Molecular changes in transcription and metabolic pathways underlying muscle atrophy in the CuZnSOD null mouse model of sarcopenia

Sataranatarajan, Kavithalakshmi; Pharaoh, Gavin; Brown, Jacob L.; Ranjit, Rojina; Piekarz, Katarzyna M.; Street, Kaitlyn; Wren, Jonathan D.; Georgescu, Constantin; Kinter, Caroline S.; Kinter, Michael; Freeman, Willard M.; Richardson, Arlan; Remmen, Holly Van

doi:10.1007/s11357-020-00189-x

Cited by 22 publications

(22 citation statements)

References 94 publications

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“…The IL‐10(−/−) mouse model can be used to study the pathogenesis of sarcopenia in the presence of inflammation. Another commonly used gene knockout mouse model is the copper zinc superoxide dismutase [CuZnSOD (SOD1)] knockout Sod1(−/−) mouse, which shows many phenotypes of sarcopenia at the age of 5 months 77,78 . Sod1(−/−) mice show high levels of oxidative damage and the characteristics of normal ageing muscles in an accelerated manner and show weakness and destruction of neuromuscular junctions 79 .…”

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

108

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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

108

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“…Indeed, Sod1 −/− has been suggested as a potential tool for studying the pathogenesis of sarcopenia and testing sarcopenia interventions. [55,161]. Furthermore, transgenic mice models can offer novel candidates for musculoskeletal modulators.…”

Section: Genetically Engineered Animal Modelsmentioning

confidence: 99%

“…The premature-aging mice model showed sarcopenia phenotypes and presented a defect in mitochondrial DNA, mitochondrial biogenesis, and mitochondrial dynamics (fission and fusion) [ 53 , 54 ]. In addition, aged mice lacking superoxide anion scavenger ( Sod 1 −/− ) showed mitochondrial hydroperoxide generation and dysregulation of excitation-contraction coupling which contributes to muscle atrophy [ 55 , 56 ]. Indeed, several studies provided evidence that failure in mitochondrial dynamics leads to a negative consequence for the maintenance of muscle mass and function [ 54 , 57 , 58 ].…”

Section: Fundamental Aging Mechanisms That Contribute To Sarcopenimentioning

confidence: 99%

Experimental Models of Sarcopenia: Bridging Molecular Mechanism and Therapeutic Strategy

Mankhong

Kim

Moon

et al. 2020

Cells

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Sarcopenia has been defined as a progressive decline of skeletal muscle mass, strength, and functions in elderly people. It is accompanied by physical frailty, functional disability, falls, hospitalization, and mortality, and is becoming a major geriatric disorder owing to the increasing life expectancy and growing older population worldwide. Experimental models are critical to understand the pathophysiology of sarcopenia and develop therapeutic strategies. Although its etiologies remain to be further elucidated, several mechanisms of sarcopenia have been identified, including cellular senescence, proteostasis imbalance, oxidative stress, and “inflammaging.” In this article, we address three main aspects. First, we describe the fundamental aging mechanisms. Next, we discuss both in vitro and in vivo experimental models based on molecular mechanisms that have the potential to elucidate the biochemical processes integral to sarcopenia. The use of appropriate models to reflect sarcopenia and/or its underlying pathways will enable researchers to understand sarcopenia and develop novel therapeutic strategies for sarcopenia. Lastly, we discuss the possible molecular targets and the current status of drug candidates for sarcopenia treatment. In conclusion, the development of experimental models for sarcopenia is essential to discover molecular targets that are valuable as biochemical biomarkers and/or therapeutic targets for sarcopenia.

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“…Mitochondrial production of H 2 O 2 increases with age in mice [45,46], rats [47,48], and humans [49]. Increases in H 2 O 2 concentration induce atrophy in cell culture models [50], and time-course analysis shows that this increase takes place prior to skeletal muscle atrophy [51]. Exogenous H 2 O 2 also decreases mitochondrial membrane potential that precedes mitochondrial fragmentation, despite no changes in transcripts related to mitochondrial fusion or fission protein expression [52].…”

Section: Mitochondrial Oxidant Productionmentioning

confidence: 99%

Redox Signaling and Sarcopenia: Searching for the Primary Suspect

Foreman

Hesse

2021

IJMS

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Sarcopenia, the age-related decline in muscle mass and function, derives from multiple etiological mechanisms. Accumulative research suggests that reactive oxygen species (ROS) generation plays a critical role in the development of this pathophysiological disorder. In this communication, we review the various signaling pathways that control muscle metabolic and functional integrity such as protein turnover, cell death and regeneration, inflammation, organismic damage, and metabolic functions. Although no single pathway can be identified as the most crucial factor that causes sarcopenia, age-associated dysregulation of redox signaling appears to underlie many deteriorations at physiological, subcellular, and molecular levels. Furthermore, discord of mitochondrial homeostasis with aging affects most observed problems and requires our attention. The search for the primary suspect of the fundamental mechanism for sarcopenia will likely take more intense research for the secret of this health hazard to the elderly to be unlocked.

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Molecular changes in transcription and metabolic pathways underlying muscle atrophy in the CuZnSOD null mouse model of sarcopenia

Cited by 22 publications

References 94 publications

Mouse models of sarcopenia: classification and evaluation

Mouse models of sarcopenia: classification and evaluation

Experimental Models of Sarcopenia: Bridging Molecular Mechanism and Therapeutic Strategy

Redox Signaling and Sarcopenia: Searching for the Primary Suspect

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