Neuron‐specific deletion of CuZnSOD leads to an advanced sarcopenic phenotype in older mice

Bhaskaran, Shylesh; Pollock, Natalie; Macpherson, Peter; Ahn, Bumsoo; Piekarz, Katarzyna M.; Staunton, Caroline; Brown, Jacob L.; Qaisar, Rizwan; Vasilaki, Aphrodite; Richardson, Arlan; McArdle, Anne; Jackson, Malcolm J.; Brooks, Susan V.; Remmen, Holly Van

doi:10.1111/acel.13225

Cited by 37 publications

(35 citation statements)

References 47 publications

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“…These results further support the feasibility of using in vivo redox status assessment in the development of pathological processes such as sarcopenia. Bhaskaran et al 81 . found that neuron‐specific deletion of CuZnSOD was enough to cause the loss of motor neurons in young mice, but damage to neuromuscular junctions, muscle atrophy, and weakness were not obvious until middle age.…”

Section: Classification Of Mouse Models Of Sarcopeniamentioning

confidence: 99%

Mouse models of sarcopenia: classification and evaluation

Xie

Dong-sheng

et al. 2021

J cachexia sarcopenia muscle

113

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Sarcopenia is a progressive and widespread skeletal muscle disease that is related to an increased possibility of adverse consequences such as falls, fractures, physical disabilities and death, and its risk increases with age. With the deepening of the understanding of sarcopenia, the disease has become a major clinical disease of the elderly and a key challenge of healthy ageing. However, the exact molecular mechanism of this disease is still unclear, and the selection of treatment strategies and the evaluation of its effect are not the same. Most importantly, the early symptoms of this disease are not obvious and are easy to ignore. In addition, the clinical manifestations of each patient are not exactly the same, which makes it difficult to effectively study the progression of sarcopenia. Therefore, it is necessary to develop and use animal models to understand the pathophysiology of sarcopenia and develop therapeutic strategies. This paper reviews the mouse models that can be used in the study of sarcopenia, including ageing models, genetically engineered models, hindlimb suspension models, chemical induction models, denervation models, and immobilization models; analyses their advantages and disadvantages and application scope; and finally summarizes the evaluation of sarcopenia in mouse models.

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Section: Classification Of Mouse Models Of Sarcopeniamentioning

confidence: 99%

Mouse models of sarcopenia: classification and evaluation

Xie

Dong-sheng

et al. 2021

J cachexia sarcopenia muscle

113

View full text Add to dashboard Cite

show abstract

“…The disintegration of the neuromuscular junction (NMJ) is a central focal point in the multifactorial etiology of sarcopenia [ 9 ]. We have previously shown that NMJ disintegration can trigger muscle atrophy and weakness in ageing, and conditions associated with increased oxidative stress [ 10 ]. Notably, the muscle shows reduced oxidative capacity, fiber-type grouping, and signs of denervation.…”

Section: Introductionmentioning

confidence: 99%

Prediction of Sarcopenia Using Multiple Biomarkers of Neuromuscular Junction Degeneration in Chronic Obstructive Pulmonary Disease

Karim

Muhammad

Qaisar

2021

JPM

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Patients with chronic obstructive pulmonary disease (COPD) present with an advanced form of age-related muscle loss or sarcopenia. Among multiple pathomechanisms of sarcopenia, neuromuscular junction (NMJ) degradation may be of primary relevance. We evaluated the circulating biomarkers of NMJ degradation, including c-terminal agrin fragment -22 (CAF22), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) as predictors of sarcopenia in COPD during pulmonary rehabilitation (PR). Male, 61–77-year-old healthy controls and patients of COPD (n = 77–84/group) were recruited for measurements of circulating CAF22, BDNF, and GDNF levels. Functional assessment and measurements of plasma biomarkers were performed at diagnosis and following six months of PR. CAF22 levels were elevated while BDNF and GDNF levels were reduced in COPD patients at diagnosis, which were incompletely restored to normal levels following PR. These biomarkers showed varying degrees of associations with indexes of sarcopenia and functional recovery during PR. Logistic regression revealed that the combined use of three biomarkers enhanced the diagnostic accuracy of sarcopenia better than single biomarkers. Altogether, measurements of plasma CAF22, BDNF, and GDNF may be helpful for the accurate diagnosis of sarcopenia and functional capacity in COPD during PR.

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“…It is possible that Sod1KO mice will develop cardiac dysfunction with age. Age-dependent phenotypic manifestation has been reported in this model [ 27 ]. It is interesting to note that deficiency of MnSOD, a superoxide scavenger expressed in mitochondria, has a greater impact on cardiac dysfunction and pathology compared with CnZnSOD.…”

Section: Discussionmentioning

confidence: 88%

Myocardial Hypertrophy and Compensatory Increase in Systolic Function in a Mouse Model of Oxidative Stress

Varshney

Ranjit

Chiao

et al. 2021

IJMS

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Free radicals, or reactive oxygen species, have been implicated as one of the primary causes of myocardial pathologies elicited by chronic diseases and age. The imbalance between pro-oxidants and antioxidants, termed “oxidative stress”, involves several pathological changes in mouse hearts, including hypertrophy and cardiac dysfunction. However, the molecular mechanisms and adaptations of the hearts in mice lacking cytoplasmic superoxide dismutase (Sod1KO) have not been investigated. We used echocardiography to characterize cardiac function and morphology in vivo. Protein expression and enzyme activity of Sod1KO were confirmed by targeted mass spectrometry and activity gel. The heart weights of the Sod1KO mice were significantly increased compared with their wildtype peers. The increase in heart weights was accompanied by concentric hypertrophy, posterior wall thickness of the left ventricles (LV), and reduced LV volume. Activated downstream pathways in Sod1KO hearts included serine–threonine kinase and ribosomal protein synthesis. Notably, the reduction in LV volume was compensated by enhanced systolic function, measured by increased ejection fraction and fractional shortening. A regulatory sarcomeric protein, troponin I, was hyper-phosphorylated in Sod1KO, while the vinculin protein was upregulated. In summary, mice lacking cytoplasmic superoxide dismutase were associated with an increase in heart weights and concentric hypertrophy, exhibiting a pathological adaptation of the hearts to oxidative stress.

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Neuron‐specific deletion of CuZnSOD leads to an advanced sarcopenic phenotype in older mice

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 37 publications

References 47 publications

Mouse models of sarcopenia: classification and evaluation

Mouse models of sarcopenia: classification and evaluation

Prediction of Sarcopenia Using Multiple Biomarkers of Neuromuscular Junction Degeneration in Chronic Obstructive Pulmonary Disease

Myocardial Hypertrophy and Compensatory Increase in Systolic Function in a Mouse Model of Oxidative Stress

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