Declined expressions of vast mitochondria-related genes represented by CYCS and transcription factor ESRRA in skeletal muscle aging

Kan, Jingbao; Hu, Yifang; Ge, Yaoqi; Zhang, Wensong; Lü, Shan; Zhao, Chuanzhi; Zhang, Rihua; Liu, Yun

doi:10.1080/21655979.2021.1948951

Cited by 12 publications

(13 citation statements)

References 56 publications

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“…Members of FAM protein family (FAM151a, FAM13a, FAM131a, FAM20c), LGI1 and MYLK3 were also significant DEGs in our study (|log 2 FC|>1). Another transcriptome study analyzed the gene expression data files of human and rats from the Gene Expression Omnibus (GEO) database ( 27 ). Results showed that the expression of mitochondria genes involved in mitochondrial electron transport, complex assembly of the respiratory chain, TCA cycle, oxidative phosphorylation and ATP synthesis were down-regulated in skeletal muscle with aging.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, increasing studies have utilized transcriptome technology to explore the pathogenesis of sarcopenia in recent years. Some muscle mass and function related genes such as AMPK, IGF-1, CASK, MGMT, UCP3, strength related genes Tnnc1, TPM3, and other metabolism related genes have been verified (26)(27)(28)(29)(30). However, we still lack researches on hormone-related sarcopenia on the transcriptome level.…”

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confidence: 99%

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An integrated study of hormone-related sarcopenia for modeling and comparative transcriptome in rats

et al. 2023

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Sarcopenia is a senile disease with high morbidity, serious complications and limited clinical treatments. Menopause increases the risk of sarcopenia in females, while the exact pathogenesis remains unclear. To systematically investigate the development of hormone-related sarcopenia, we established a model of sarcopenia by ovariectomy and recorded successive characteristic changes. Furthermore, we performed the transcriptome RNA sequencing and bioinformatics analysis on this model to explore the underlying mechanism. In our study, we identified an integrated model combining obesity, osteoporosis and sarcopenia. Functional enrichment analyses showed that most of the significantly enriched pathways were down-regulated and closely correlated with endocrine and metabolism, muscle dysfunction, cognitive impairment and multiple important signaling pathways. We finally selected eight candidate genes to verify their expression levels. These findings confirmed the importance of estrogen in the maintenance of skeletal muscle function and homeostasis, and provided potential targets for further study on hormone-related sarcopenia.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

An integrated study of hormone-related sarcopenia for modeling and comparative transcriptome in rats

et al. 2023

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“…Hence, we find that genes overexpressed in skeletal muscle atrophy are also found to be prioritized in other diseases such as cancer, and neurodegenerative diseases. Mitochondria-related gene MRPS21 has been identified here as well, whose declined expression has been found in sarcopenia or age-related skeletal muscle deterioration [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Detection of Target Genes for Drug Repurposing to Treat Skeletal Muscle Atrophy in Mice Flown in Spaceflight

Manian

Orozco-Sandoval

Díaz-Martínez

et al. 2022

Genes

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Skeletal muscle atrophy is a common condition in aging, diabetes, and in long duration spaceflights due to microgravity. This article investigates multi-modal gene disease and disease drug networks via link prediction algorithms to select drugs for repurposing to treat skeletal muscle atrophy. Key target genes that cause muscle atrophy in the left and right extensor digitorum longus muscle tissue, gastrocnemius, quadriceps, and the left and right soleus muscles are detected using graph theoretic network analysis, by mining the transcriptomic datasets collected from mice flown in spaceflight made available by GeneLab. We identified the top muscle atrophy gene regulators by the Pearson correlation and Bayesian Markov blanket method. The gene disease knowledge graph was constructed using the scalable precision medicine knowledge engine. We computed node embeddings, random walk measures from the networks. Graph convolutional networks, graph neural networks, random forest, and gradient boosting methods were trained using the embeddings, network features for predicting links and ranking top gene-disease associations for skeletal muscle atrophy. Drugs were selected and a disease drug knowledge graph was constructed. Link prediction methods were applied to the disease drug networks to identify top ranked drugs for therapeutic treatment of skeletal muscle atrophy. The graph convolution network performs best in link prediction based on receiver operating characteristic curves and prediction accuracies. The key genes involved in skeletal muscle atrophy are associated with metabolic and neurodegenerative diseases. The drugs selected for repurposing using the graph convolution network method were nutrients, corticosteroids, anti-inflammatory medications, and others related to insulin.

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“…Hypothyroidism and thyroid receptor deficiency, which causes skeletal muscle weakness leads to a simultaneous suppression of mitochondrial metabolic genes, transcription factor A, mitochondrial (TFAM), peroxisome proliferator activator receptor co-activator 1 alpha (PGC1) and ERR expression in the muscle [48]. Aging associated sarcopenia and muscle loss has also been shown to corelate with downregulation of mitochondrial genes linked to tricarboxylic acid cycle, electron transport/respiratory chain, oxidative phosphorylation along with ERR [49]. Likewise, skeletal muscle unloading and reloading, which affects muscle function and mass, suppresses or stimulates the expression of ERRs, respectively [50,51].…”

Section: Expression Of Errs In the Skeletal Musclementioning

confidence: 99%

Estrogen-related Receptor Signaling in Skeletal Muscle Fitness

Sopariwala¹,

Nguyen²,

Narkar³

2023

Int J Sports Med

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Skeletal muscle is a highly plastic tissue which can alter its metabolic and contractile features, as well as regenerative potential in response to exercise and other conditions. Multiple signaling factors including metabolites, kinases, receptors and transcriptional factors have been studied in the regulation of skeletal muscle plasticity. Recently, estrogen-related receptors (ERRs) have emerged as a critical transcriptional hub in control of skeletal muscle homeostasis. ERRα and ERRγ - the two highly expressed ERR sub-types in the muscle respond to various extracellular cues such as exercise, hypoxia, fasting and dietary factors, in turn regulating gene expression in the skeletal muscle. On the other hand, conditions such as diabetes and muscular dystrophy suppress expression of ERRs in the skeletal muscle, likely contributing to disease progression. We highlight key functions of ERRs in the skeletal muscle including the regulation of fiber type, mitochondrial metabolism, vascularization and regeneration. We also describe how ERRs are regulated in the skeletal muscle, and their interaction with important muscle regulators (e.g. AMPK and PGCs). Finally, we identify critical gaps in our understanding of ERR signaling in the skeletal muscle, and suggest future areas of investigation to advance ERRs as potential targets for function promoting therapeutics in muscle diseases.

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Declined expressions of vast mitochondria-related genes represented by CYCS and transcription factor ESRRA in skeletal muscle aging

Cited by 12 publications

References 56 publications

An integrated study of hormone-related sarcopenia for modeling and comparative transcriptome in rats

An integrated study of hormone-related sarcopenia for modeling and comparative transcriptome in rats

Detection of Target Genes for Drug Repurposing to Treat Skeletal Muscle Atrophy in Mice Flown in Spaceflight

Estrogen-related Receptor Signaling in Skeletal Muscle Fitness

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