Sarcopenia, age, atrophy, and myopathy: Mitochondrial oxidative enzyme activities

Pestronk, Alan; Keeling, Richard M.; Choksi, Rati

doi:10.1002/mus.25442

Cited by 10 publications

(3 citation statements)

References 33 publications

(55 reference statements)

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“…According to the previous evidence, the knockdown of NDUFC1 can inhibit complex I function and enhance ROS generation (Han et al, 2022), which may promote the accumulation of mtDNA mutations. The mtDNA damage to sarcopenia and corresponding impaired function may be implicated in the significantly reduced complex I activity in aging skeletal muscles (Marzetti et al, 2009;Pestronk et al, 2017). The present study inferred the significance of mitochondrial dysfunction in the progression of sarcopenia, and the four cuproptosis-related genes, PDHA1, DLAT, PDHB, and NDUFC1, may serve as the potential targets for further therapeutic intervention.…”

Section: Discussionmentioning

confidence: 56%

Identification of the cuproptosis-related hub genes and therapeutic agents for sarcopenia

et al. 2023

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Background: Along with acceleration of population aging, the increasing prevalence of sarcopenia has posed a heavy burden on families as well as society. In this context, it is of great significance to diagnose and intervene sarcopenia as early as possible. Recent evidence has indicated the role of cuproptosis in the development of sarcopenia. In this study, we aimed to seek the key cuproptosis-related genes that can be used for identification and intervention of sarcopenia.Methods: The GSE111016 dataset was retrieved from GEO. The 31 cuproptosis-related genes (CRGs) were obtained from previous published studies. The differentially expressed genes (DEGs) and Weighed gene co-expression network analysis (WGCNA) were subsequently analyzed. The core hub genes were acquired by the intersection of DEGs, WGCNA and CRGs. Through logistic regression analysis, we established a diagnostic model of sarcopenia based on the selected biomarkers and was validated in muscle samples from GSE111006 and GSE167186. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were performed on these genes. Furthermore, the gene set enrichment analysis (GSEA), and immune cell infiltration were also conducted on the identified core genes. Finally, we screened the potential drugs targeting the potential biomarkers of sarcopenia.Results: A total of 902 DEGs and WGCNA containing 1,281 significant genes were preliminarily selected. Intersection of DEGs, WGCNA and CRGs yielded four core genes (PDHA1, DLAT, PDHB, and NDUFC1) as potential biomarkers for the prediction of sarcopenia. The predictive model was established and validated with high AUC values. KEGG pathway and Gene Ontology biological analysis indicated these core genes may play a crucial role in energy metabolism in mitochondria, oxidation process, and aging-related degenerative diseases. In addition, the immune cells may be involved in the development of sarcopenia through mitochondrial metabolism. Finally, metformin was identified as a promising strategy of sarcopenia treatment via targeting NDUFC1.Conclusion: The four cuproptosis-related genes PDHA1, DLAT, PDHB and NDUFC1 may be the diagnostic biomarkers for sarcopenia, and metformin holds great potential to be developed as a therapy for sarcopenia. These outcomes provide new insights for better understanding of sarcopenia and innovative therapeutic approaches.

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Section: Discussionmentioning

confidence: 56%

Identification of the cuproptosis-related hub genes and therapeutic agents for sarcopenia

et al. 2023

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“…The critical role of mitochondria in these organs becomes clinically visible in the case of mitochondrial diseases that frequently affect organs with high energy demand, showing clinical features of encephalopathy, dementia, myopathy, exercise intolerance, cardiomyopathy, optic atrophy, liver failure [ 20 ], and renal pathologies [ 21 ]. In addition, the link between mitochondrial dysfunction and age-related diseases is well-established for Alzheimer’s disease [ 22 ], myocardial infarction, and sarcopenia [ 23 ]. Notably, the role of mitochondria seems to also be crucial in malignant tumor progression [ 24 ], thus, studies that unveil mitochondrial targets, which may serve as potential candidates for new and promising therapeutic strategies against cancer [ 25 ], are needed.…”

Section: Introductionmentioning

confidence: 99%

Targeting Mitochondria to Counteract Age-Related Cellular Dysfunction

Madreiter‐Sokolowski

Sokołowski

Waldeck-Weiermair

et al. 2018

Genes

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Senescence is related to the loss of cellular homeostasis and functions, which leads to a progressive decline in physiological ability and to aging-associated diseases. Since mitochondria are essential to energy supply, cell differentiation, cell cycle control, intracellular signaling and Ca2+ sequestration, fine-tuning mitochondrial activity appropriately, is a tightrope walk during aging. For instance, the mitochondrial oxidative phosphorylation (OXPHOS) ensures a supply of adenosine triphosphate (ATP), but is also the main source of potentially harmful levels of reactive oxygen species (ROS). Moreover, mitochondrial function is strongly linked to mitochondrial Ca2+ homeostasis and mitochondrial shape, which undergo various alterations during aging. Since mitochondria play such a critical role in an organism’s process of aging, they also offer promising targets for manipulation of senescent cellular functions. Accordingly, interventions delaying the onset of age-associated disorders involve the manipulation of mitochondrial function, including caloric restriction (CR) or exercise, as well as drugs, such as metformin, aspirin, and polyphenols. In this review, we discuss mitochondria’s role in and impact on cellular aging and their potential to serve as a target for therapeutic interventions against age-related cellular dysfunction.

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“…La AMPK y las sirtuinas dependientes de NAD + , señalizan una función metabólica importante: la expresión de PGC-1α se ejerce a través de la fosforilación mediada por AMPK y la desacetilación de FOXO3 mediada por SIRT1 requerida para el control de la transcripción completa de PGC-1α (Kjobsted et al, 2017;Pestronk et al, 2017), por lo tanto, el uso de MTF podría activar esta vía, podría mejorar la función mitocondrial.…”

Section: Antecedentesunclassified

Efecto del tratamiento con metformina y ejercicio moderado, sobre la función mitocondrial del músculo esquelético

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Sarcopenia, age, atrophy, and myopathy: Mitochondrial oxidative enzyme activities

Abstract: Mitochondrial oxidative enzyme activities, especially Complex I, but also Complexes II and II+III, are reduced in muscles with the pathologic equivalent of sarcopenia. Individually, atrophy and age have different patterns of oxidative enzyme changes. Muscle Nerve 56: 122-128, 2017.

Cited by 10 publications

References 33 publications

Identification of the cuproptosis-related hub genes and therapeutic agents for sarcopenia

Identification of the cuproptosis-related hub genes and therapeutic agents for sarcopenia

Targeting Mitochondria to Counteract Age-Related Cellular Dysfunction

Efecto del tratamiento con metformina y ejercicio moderado, sobre la función mitocondrial del músculo esquelético

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