Sarcopenia: Molecular regulatory network for loss of muscle mass and function

Wu, Jiaxiang; Ding, Pingan; Wu, Haotian; Yang, Peigang; Guo, Honghai; Tian, Yuan; Meng, Lingjiao; Zhao, Qun

doi:10.3389/fnut.2023.1037200

Cited by 12 publications

(7 citation statements)

References 103 publications

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“…Also, research has shown a connection between Atrogin-1/MAFbx and cardiac hypertrophy [ 38 ]. MuRF-1 have been identified as essential enzymes in ubiquitin-mediated proteolysis and muscle atrophy, and modulating their expression via physical activity or targeting the upstream cytokines and growth factors that regulate their expression has the potential to prevent or reverse muscle atrophy in patients with sarcopenia [ 39 , 40 ]. The key mechanism is made up by the acceleration of muscle protein degradation in muscle involving an increase in the expression and activity of two muscle-specific, E3 Ub ligases, Atrogin-1 (also known as MAFbx) and MuRF-1 [ 34 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Evidence that tirzepatide protects against diabetes-related cardiac damages

Taktaz,

Scisciola,

Fontanella

et al. 2024

Cardiovasc Diabetol

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Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their impact on heart failure (HF) remains unclear. Therefore, our study examined the cardioprotective effects of tirzepatide (TZT), a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist. Methods A three-steps approach was designed: (i) Meta-analysis investigation with the primary objective of assessing major adverse cardiovascular events (MACE) occurrence from major randomized clinical trials.; (ii) TZT effects on a human cardiac AC16 cell line exposed to normal (5 mM) and high (33 mM) glucose concentrations for 7 days. The gene expression and protein levels of primary markers related to cardiac fibrosis, hypertrophy, and calcium modulation were evaluated. (iii) In silico data from bioinformatic analyses for generating an interaction map that delineates the potential mechanism of action of TZT. Results Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40–0.79, Heterogeneity: r2 = 0.01, I2 = 23.45%, H2 = 1.31). In the human AC16 cardiac cell line treatment with 100 nM TZT contrasted high glucose (HG) levels increase in the expression of markers associated with fibrosis, hypertrophy, and cell death (p < 0.05 for all investigated markers). Bioinformatics analysis confirmed the interaction between the analyzed markers and the associated pathways found in AC16 cells by which TZT affects apoptosis, fibrosis, and contractility, thus reducing the risk of heart failure. Conclusion Our findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Evidence that tirzepatide protects against diabetes-related cardiac damages

Taktaz,

Scisciola,

Fontanella

et al. 2024

Cardiovasc Diabetol

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“…On the other hand, as animals age, there is a gradual decline in their muscle mass, strength, and function, resulting in a condition known as sarcopenia. 6 , 7 Although the factors contributing to sarcopenia have been investigated from various aspects, including alterations in muscle protein synthesis, mitochondrial function, and inflammation, 8 there has been limited exploration of the structural changes in Z-disks and M-lines associated with sarcopenia.…”

Section: Introductionmentioning

confidence: 99%

RSU-1 regulates the integrity of dense bodies in muscle cells of aging Caenorhabditis elegans

Jiang,

Wang,

Zhang

et al. 2024

iScience

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“… 6 Muscle atrophy is primarily caused by an imbalance between protein synthesis and degradation. 7 Ubiquitin-proteasome system (UPS) activation leads to increased protein degradation within muscles and is closely associated with skeletal muscle atrophy. 8 One characteristic of muscle atrophy is a reduction in myofibrillar proteins because of excessive activation of the ubiquitin–proteasome pathway, which often manifests by increased expression of muscle-specific ubiquitin ligases Fbxo32 (Atrogin-1, MAFbx) and Trim63 (MuRF1), 9 which are recognized as pivotal genes in the regulation of muscle atrophy.…”

Section: Introductionmentioning

confidence: 99%

HucMSCs Delay Muscle Atrophy After Peripheral Nerve Injury Through Exosomes by Repressing Muscle-Specific Ubiquitin Ligases

Chen,

Zhu,

Gao

et al. 2024

Stem Cells

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Cell therapy based on mesenchymal stem cells (MSCs) alleviates muscle atrophy caused by diabetes and aging，however, the impact of human umbilical cord mesenchymal stem cells on muscle atrophy following nerve injury and the underlying mechanisms remain unclear. In this study, we evaluated the therapeutic efficacy of human umbilical cord MSCs (hucMSCs) and hucMSC-derived exosomes (hucMSC-EXOs) for muscle atrophy following nerve injury and identified the underlying molecular mechanisms. Sciatic nerve crush injury in rats and the induction of myotubes in L6 cells were used to determine the ameliorating effect of hucMSCs and hucMSC-EXOs on muscle atrophy. Q-PCR and western blot analyses were used to measure the expression of muscle-specific ubiquitin ligases Fbxo32 (Atrogin1, MAFbx) and Trim63 (MuRF-1). Dual-luciferase reporter gene experiments were conducted to validate the direct binding of miRNAs to their target genes. Local injection of hucMSCs and hucMSC-EXOs mitigated atrophy in the rat gastrocnemius muscle following sciatic nerve crush injury. In vitro, hucMSC-EXOs alleviated atrophy in L6 myotubes. Mechanistic analysis indicated the upregulation of miR-23b-3p levels in L6 myotubes following hucMSC-EXOs treatment. MiR-23b-3p significantly inhibited the expression of its target genes, Fbxo32 and Trim63, and suppressed myotube atrophy. Notably, a miR-23b-3p inhibitor reversed the inhibitory effect of miR-23b-3p on myotube atrophy in vitro. These results suggest that hucMSCs and their exosomes alleviate muscle atrophy following nerve injury. MiR-23b-3p in exosomes secreted by hucMSCs contributes to this mechanism by inhibiting the muscle specific ubiquitination ligases Fbxo32 and Trim63.

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Sarcopenia: Molecular regulatory network for loss of muscle mass and function

Cited by 12 publications

References 103 publications

Evidence that tirzepatide protects against diabetes-related cardiac damages

Evidence that tirzepatide protects against diabetes-related cardiac damages

RSU-1 regulates the integrity of dense bodies in muscle cells of aging Caenorhabditis elegans

HucMSCs Delay Muscle Atrophy After Peripheral Nerve Injury Through Exosomes by Repressing Muscle-Specific Ubiquitin Ligases

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