate how extreme physical inactivity alters systemic and cellular iron homeostasis, and explore the underlying mechanisms. During the first days an increase in plasma iron availability occurs in both men and premenopausal women, likely due to accelerated erythrophagocytosis in spleen and redistribution of iron from degraded erythrocytes. Despite the rapid onset of muscle fibre atrophy under these conditions, skeletal muscle appears to accumulate iron rather than release it and therefore may not necessarily contribute to the systemic redistribution of iron. Increased circulating hepcidin levels observed during this early phase could contribute to both redistribution and tissue iron sequestration. After several weeks of exposure plasma iron availability remains elevated in men exposed to extreme physical inactivity, potentially exposing to chronic tissue iron accumulation. In contrast a return to baseline seems to occur in premenopausal women. These findings point to a broad and persistent redistribution of iron metabolism in men in response to extreme physical inactivity. However the long-term effects on iron metabolism in women remain poorly understood and warrant further investigation.

Keywords:  disuse; haemoglobin; skeletal muscle; spaceflight; trace elements

DOI:  https://doi.org/10.1113/JP289149
Life Sci Alliance. 2026 Jan;pii: e202403020. [Epub ahead of print]9(1):

Mitochondrial dysfunction alters early endosome trafficking via microtubule reorganization.

Anjali Vishwakarma, Lilia Chihki, Kiran Todkar, Mathieu Ouellet, Marc Germain.

Mitochondria are essential for bioenergetics and cellular processes including cell differentiation and immunity; alterations in these processes cause a wide range of muscular and neurological pathologies. Although these pathologies have traditionally been associated with ATP deficits, mitochondrial dysfunction also leads to reactive oxygen species (ROS) generation, inflammation, and alterations in the function of other organelles. Although the negative impact of mitochondrial dysfunction on lysosomal activity is established, the relationship between mitochondria and the rest of the endocytic compartment remains poorly understood. Here, we show that inhibiting mitochondrial activity through genetic and chemical approaches causes early endosome (EE) perinuclear aggregation and impairs cargo delivery to lysosomes. This impairment is due to ROS-mediated alterations in microtubule architecture and centrosome dynamics. Antioxidants can rescue these EE defects, underlying the pivotal role of mitochondria in maintaining cellular activities through ROS regulation of microtubule networks. Our findings highlight the significance of mitochondria beyond ATP production, emphasizing their critical involvement in endocytic trafficking and cellular homeostasis. These insights emphasize mitochondria's critical involvement in cellular activities and suggest novel targets for therapies to mitigate the effects of mitochondrial dysfunction.

DOI: https://doi.org/10.26508/lsa.202403020
Biochim Biophys Acta Mol Basis Dis. 2025 Oct 10. pii: S0925-4439(25)00418-1. [Epub ahead of print]1872(2): 168070

Pathogenesis of mtDNA point mutation m.10191T>C affecting complex I function is a multifactorial process leading to metabolic remodeling of mitochondria.

Zeinab Alsadat Ahmadi, Alfredo Cabrera-Orefice, Marta Zaninello, Esther Barth, Matteo Veronese, Richard Rodenburg, Elena I Rugarli, Susanne Brodesser, Susanne Arnold, Ulrich Brandt.

  Inherited mitochondrial disorders are of multiple genetic origins and may lead to a broad range of frequently severe disease phenotypes. Yet, how molecular causes ultimately present as a clinical phenotype is poorly understood. To address this conundrum starting from the molecular defect, we thoroughly investigated the consequences of the well-known pathogenic mitochondrial DNA mutation m.10191T>C. The mutation changes serine-45 in subunit ND3 of respiratory chain complex I to proline and causes Leigh syndrome, which is one of the most devastating mitochondrial diseases. Human mitochondria carrying the mutation ND3S45P retained 30-40 % of complex I activity and oxidative phosphorylation capacity. In stark contrast, intact mutant cells exhibited only minimal oxygen consumption and a massively increased NADH/NAD+ ratio. Since the energy barrier for the Active/Deactive transition of complex I was reduced by ∼20 kJ∙mol-1 in mutant cells, we concluded that complex I was shut-off by malfunctioning of an as yet unknown regulatory pathway. Comprehensive analysis of the mitochondrial complexome of cybrids, patient fibroblasts and muscle biopsies rendered other causes for the accumulation of NADH unlikely. The complexome datasets provide a rich resource for further studies to discover possible additional factors involved in regulating complex I. We propose that the derailed regulation of complex I is the main culprit leading to NADH accumulation and eventually the severity of the disease phenotype caused by mutation ND3S45P.

Keywords:  Active/deactive transition; Complex I; Complexome profiling; Mitochondria; Mitochondrial disease; mtDNA

DOI:  https://doi.org/10.1016/j.bbadis.2025.168070
BMC Cancer. 2025 Oct 14. 25(1): 1572

Patient-recorded indexing measurements (PRIMS) - study protocol of a prospective observational cohort study to improve the accuracy of the diagnosis of cancer cachexia.

N D Hildebrand, M A T Sier, S M J van Kuijk, L S M Hoeijmakers, L L G C Ackermans, J Ubachs, L Stassen, N F M Ruber, V Schaghen-D'Antonio, E P Goedegebuure, L Baade-Corpelijn, B C Bongers, J Stoot, M Sosef, S Lambrechts, P J de Vos van Steenwijk, M Engelen, T Lubbers, T J Blokhuis, J A Ten Bosch, L Valkenburg-van Iersel, J de Vos-Geelen, M den Dulk, D P J van Dijk, S W M Olde Damink, S S M Rensen.

   BACKGROUND: Cachexia is a major challenge throughout cancer treatment. Unintentional weight loss, the principal diagnostic criterium of cancer cachexia, is usually assessed through self-reported body weight change, which may be prone to bias. Other aspects of cancer cachexia include altered body composition (e.g., loss of muscle mass) and impaired physical activity. The central aim of the 'Patient-Recorded Indexing MeasurementS' (PRIMS) study is to improve the accuracy of the diagnosis of cachexia in patients with cancer. The primary objectives are to compare self-reported and objectively measured pre-treatment weight changes, and to assess their respective association with treatment-related adverse events and survival. Secondary objectives are to define host phenotypes based on combinations of objectively assessed cachexia-related data that are predictive of treatment-related adverse events and survival, and to investigate longitudinal associations between body weight and physical activity patterns.
METHODS: This prospective observational cohort study will be conducted in two Dutch referral centers specialized in treatment of patients with upper gastrointestinal, hepatobiliary, pancreatic, colorectal, and ovarian cancer. We will include 300 cancer patients scheduled for either neoadjuvant chemo(radio)therapy or upfront elective surgery. Patients will undergo a baseline assessment consisting of nutritional screening (anthropometry, body weight assessment), body composition analysis, and physical fitness tests. Patients will be provided with an accelerometer and weight scale for continuous/daily at-home measurements before, throughout, and after treatment. Treatment-related adverse events will be assessed according to the Common Terminology Criteria for Adverse Events or Clavien-Dindo classification. Response to chemo(radio)therapy will be assessed according to 'Response Evaluation Criteria in Solid Tumors' (RECIST) criteria. Disease-free and overall survival will be recorded. Relationships between cachexia-related parameters and outcomes will be investigated using multivariable logistic regression analysis.
DISCUSSION: The PRIMS protocol comprises a core assessment set of objective measurements to improve the diagnosis of cancer cachexia. It will help to identify patient phenotypes associated with treatment-related adverse events and survival. This approach is expected to advance cachexia diagnostics and enhance future clinical and translational research on the prevalence, severity, and impact of cancer cachexia. PRIMS will also aid clinicians in providing personalized counseling on treatment options and their expected outcomes.
TRIAL REGISTRATION: Medical Ethics Committee of the Academic Hospital Maastricht/Maastricht University (azM/UM) (METC18012, version 4.0, June 2024), Netherlands Trial Register (NL65402.068.18). The trial is registered in the ClinicalTrials.gov register (NCT05899205).

Keywords:  Body weight change; Cancer cachexia; Physical activity; Physical fitness

DOI:  https://doi.org/10.1186/s12885-025-14979-z