Redox Signaling and Sarcopenia: Searching for the Primary Suspect

Foreman, Nicholas A.; Hesse, Anton S.; Ji, Li Li

doi:10.3390/ijms22169045

Cited by 35 publications

(30 citation statements)

References 196 publications

(300 reference statements)

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“…These results were consistent with the performance of mitochondrial dysfunction in diabetic skeletal muscle. A recent study had described that the glutathione pathway plays a positively substantial role in removing ROS and skeletal muscle mass by modulating redox homeostasis [42][43][44][45] which is consistent with our findings with the down-regulated glutathione pathway in db/db mice.…”

Section: Discussionsupporting

confidence: 93%

The Whole-Transcriptome Landscape of Diabetes-Related Sarcopenia Reveals the Specific Function of Novel lncRNA Gm20743

Loh²,

Yang³

et al. 2022

Preprint

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Background: While the exact mechanism remains unclear, type 2 diabetes mellitus (T2DM) has been shown to increase the risk of sarcopenia that is characterized by decreased muscle mass, strength, and function. This study aimed to identify the pathophysiological role of lncRNAs in diabetic sarcopenia. Methods: Whole-transcriptome RNA sequencing was performed on the gastrocnemius from the overt diabetes-induced sarcopenia model of db/db mice. Informatics and co-expression networks were performed to predict key lncRNAs and their potential regulation circuits in diabetes-induced sarcopenia. To determine the specific function of lncRNA Gm20743, the detection of Mito-Sox, reactive oxygen species, Ethynyl-2′-deoxyuridine, and myosin heavy chain was performed in overexpressed-Gm20743 C2C12 cells. Results: RNA-seq data and informatics revealed the key lncRNA-mRNA interactions and indicated a potential regulatory role of lncRNAs. Meanwhile, we characterized three core candidate lncRNAs Gm20743, Gm35438, and 1700047G03Rik and their potential function. Furthermore, the results suggested lncRNA Gm20743 may be involved in regulating mitochondrial function, oxidative stress, cell proliferation, and myotube differentiation in skeletal muscle cells. Conclusion: These findings significantly improve our understanding of lncRNAs that may mediate muscle mass, strength, and function in diabetes and represent potential therapeutic targets for diabetes-induced sarcopenia.

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Section: Discussionsupporting

confidence: 93%

The Whole-Transcriptome Landscape of Diabetes-Related Sarcopenia Reveals the Specific Function of Novel lncRNA Gm20743

Loh²,

Yang³

et al. 2022

Preprint

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show abstract

“…TNFα, IL-1B, IL-1, and IL-6 also directly inhibit phosphoinositide 3-kinases (PI3Ks)/Protein kinase B (Akt) activity and protein synthesis pathway. In this way, IL-6 reduces skeletal muscle by signaling its receptor ( 14 ). In sarcopenia, there is an increase in the levels of inflammatory factors, including TNF-α, IL-1, and IL-6, and this increase is associated with a decrease in muscle mass.…”

Section: Interleukinsmentioning

confidence: 99%

“…Then activated NF-KB with FOXO1 acts synergistically, increasing the expression of pro-inflammatory factors such as IL-1β ( 114 ). On the other hand, inflammation is associated with FOXO activation and myostatin overexpression, which in turn can cause NF-KB-independent muscle atrophy ( 14 ). One study found that the expression of SMAD and FOXO increased myostatin promoter activity and inhibited myoblast differentiation ( 115 ).…”

Section: Effects Of Exercise and Sarcopenia Obesity On Protein Degrad...mentioning

confidence: 99%

“…But TNFα, IL-1B, IL-1, and IL-6 directly inhibit PI3K/Akt activity and thus eliminate their inhibition of FOXO. IL-6 has also been shown to reduce skeletal muscle by signaling its receptor, which activates FOXO3 ( 14 ) ( Figure 1 ). However, when Akt is inhibited in aging muscles, FOXO translocation occurs, increasing the expression of atrophy-related genes such as Atrogin-1 and MuRF-1.…”

Section: Effects Of Exercise and Sarcopenia Obesity On Protein Degrad...mentioning

confidence: 99%

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Exercise Therapy for People With Sarcopenic Obesity: Myokines and Adipokines as Effective Actors

Pahlavani

2022

Front. Endocrinol.

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Sarcopenic obesity is defined as a multifactorial disease in aging with decreased body muscle, decreased muscle strength, decreased independence, increased fat mass, due to decreased physical activity, changes in adipokines and myokines, and decreased satellite cells. People with sarcopenic obesity cause harmful changes in myokines and adipokines. These changes are due to a decrease interleukin-10 (IL-10), interleukin-15 (IL-15), insulin-like growth factor hormone (IGF-1), irisin, leukemia inhibitory factor (LIF), fibroblast growth factor-21 (FGF-21), adiponectin, and apelin. While factors such as myostatin, leptin, interleukin-6 (IL-6), interleukin-8 (IL-8), and resistin increase. The consequences of these changes are an increase in inflammatory factors, increased degradation of muscle proteins, increased fat mass, and decreased muscle tissue, which exacerbates sarcopenia obesity. In contrast, exercise, especially strength training, reverses this process, which includes increasing muscle protein synthesis, increasing myogenesis, increasing mitochondrial biogenesis, increasing brown fat, reducing white fat, reducing inflammatory factors, and reducing muscle atrophy. Since some people with chronic diseases are not able to do high-intensity strength training, exercises with blood flow restriction (BFR) are newly recommended. Numerous studies have shown that low-intensity BFR training produces the same increase in hypertrophy and muscle strength such as high-intensity strength training. Therefore, it seems that exercise interventions with BFR can be an effective way to prevent the exacerbation of sarcopenia obesity. However, due to limited studies on adipokines and exercises with BFR in people with sarcopenic obesity, more research is needed.

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“…On the other hand, RNS can be neutralized by hemoglobin, uric acid, β-carotene, vitamins E and C, as well as by SOD, glutathione peroxidase and thioredoxin [ 127 ]. These antioxidant systems allow a fine-tune balance of ROS levels, and disruption of this equilibrium can cause OS, a condition implicated in the progression of different skeletal muscle affections, including sarcopenia and different types of myopathies [ 6 , 128 ]. The redox imbalance may be due to an increased production of O 2 •− or a reduced neutralization of ROS and RNS.…”

Section: Oxidative Stress In Muscular Dystrophiesmentioning

confidence: 99%

Oxidative Stress, Inflammation and Connexin Hemichannels in Muscular Dystrophies

et al. 2022

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Muscular dystrophies (MDs) are a heterogeneous group of congenital neuromuscular disorders whose clinical signs include myalgia, skeletal muscle weakness, hypotonia, and atrophy that leads to progressive muscle disability and loss of ambulation. MDs can also affect cardiac and respiratory muscles, impairing life-expectancy. MDs in clude Duchenne muscular dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy and limb-girdle muscular dystrophy. These and other MDs are caused by mutations in genes that encode proteins responsible for the structure and function of skeletal muscles, such as components of the dystrophin-glycoprotein-complex that connect the sarcomeric-actin with the extracellular matrix, allowing contractile force transmission and providing stability during muscle contraction. Consequently, in dystrophic conditions in which such proteins are affected, muscle integrity is disrupted, leading to local inflammatory responses, oxidative stress, Ca2+-dyshomeostasis and muscle degeneration. In this scenario, dysregulation of connexin hemichannels seem to be an early disruptor of the homeostasis that further plays a relevant role in these processes. The interaction between all these elements constitutes a positive feedback loop that contributes to the worsening of the diseases. Thus, we discuss here the interplay between inflammation, oxidative stress and connexin hemichannels in the progression of MDs and their potential as therapeutic targets.

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Redox Signaling and Sarcopenia: Searching for the Primary Suspect

Cited by 35 publications

References 196 publications

The Whole-Transcriptome Landscape of Diabetes-Related Sarcopenia Reveals the Specific Function of Novel lncRNA Gm20743

The Whole-Transcriptome Landscape of Diabetes-Related Sarcopenia Reveals the Specific Function of Novel lncRNA Gm20743

Exercise Therapy for People With Sarcopenic Obesity: Myokines and Adipokines as Effective Actors

Oxidative Stress, Inflammation and Connexin Hemichannels in Muscular Dystrophies

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