Mitochondrial dysfunction: roles in skeletal muscle atrophy

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 26, 2023

Abstract Mitochondria play important roles in maintaining cellular homeostasis and skeletal muscle health, damage to mitochondria can lead a series of pathophysiological changes. Mitochondrial dysfunction atrophy, its molecular mechanism leading atrophy is complex. Understanding the pathogenesis mitochondrial useful for prevention treatment finding drugs methods target modulate function are urgent tasks atrophy. In this review, we first discussed normal muscle. Importantly, described effect on mechanisms involved. Furthermore, regulatory different signaling pathways (AMPK-SIRT1-PGC-1α, IGF-1-PI3K-Akt-mTOR, FoxOs, JAK-STAT3, TGF-β-Smad2/3 NF-κB pathways, etc.) factors were investigated dysfunction. Next, analyzed manifestations caused by diseases. Finally, summarized preventive therapeutic effects targeted regulation including drug therapy, exercise diet, gene stem cell therapy physical therapy. This review great significance holistic understanding role muscle, which helpful researchers further has an inspiring development strategies targeting future.

Language: Английский

---

An update on chronic complications of diabetes mellitus: from molecular mechanisms to therapeutic strategies with a focus on metabolic memory

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: May 26, 2024

Abstract Diabetes mellitus, a chronic metabolic disease, often leads to numerous complications, significantly contributing global morbidity and mortality rates. High glucose levels trigger epigenetic modifications linked pathophysiological processes like inflammation, immunity, oxidative stress, mitochondrial dysfunction, senescence various kinds of cell death. Despite glycemic control, transient hyperglycemia can persistently harm organs, tissues, cells, latent effect termed "metabolic memory" that contributes diabetic complications. Understanding memory's mechanisms could offer new approach mitigating these However, key molecules networks underlying memory remain incompletely understood. This review traces the history research, highlights its features, discusses recent involved in mechanisms, summarizes confirmed potential therapeutic compounds. Additionally, we outline vitro vivo models memory. We hope this work will inform future research on regulatory facilitate development effective compounds prevent

Language: Английский

---

Mitochondrial quality control: a pathophysiological mechanism and potential therapeutic target for chronic obstructive pulmonary disease

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 3, 2025

Chronic obstructive pulmonary disease (COPD) is a prevalent chronic respiratory worldwide. Mitochondrial quality control mechanisms encompass processes such as mitochondrial biogenesis, fusion, fission, and autophagy, which collectively maintain the quantity, morphology, function of mitochondria, ensuring cellular energy supply progression normal physiological activities. However, in COPD, due to persistent stimulation harmful factors smoking air pollution, often become deregulated, leading dysfunction. dysfunction plays pivotal role pathogenesis contributing toinflammatory response, oxidative stress, senescence. therapeutic strategies targeting mitochondria remain underexplored. This review highlights recent advances focusing on their dysregulation progression. We emphasize significance pathophysiological COPD explore potential regulate improve through interventions, aiming treat effectively. Additionally, we analyze limitations challenges existing strategies, provide new insights methods for treatment.

Language: Английский

---

GLP-1RA Liraglutide and Semaglutide Improves Obesity-Induced Muscle Atrophy via SIRT1 Pathway

Diabetes Metabolic Syndrome and Obesity, Journal Year: 2023, Volume and Issue: Volume 16, P. 2433 - 2446

Published: Aug. 1, 2023

Obesity is related to the loss of skeletal muscle mass and function (sarcopenia). The co-existence obesity sarcopenia called sarcopenic (SO). Glucagon like peptide-1 receptor agonists (GLP-1RA) are widely used in treatment diabetes obesity. However, protective effects GLP-1RA on SO not clear. This study investigated liraglutide semaglutide obesity-induced atrophy explored underlying mechanisms.Thirty-six male C57BL/6J mice were randomly divided into two groups fed a regular diet high-fat for 18 weeks, respectively. After establishing an model, further six groups: control group, (LIRA) (SEMA) (HFD) HFD + LIRA SEMA subcutaneous injection 4 weeks. body weight, mass, strength, glycolipid metabolism, markers, myogenic differentiation GLUT4 SIRT1 analyzed. C2C12 myotube cells treated with palmitic acid (PA) four PA group. changes glucose uptake, diameter, lipid droplet infiltration, markers atrophy, analyzed, indicators observed after addition inhibitor EX527.Liraglutide reduced HFD-induced weight gain, excessive accumulation improved atrophy. Liraglutide eliminated increase myotubes. restored impaired tolerance insulin resistance. these beneficial attenuated by inhibiting expression.Liraglutide protects against via pathway.

Language: Английский

---

Multiomics Analysis Reveals Therapeutic Targets for Chronic Kidney Disease With Sarcopenia

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 1, 2025

ABSTRACT Background The presence of sarcopenia in patients with chronic kidney disease (CKD) is associated poor prognosis. mechanism underlying CKD‐induced muscle wasting has not yet been fully explored. This study investigates the influence renal secretions on muscles using multiomics sequencing. Methods transcriptome analysis by RNA‐seq and protein profiling tandem mass tag (TMT), serum TMT were performed CKD established 0.2% adenine control mice. Spp1 recombinant was used to its effect myotube atrophy vitro. In animal experiments CKD, pharmacological inhibition explore role skeletal wasting. Transcriptome identify differentially expressed genes (DEGs) gastrocnemius following inhibition. Results TMT, 503 377 proteins/genes respectively co‐upregulated co‐downregulated. normal (NC) mice, 22 upregulated 7 downregulated proteins (DEPs) showed same expression patterns as those analysis. Based bioinformatics reported studies, we selected for further validation. added C2C12 myotubes vitro, results indicated that significantly increased levels marker (Murf‐1) promoted smaller (all p < 0.05). Compared NC mRNA kidneys concentration also markedly experiments, weights tibialis anterior ( 0.05) improved phenotype. DEGs enriched digestion absorption, glucagon signalling pathway, apelin pathway ECM‐receptor interaction pathway. Conclusions Our first establish a regulatory network kidney‐muscle crosstalk potential CKD‐related sarcopenia. Employing analysis, cellular assessment have identified could potentialy serve promising therapeutic target

Language: Английский

---

Combating chronic kidney disease-associated cachexia: A literature review of recent therapeutic approaches

BMC Nephrology, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 11, 2025

In 2008, the Society on Sarcopenia, Cachexia, and Wasting Disorders introduced a generic definition for all types of cachexia: "a complex metabolic syndrome associated with underlying illness characterized by loss muscle, or without fat loss". It is well-known that presence inflammatory burden in end-stage renal disease (ESRD) patients may lead to evolution cachexia. Since etiology cachexia chronic kidney (CKD) multifactorial, thus successful treatment must involve several concomitant measures (nutritional interventions, appetite stimulants, anti-inflammatory pharmacologic agents) provide integrated effective therapeutic modalities combat causative factors alleviate outcomes patients. Given high mortality rate cachexia, developing new are prerequisite ameliorating CKD worldwide. The present review aims discuss some strategies an update advances nutritional approaches counteract

Language: Английский

---

Thioredoxin-1 Promotes Mitochondrial Biogenesis Through Regulating AMPK/Sirt1/PGC1α Pathway in Alzheimer's Disease

ASN NEURO, Journal Year: 2023, Volume and Issue: 15, P. 175909142311592 - 175909142311592

Published: Jan. 1, 2023

Alzheimer's disease (AD) is the most common neurodegenerative disease. Increasing studies suggest that mitochondrial dysfunction closely related to pathogenesis of AD. Thioredoxin-1 (Trx-1), one major redox proteins in mammalian cells, plays neuroprotection However, whether Trx-1 could regulate biogenesis AD largely unknown. In present study, we found Aβ 25−35 treatment not only markedly induced excessive production reactive oxygen species and apoptosis, but also significantly decreased number mitochondria with biological activity adenosine triphosphate content mitochondria, suggesting was impaired cells. These changes were reversed by Lentivirus-mediated stable overexpression or exogenous administration recombinant human Trx-1. What's more, adeno-associated virus-mediated specific hippocampus β-amyloid precursor protein/presenilin 1 (APP/PS1) mice ameliorated learning memory attenuated hippocampal deposition. Importantly, APP/PS1 restored decrease biogenesis-associated proteins, including monophosphate -activated protein kinase (AMPK), silent information regulator factor 2-related enzyme (Sirt1) peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α). addition, rat adrenal pheochromocytoma (PC12) cells AMPK, Sirt1, PGC1α treatment. Pharmacological inhibition AMPK abolished effect on biogenesis. Taken together, our data provide evidence promoted via restoring AMPK/Sirt1/PGC1α pathway

Language: Английский

---

Propofol Inhibits Oxidative Stress-Induced Neuronal Cell Ferroptosis and Promotes Synaptic Plasticity via the AMPK/ SIRT1/PGC-1α Axis

Indian Journal of Pharmaceutical Education and Research, Journal Year: 2025, Volume and Issue: 59(1), P. 185 - 195

Published: Jan. 6, 2025

Aim/Background Propofol, recognized for its quick and effective action as a hypnotic anesthetic, is frequently utilized in clinical practice. Our research intended to investigate the mechanism by which propofol inhibits neuronal ferroptosis promotes synaptic plasticity via mitochondrial energy regulation. Materials Methods Mouse Hippocampal Neurons (HT22) cells were treated with RAS-Selective Lethal 3 (RSL3) followed Reactive Oxygen species (ROS) detection. Expression levels of regulation analyzed. HT22 Sirtuin 1 (SIRT1) inhibitor before treatment. Level ROS, Fe2+ genes expression measured. Results In RSL3-Low+propofol cohort, exhibiting stark contrast both mock group RSL3-High+propofol group, administration notably attenuated Cyclooxygenase 2 (COX-2) Long-chain-fatty-acid-CoA Ligase 4 (ACSL4), while concurrently enhancing Glutathione Peroxidase (GPX4), Solute Carrier Family 7 Member 11 (SLC7A11), Nuclear Factor-like (NRF2), Ferritin Heavy chain (FTH1), Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase (AMPK), SIRT1 PPARγ Coactivator-1 α (PGC-1α). ROS substantially greater Selisistat+propofol than whereas PGC-1α considerably less comparison groups. Conversely, showed significantly higher AMPK, SIRT1, PGC-1α, Synapsin-1 (SYN1) PSD-95 compared (p <0.05). Conclusion Propofol oxidative stress-induced cell AMPK/ SIRT1/PGC-1α axis.

Language: Английский

---

Network Pharmacology Combined with Experimental Validation to Investigate the Effects and Mechanisms of Aucubin on Aging-Related Muscle Atrophy

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2626 - 2626

Published: March 14, 2025

Aucubin (AU) is one of the main components traditional Chinese medicine Eucommia ulmoides Oliv (EU). This study investigated effects AU on aging-related skeletal muscle atrophy in vitro and vivo. The results network pharmacology revealed potential therapeutic atrophy. In vitro, effectively attenuated D-gal-induced cellular damage, reduced number senescence-associated β-galactosidase (SA-β-Gal)-positive cells, down-regulated expression levels atrophy-related proteins Atrogin-1 MuRF1, improved myotube differentiation, thereby mitigating Notably, was found to attenuate oxidative stress apoptosis cells by reducing ROS production, regulating Cleaved caspase3 BAX/Bcl-2 apoptotic pathways, enhancing Sirt1 PGC-1α signaling pathways. vivo studies demonstrated that treatment extended average lifespan Caenorhabditis elegans (C. elegans), increased locomotor activity, body wall mitochondrial content, alleviated damage C. elegans. These findings suggested can ameliorate show significant preventing treating

Language: Английский

---

Inhibiting Myostatin Expression by the Antisense Oligonucleotides Improves Muscle Wasting in a Chronic Kidney Disease Mouse Model

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3098 - 3098

Published: March 27, 2025

Sarcopenia, a serious consequence of chronic kidney disease (CKD), is driven by elevated myostatin (MSTN), key inhibitor muscle growth. This study explored the potential an MSTN-specific antisense oligonucleotide (ASO) in reversing CKD-induced wasting mouse model. Thirty-two male C57BL/6J mice were randomly assigned to non-CKD group (n = 8, regular diet) and CKD 24, adenine diet). was induced using 0.2% adenine-supplemented diet for 4 weeks. Following this, sub-grouped into (saline, n 8), + Low-Dose ASO (25 mg/kg ASO, High-Dose (50 8). administered via subcutaneous injections 8 Muscle mass, treadmill performance, grip strength, fiber morphology assessed alongside qPCR Western blot analysis MSTN, atrogin-1, MuRF-1 expression. therapy significantly enhanced mass function enlarged fibers while effectively downregulating degradation markers. These improvements occurred without compromising renal function, as confirmed BUN, creatinine, weight, histological analysis. first demonstrate efficacy mitigating sarcopenia, offering promising targeted gene with significant clinical implications improving nutritional status physical performance CKD.

Language: Английский

---