bims-musmir 2025-03-02 papers

bims-musmir

Biomed News

on microRNAs in muscle

Issue of 2025–03–02
eleven papers selected by
Katarzyna Agnieszka Goljanek-Whysall, University of Galway

Identification of a senescence-associated transcriptional program in skeletal muscle of cachectic pancreatic-tumor bearing mice.
Resistance exercise training in older men reduces ATF4-activated and senescence-associated mRNAs in skeletal muscle.
Dietary nitrate supplementation mitigates age-related changes at the neuromuscular junction in mice.
Withaferin A Attenuates Muscle Cachexia Induced by Angiotensin II Through Regulating Pathways Activated by Angiotensin II.
Alterations of PINK1-PRKN signaling in mice during normal aging.
ActRII or BMPR ligands inhibit skeletal myoblast differentiation, and BMPs promote heterotopic ossification in skeletal muscles in mice.
MARIGOLD and MitoCIAO, two searchable compendia to visualize and functionalize protein complexes during mitochondrial remodeling.
Low-Carbohydrate Diet Exacerbates Denervation-Induced Atrophy of Rat Skeletal Muscle Under the Condition of Identical Protein Intake.
Advancements in genetic research and RNA therapy strategies for amyotrophic lateral sclerosis (ALS): current progress and future prospects.
Oleuropein supplementation increases resting skeletal muscle fractional PDH activity but does not influence whole-body metabolism: A randomized, double-blind, placebo-controlled trial in healthy, older males.
The effect of pre-existing sarcopenia on outcomes of critically ill patients treated for COVID-19.

Am J Physiol Cell Physiol. 2025 Feb 24.

Identification of a senescence-associated transcriptional program in skeletal muscle of cachectic pancreatic-tumor bearing mice.

Jeremy B Ducharme, Madison E Carelock, Martin M Schonk, Nour M Al-Zaeed, Weizhou Zhang, Sarah M Judge, Andrew R Judge.

  Cancer cachexia is the involuntary loss of body and skeletal muscle mass, which negatively impacts physical function, quality of life, treatment tolerance, and survival. Skeletal muscles of cachectic people and mice with pancreatic tumors also exhibit skeletal muscle damage, non-resolute immune cell infiltration, and impaired regeneration. These phenotypes may be influenced by the accumulation of senescent cells, which secrete factors detrimental to skeletal muscle health. However, there is currently no comprehensive research on senescent cell accumulation in skeletal muscle of tumor-bearing hosts, with or without chemotherapy. To address this gap, we cross-referenced the SenMayo panel of 125 senescence-related genes with our RNA-seq dataset in mouse skeletal muscle during the initiation and progression of cancer cachexia, which revealed a differential expression of 39 genes at pre-cachexia, 64 genes at cachexia onset, and 72 genes when cachexia is severe. Since p16 is a canonical marker of senescence, we subsequently orthotopically injected p16-tdTomato reporter mice with murine KPC pancreatic cancer cells and treated a subset of mice with chemotherapy. At experimental endpoint, when KPC treatment-naïve mice were cachectic, we observed an increased accumulation of p16+ cells, along with increased mRNA levels of hallmark senescence markers (Cdkn1a/p21, Cdkn2a/p16, Glb1/senescent-associated-β-galactosidase), which were exacerbated by chemotherapy. Lastly, we demonstrate an increase in CDKN1A/p21 in the muscle of cachectic patients with pancreatic cancer, which associated with cachexia severity. These findings suggest that senescent cells accumulate in skeletal muscle of cachectic pancreatic tumor-bearing hosts and that chemotherapy can exacerbate this accumulation.

Keywords:  Cachexia; Cellular Senescence; Glb1; p16; p21

DOI:  https://doi.org/10.1152/ajpcell.00816.2024
Geroscience. 2025 Feb 27.

Resistance exercise training in older men reduces ATF4-activated and senescence-associated mRNAs in skeletal muscle.

Zachary D Von Ruff, Matthew J Miller, Tatiana Moro, Paul T Reidy, Scott M Ebert, Elena Volpi, Christopher M Adams, Blake B Rasmussen.

  Sarcopenia increases the risk of frailty, morbidity, and mortality in older adults. Resistance exercise training improves muscle size and function; however, the response to exercise training is variable in older adults. The objective of our study was to determine both the age-independent and age-dependent changes to the transcriptome following progressive resistance exercise training. Skeletal muscle biopsies were obtained before and after 12 weeks of resistance exercise training in 8 young (24 ± 3.3 years) and 10 older (72 ± 4.9 years) men. RNA was extracted from each biopsy and prepared for analysis via RNA sequencing. We performed differential mRNA expression, gene ontology, and gene set enrichment analyses. We report that when comparing post-training vs pre-training 226 mRNAs and 959 mRNAs were differentially expressed in the skeletal muscle of young and older men, respectively. Additionally, 94 mRNAs increased, and 17 mRNAs decreased in both young and old, indicating limited overlap in response to resistance exercise training. Furthermore, the differential gene expression was larger in older skeletal muscle. Finally, we report three novel findings: 1) resistance exercise training decreased the abundance of ATF4-activated and senescence-associated skeletal muscle mRNAs in older men; 2) resistance exercise-induced increases in lean mass correlate with increased mRNAs encoding mitochondrial proteins; and 3) increases in muscle strength following resistance exercise positively correlate with increased mRNAs involved in translation, rRNA processing, and polyamine metabolism. We conclude that resistance exercise training elicits a differential gene expression response in young and old skeletal muscle, including reduced ATF-4 activated and senescence-associated gene expression.

Keywords:  ATF4; Aging; Resistance exercise; Senescence; Skeletal muscle

DOI:  https://doi.org/10.1007/s11357-025-01564-2
J Physiol. 2025 Feb 26.

Dietary nitrate supplementation mitigates age-related changes at the neuromuscular junction in mice.

Maira Rossi, Lucrezia Zuccarelli, Lorenza Brocca, Cristiana Sazzi, Clarissa Gissi, Paola Rossi, Bruno Grassi, Simone Porcelli, Roberto Bottinelli, Maria Antonietta Pellegrino.

  In ageing, denervation and neuromuscular junction (NMJ) instability occur alongside mitochondrial alterations and redox unbalance, potentially playing a significant role in the process. Moreover, the synthetic pathway was shown to be critical for proper innervation and NMJ stability. Nitric oxide (NO) modulates redox status, mitochondrial function and the synthetic pathway. Its bioavailability declines with age. We hypothesize that nitrate supplementation could counteract age-related neuromuscular alterations. We compared young (Y) (7 months old), old (O) (24 months old) and old mice supplemented daily with 1.5 mm inorganic NaNO3 dissolved in drinking water for 8 weeks (ON) (24 months old). Compared to Y, O mice displayed impaired NO signalling and transport (lower phosphorylated-neuronal NO synthase and sialin content); greater nitrosative and oxidative stress (higher 3-nitrotyrosine levels and protein carbonylation); lower glutathione peroxidase (GPX antioxidant enzyme); smaller muscle fibres; and larger muscle fibrosis. NMJ integrity was impaired, exhibiting age-related alterations such as larger fragmentation, lower overlap, larger endplate areas and lower compactness. Consistently, greater expression of denervation-associated markers (Gadd45α, MyoG, RUNX1, AChRγ and NCAM1) and higher NCAM1+ fibres percentage suggested denervation. Importantly, mitochondrial content, dynamics and function were unchanged. Compared to O, ON mice showed improved NO bioavailability in muscle (higher nitrate-nitrite concentration); lower fibrosis and improved muscle fibre size; higher phosphorylation of P70S6K and S6, downstream factors of Akt/mammalian target of rapamycin synthetic pathway; lower oxidative stress (lower carbonylated proteins and mitochondrial hydrogen peroxide production, higher GPX protein levels); reverted age-related alterations of NMJ morphology; and lower percentage of NCAM1+ fibres. Nitrate supplementation could be a therapeutic strategy to counteract muscle decline with ageing. KEY POINTS: Ageing leads to instability at the neuromuscular junction (NMJ), which is crucial for muscle size and function, ultimately giving rise to denervation and muscle fibres loss. Mitochondrial function, redox status and activation of synthetic pathway are critical processes for proper muscle innervation and stability of the NMJ. Nitric oxide was shown to modulate intracellular processes involved in NMJ stability such as balance of reactive oxygen species, mitochondrial function and protein synthesis. Its bioavailability decreases with ageing. Our study shows that nitrate supplementation in old mice improved redox balance, enhanced the anabolic pathway and stabilized nerve-muscle interactions, suggesting a potential strategy to mitigate the neuromuscular decline associated with ageing.

Keywords:  ageing; extensor digitorum longus; gastrocnemius; mitochondria; neuromuscular junction; nitrate supplementation; oxidative stress; tibialis anterior

DOI:  https://doi.org/10.1113/JP287592
Cells. 2025 Feb 08. pii: 244. [Epub ahead of print]14(4):

Withaferin A Attenuates Muscle Cachexia Induced by Angiotensin II Through Regulating Pathways Activated by Angiotensin II.

Sham S Kakar, Vasa Vemuri, Mariusz Z Ratajczak.

  Cachexia is a multifactorial syndrome characterized by severe muscle wasting and is a debilitating condition frequently associated with cancer. Previous studies from our group revealed that withaferin A (WFA), a steroidal lactone, mitigated muscle cachexia induced by ovarian tumors in NSG mice. However, it remains unclear whether WFA's protective effects are direct or secondary to its antitumor properties. We developed a cachectic model through continuous angiotensin II (Ang II) infusion in C57BL/6 mice to address this issue. Ang II infusion resulted in profound muscle atrophy, evidenced by significant reductions in grip strength and in the TA, GA, and GF muscle mass. Molecular analyses indicated elevated expression of inflammatory cytokines (TNFα, IL-6, MIP-2, IL-18, IL-1β), NLRP3 inflammasome, and genes associated with the UPS (MuRF1, MAFBx) and autophagy pathways (Bacl1, LC3B), along with suppression of anti-inflammatory heme oxygenase-1 (HO-1) and myogenic regulators (Pax7, Myod1). Strikingly, WFA treatment reversed these pathological changes, restoring muscle mass, strength, and molecular markers to near-normal levels. These findings demonstrate that WFA exerts direct anti-cachectic effects by targeting key inflammatory and atrophic pathways in skeletal muscle, highlighting its potential as a novel therapeutic agent for cachexia management.

Keywords:  Ang II; cytokines; muscle cachexia; muscle function; withaferin A

DOI:  https://doi.org/10.3390/cells14040244
Autophagy Rep. 2024 ;pii: 2434379. [Epub ahead of print]3(1):

Alterations of PINK1-PRKN signaling in mice during normal aging.

Zahra Baninameh, Jens O Watzlawik, Xu Hou, Tyrique Richardson, Nicholas W Kurchaba, Tingxiang Yan, Damian N Di Florio, DeLisa Fairweather, Lu Kang, Justin H Nguyen, Takahisa Kanekiyo, Dennis W Dickson, Sachiko Noda, Shigeto Sato, Nobutaka Hattori, Matthew S Goldberg, Ian G Ganley, Kelly L Stauch, Fabienne C Fiesel, Wolfdieter Springer.

  The ubiquitin kinase-ligase pair PINK1-PRKN identifies and selectively marks damaged mitochondria for elimination via the autophagy-lysosome system (mitophagy). While this cytoprotective pathway has been extensively studied in vitro upon acute and complete depolarization of mitochondria, the significance of PINK1-PRKN mitophagy in vivo is less well established. Here we used a novel approach to study PINK1-PRKN signaling in different energetically demanding tissues of mice during normal aging. We demonstrate a generally increased expression of both genes and enhanced enzymatic activity with aging across tissue types. Collectively our data suggest a distinct regulation of PINK1-PRKN signaling under basal conditions with the most pronounced activation and flux of the pathway in mouse heart compared to brain or skeletal muscle. Our biochemical analyses complement existing mitophagy reporter readouts and provide an important baseline assessment in vivo, setting the stage for further investigations of the PINK1-PRKN pathway during stress and in relevant disease conditions.

Keywords:  PINK1; PRKN; aging; brain; heart; mice; mitochondria; mitophagy; phosphorylated ubiquitin; skeletal muscle

DOI:  https://doi.org/10.1080/27694127.2024.2434379
Skelet Muscle. 2025 Feb 24. 15(1): 4

ActRII or BMPR ligands inhibit skeletal myoblast differentiation, and BMPs promote heterotopic ossification in skeletal muscles in mice.

Marc A Egerman, Yuhong Zhang, Romain Donne, Jianing Xu, Abhilash Gadi, Corissa McEwen, Hunter Salmon, Kun Xiong, Yu Bai, Mary Germino, Kevin Barringer, Yasalp Jimenez, Maria Del Pilar Molina-Portela, Tea Shavlakadze, David J Glass.

   BACKGROUND: Prior studies suggested that canonical Activin Receptor II (ActRII) and BMP receptor (BMPR) ligands can have opposing, distinct effects on skeletal muscle depending in part on differential downstream SMAD activation. It was therefore of interest to test ActRII ligands versus BMP ligands in settings of muscle differentiation and in vivo.
METHODS AND RESULTS: In human skeletal muscle cells, both ActRII ligands and BMP ligands inhibited myogenic differentiation: ActRII ligands in a SMAD2/3-dependent manner, and BMP ligands via SMAD1/5. Surprisingly, a neutralizing ActRIIA/B antibody mitigated the negative effects of both classes of ligands, indicating that some BMPs act at least partially through the ActRII receptors in skeletal muscle. Gene expression analysis showed that both ActRII and BMP ligands repress muscle differentiation genes in human myoblasts and myotubes. In mice, hepatic BMP9 over-expression induced liver toxicity, caused multi-organ wasting, and promoted a pro-atrophy gene signature despite elevated SMAD1/5 signaling in skeletal muscle. Local overexpression of BMP7 or BMP9, achieved by intramuscular AAV delivery, induced heterotopic ossification. Elevated SMAD1/5 signaling with increased expression of BMP target genes was also observed in sarcopenic muscles of old rats.
CONCLUSIONS: The canonical ActRII ligand-SMAD2/3 and BMP ligand-SMAD1/5 axes can both block human myoblast differentiation. Our observations further demonstrate the osteoinductive function of BMP ligands while pointing to a potential relevancy of blocking the BMP-SMAD1/5 axis in the setting of therapeutic anti-ActRIIA/B inhibition.

Keywords:  ActRIIA/B; Activin A; BMP; BMPR2; GDF11; GDF8; Heterotopic ossification; Muscle differentiation; Myostatin; Skeletal muscle

DOI:  https://doi.org/10.1186/s13395-025-00373-7
Cell Metab. 2025 Feb 20. pii: S1550-4131(25)00017-8. [Epub ahead of print]

MARIGOLD and MitoCIAO, two searchable compendia to visualize and functionalize protein complexes during mitochondrial remodeling.

Giovanni Rigoni, Enrique Calvo, Christina Glytsou, Marta Carro-Alvarellos, Masafumi Noguchi, Martina Semenzato, Charlotte Quirin, Federico Caicci, Natascia Meneghetti, Mattia Sturlese, Takaya Ishihara, Stefano Moro, Chiara Rampazzo, Naotada Ishihara, Fabrizio Bezzo, Leonardo Salviati, Jesùs Vazquez, Gabriele Sales, Chiara Romualdi, Jose Antonio Enriquez, Luca Scorrano, Maria Eugenia Soriano.

  Mitochondrial proteins assemble dynamically in high molecular weight complexes essential for their functions. We generated and validated two searchable compendia of these mitochondrial complexes. Following identification by mass spectrometry of proteins in complexes separated using blue-native gel electrophoresis from unperturbed, cristae-remodeled, and outer membrane-permeabilized mitochondria, we created MARIGOLD, a mitochondrial apoptotic remodeling complexome database of 627 proteins. MARIGOLD elucidates how dynamically proteins distribute in complexes upon mitochondrial membrane remodeling. From MARIGOLD, we developed MitoCIAO, a mitochondrial complexes interactome tool that, by statistical correlation, calculates the likelihood of protein cooccurrence in complexes. MitoCIAO correctly predicted biologically validated interactions among components of the mitochondrial cristae organization system (MICOS) and optic atrophy 1 (OPA1) complexes. We used MitoCIAO to functionalize two ATPase family AAA domain-containing 3A (ATAD3A) complexes: one with OPA1 that regulates mitochondrial ultrastructure and the second containing ribosomal proteins that is essential for mitoribosome stability. These compendia reveal the dynamic nature of mitochondrial complexes and enable their functionalization.

Keywords:  ATAD3A; OPA1; cristae remodeling; interactome; mitochondria; mitochondrial complexes; mitoribosome stability

DOI:  https://doi.org/10.1016/j.cmet.2025.01.017
J Cachexia Sarcopenia Muscle. 2025 Apr;16(2): e13738

Low-Carbohydrate Diet Exacerbates Denervation-Induced Atrophy of Rat Skeletal Muscle Under the Condition of Identical Protein Intake.

Aki Yokogawa, Kohei Kido, Ikuru Miura, Eisuke Oyama, Daisuke Takakura, Keigo Tanaka, Daniel J Wilkinson, Kenneth Smith, Philip J Atherton, Kentaro Kawanaka.

   BACKGROUND: While decreased protein intake is associated with muscle mass loss, it is unclear whether a decrease in carbohydrate intake adversely affects muscle atrophy independently of protein intake. Herein, we examined whether a low-carbohydrate (low-CHO) diet exacerbates denervation-induced muscle atrophy under conditions of identical protein intake.
METHODS: On day one of the experiment, male Wistar rats underwent unilateral denervation. The contralateral leg was used as the control. After denervation, rats were divided into two dietary groups: high-carbohydrate (high-CHO) and low-CHO. Each group was fed a high-CHO (70% carbohydrate) or low-CHO (20% carbohydrate) diet over 7 days. Total protein and energy intakes in both groups were matched by pair feeding. Rats were provided with deuterium oxide (D2O) tracer over the last 3 days of dietary intervention to quantify myofibrillar (muscle) protein synthesis (MPS).
RESULTS: Denervation reduced wet weight of the gastrocnemius muscle compared to the contralateral control (p < 0.05). Reductions in gastrocnemius muscle weight were greater in the low-CHO group (-34%) than the high-CHO group (-28%) (p < 0.05). Although denervation decreased MPS compared to the contralateral control (p < 0.05), no dietary effect on MPS was observed. Denervation resulted in increased mRNA and protein expression of Atrogin-1, a ubiquitin E3 ligase, compared to that in the contralateral control (p < 0.05). Increases in Atrogin-1 gene and protein expression due to denervation were greater in the low-CHO group than in the high-CHO group (p < 0.05).
CONCLUSIONS: We conclude that a low-CHO diet may exacerbate denervation-induced atrophy in fast-twitch-dominant muscles compared to a high-CHO diet, even when the same protein intake is maintained. Although blunted MPS contributed to muscle atrophy due to denervation, exacerbation of muscle atrophy by the low-CHO diet was not accompanied by explanatory changes in MPS. The effect of the low-CHO diet might be related to promotion of muscle-specific ubiquitin E3 ligase gene expression.

Keywords:  AMPK; Atrogin‐1; deuterium oxide; low‐carbohydrate diet; myofibrillar protein synthesis rate

DOI:  https://doi.org/10.1002/jcsm.13738
J Neurol. 2025 Feb 26. 272(3): 233

Advancements in genetic research and RNA therapy strategies for amyotrophic lateral sclerosis (ALS): current progress and future prospects.

Paola Ruffo, Bryan J Traynor, Francesca Luisa Conforti.

  This review explores the intricate landscape of neurodegenerative disease research, focusing on Amyotrophic Lateral Sclerosis (ALS) and the intersection of genetics and RNA biology to investigate the causative pathogenetic basis of this fatal disease. ALS is a severe neurodegenerative disease characterized by the progressive loss of motor neurons, leading to muscle weakness and paralysis. Despite significant research advances, the exact cause of ALS remains largely unknown. Thanks to the application of next-generation sequencing (NGS) approaches, it was possible to highlight the fundamental role of rare variants with large effect sizes and involvement of portions of non-coding RNA, providing valuable information on risk prediction, diagnosis, and treatment of age-related diseases, such as ALS. Genetic research has provided valuable insights into the pathophysiology of ALS, leading to the development of targeted therapies such as antisense oligonucleotides (ASOs). Regulatory agencies in several countries are evaluating the commercialization of Qalsody (Tofersen) for SOD1-associated ALS, highlighting the potential of gene-targeted therapies. Furthermore, the emerging significance of microRNAs (miRNAs) and long RNAs are of great interest. MiRNAs have emerged as promising biomarkers for diagnosing ALS and monitoring disease progression. Understanding the role of lncRNAs in the pathogenesis of ALS opens new avenues for therapeutic intervention. However, challenges remain in delivering RNA-based therapeutics to the central nervous system. Advances in genetic screening and personalized medicine hold promise for improving the management of ALS. Ongoing clinical trials use genomic approaches for patient stratification and drug targeting. Further research into the role of non-coding RNAs in the pathogenesis of ALS and their potential as therapeutic targets is crucial to the development of effective treatments for this devastating disease.

Keywords:  Amyotrophic lateral sclerosis; Gene-targeted therapies; Next-generation sequencing; Non-coding RNA

DOI:  https://doi.org/10.1007/s00415-025-12975-8
J Nutr. 2025 Feb 22. pii: S0022-3166(25)00098-7. [Epub ahead of print]

Oleuropein supplementation increases resting skeletal muscle fractional PDH activity but does not influence whole-body metabolism: A randomized, double-blind, placebo-controlled trial in healthy, older males.

Philippe Jm Pinckaers, Heather L Petrick, Astrid Mh Horstman, Alba Moreno-Asso, Umberto De Marchi, Floris K Hendriks, Lisa Me Kuin, Cas J Fuchs, Dominik Grathwohl, Lex B Verdijk, Antoine H Zorenc, Joan Mg Senden, Eugenia Migliavacca, Sylviane Metairon, Laure Poquet, Delphine Morin-Rivron, Leonidas G Karagounis, Graham P Holloway, Jerome N Feige, Luc Jc van Loon.

   BACKGROUND: The polyphenol oleuropein activates mitochondrial calcium import, which increases pyruvate dehydrogenase (PDH) activity. Preclinically, this increase in PDH activity following oleuropein supplementation resulted in improved mitochondrial bioenergetics and fatigue resistance.
OBJECTIVE: This study aimed to examine the effects of acute and chronic oleuropein supplementation on muscle energy metabolism, whole-body substrate metabolism, strength, and fatigue resistance in older males.
METHODS: In a randomized, double-blind, placebo-controlled trial, 40 healthy older males (60±5y) received either placebo (PLA) or 100mg oleuropein from olive leaf extract (OLE) supplementation daily for 36 days. On day 1 and 36, muscle and blood samples were collected, and indirect calorimetry was performed, before and up to 120min following supplement intake. Leg strength and fatigue were measured before and after 29 days of supplementation. Results were analyzed using ANCOVA or robust ANCOVA.
RESULTS: OLE ingestion on day 1 and 36 increased plasma oleuropein metabolites (P<0.001). On day 1, no differences were observed in muscle PDH activity, mitochondrial respiration, or whole-body substrate metabolism 120min after acute OLE ingestion. RNA sequencing revealed upregulation of oxidative phosphorylation gene pathways (FDR<0.05), while PDH-Ser293-phosphorylation was higher after acute OLE vs PLA ingestion (P=0.015). Following chronic supplementation, fractional PDH activity was ∼25% greater in OLE vs PLA (49±14 vs 38±10%; P=0.016) with no differences in absolute PDH activity and PDH-Ser293-phosphorylation between groups. Mitochondrial respiration and protein content, whole-body substrate metabolism, leg strength and fatigue resistance, were not different between OLE vs PLA. Plasma LDL cholesterol was lower after chronic OLE vs PLA (P=0.043) with no differences in other blood metabolic markers.
CONCLUSIONS: Chronic OLE supplementation resulted in higher skeletal muscle fractional PDH activity in healthy, older males, which may impact resting energy metabolism. Acute or chronic oleuropein supplementation do not modulate skeletal muscle mitochondrial respiration, muscle strength, muscle fatigue, or whole-body substrate metabolism.
CLINICAL TRIAL REGISTRATION: Https://clinicaltrials.gov/study/NCT05217433. Registry: https://clinicaltrials.gov/study/NCT05217433.

Keywords:  Body composition by MRI; Mitochondrial calcium uniporter; Mitochondrial respiration; Muscle strength; Olea europaea L.; Olive leaf extract; Pyruvate dehydrogenase; Whole-body substrate metabolism

DOI:  https://doi.org/10.1016/j.tjnut.2025.02.015
J Crit Care Med (Targu Mures). 2025 Jan;11(1): 33-43

The effect of pre-existing sarcopenia on outcomes of critically ill patients treated for COVID-19.

Thomas Bradier, Sébastien Grigioni, Céline Savoye-Collet, Gaétan Béduneau, Dorothée Carpentier, Christophe Girault, Maximillien Grall, Grégoire Jolly, Najate Achamrah, Fabienne Tamion, Zoé Demailly.

   Background: Sarcopenia, defined by a loss of skeletal muscle mass and function, has been identified as a prevalent condition associated with poor clinical outcome among critically ill patients. This study aims to evaluate the impact of pre-existing sarcopenia on outcomes in critically ill patients with acute respiratory failure (ARF) due to COVID-19.
Material and Methods: A retrospective study was carried out on COVID-19 patients admitted to intensive care. Pre-existing sarcopenia was assessed using early CT scans. Clinical outcomes, including duration of high-flow oxygenation (HFO), mechanical ventilation (MV), length of hospital stay (LOS) and ICU mortality, were evaluated according to sarcopenia status.
Results: Among the studied population, we found a high prevalence (75 patients, 50%) of pre-existing sarcopenia, predominantly in older male patients. Pre-existing sarcopenia significantly impacted HFO duration (6.8 (+/-4.4) vs. 5 (+/-2.9) days; p=0.005) but did not significantly affect MV requirement (21 (28%) vs. 23 (37.3%); p=185), MV duration (7 vs. 10 days; p=0.233), ICU mortality (12 (16%) vs. 10 (13.3 %); p=0.644) or hospital LOS (27 vs. 25 days; p=0.509). No differences in outcomes were observed between sarcopenic and non-sarcopenic obese patients.
Conclusions: Pre-existing sarcopenia in critically ill COVID-19 patients is associated with longer HFO duration but not with other adverse outcomes. Further research is needed to elucidate the mechanisms and broader impact of sarcopenia on septic critically ill patient outcomes.

Keywords:  COVID-19; Intensive Care Unit; Skeletal Muscle Index; death; sarcopenia; sarcopenic obesity

DOI:  https://doi.org/10.2478/jccm-2024-0045