Applications, limitations, and prospects of different muscle atrophy models in sarcopenia and cachexia research

(Press-News.org) With the intensification of global population aging, muscle atrophy, characterized by the loss of muscle mass and function, has become an important health issue affecting the elderly. Researchers have widely used various animal and cellular models to gain a deeper understanding of the pathophysiological mechanisms of muscle atrophy and develop effective treatment strategies (Figure 1). These models simulate human muscle atrophy through different induction methods, such as natural aging, gene editing, nutritional changes, physical activity, chronic wasting diseases, and drug treatments. Common experimental animals include mice, rats, fruit flies, nematodes, and zebrafish, while cellular models are used for more detailed molecular mechanism studies. Various methods have been developed to evaluate muscle atrophy models (Figure 2).

 

1. Animal models (Figure 3)

1.1 Natural aging model

Application: The natural aging model is one of the most commonly used muscle atrophy models, especially for studying sarcopenia. This model observes the natural muscle changes that occur with age in animals, accurately reflecting the physiological changes in muscle atrophy during human aging.

Limitations: It takes a long time to observe significant muscle atrophy, resulting in extended experimental periods and high costs. Additionally, individual differences can lead to inconsistent results.

 

1.2 Gene editing model

Application: gene editing technology can be used to create specific gene mutation mouse models, simulating muscle atrophy caused by accelerated aging or specific genetic defects. These models help study the role of genes in muscle atrophy.

Limitations: Constructing complex gene-edited models requires significant technical and time investment, and some gene mutations may not fully replicate the true nature of human diseases.

 

1.3 Nutritional intervention model

Application: High-fat diet (HFD) induced models are used to study the effects of obesity and related metabolic disorders on muscles. Feeding animals a high-fat diet rapidly induces metabolic syndrome, leading to muscle atrophy. This model is suitable for studying muscle atrophy associated with obesity, insulin resistance, and type 2 diabetes.

Limitations: HFD can cause other complications, such as cardiovascular disease and liver damage, which may interfere with experimental results. Long-term HFD can also alter animal behavior, increasing the complexity of experimental variables.

 

1.4 Physical activity restriction model

Application: Restricting physical activity (e.g., immobilizing limbs or reducing living space) can rapidly induce muscle atrophy, making it suitable for short-term experiments and preliminary screening of drugs or treatments.

Limitations: Physical activity restriction does not fully simulate the natural process of muscle atrophy and may induce stress responses, affecting experimental outcomes.

 

1.5 Disease-induced model

Application: Inducing chronic wasting diseases (e.g., cancer, heart failure) can simulate the process of cachexia and study the impact of systemic inflammation and metabolic imbalance on muscles.

Limitations: Different diseases have complex and diverse pathogenic mechanisms, making it difficult to find a single model that represents all conditions; inducing diseases also poses technical challenges.

 

2. Cellular models (Figure 4)

Application: Culturing myotubes or myoblasts in vitro allows for detailed study of molecular mechanisms within muscle cells, such as protein synthesis and degradation, and signal transduction pathways. These models are suitable for high-throughput drug screening and mechanistic studies.

Limitations: In vitro environments differ significantly from in vivo conditions, and cell behavior in culture dishes may not accurately reflect in vivo scenarios. The lack of complex tissue structures and microenvironments limits their ability to fully simulate real muscle function.

 

3. Small organism models

Application: Using organisms like fruit flies, nematodes, and zebrafish to establish muscle atrophy models offers advantages such as rapid reproduction, low cost, and ease of manipulation, making them suitable for large-scale screening and initial hypothesis testing.

Limitations: These organisms differ significantly from mammals in terms of physiological structure and metabolic pathways, requiring cautious interpretation when applying results to humans.

 

To better understand and manage muscle atrophy, researchers are continuously improving existing models and exploring new modeling methods. By comprehensively evaluating the strengths and weaknesses of different models, scientists aim to identify the most appropriate tools for specific research objectives. These efforts are crucial for advancing the study of muscle atrophy mechanisms and developing effective treatments (Figure 5).Integrating AI and multi-omics approaches will further refine these models, potentially leading to better preventive and therapeutic strategies for patients. Studying muscle atrophy models plays a vital role in promoting healthy aging and reducing the disabilities and dependence associated with sarcopenia and cachexia.

 

This study was co-supervised by Associate Professor Chenyin Fu and Professor Birong Dong (Geriatric Health Care and Medical Research Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University). Gongchang Zhang and Fengjuan Hu reviewed the applications, limitations, and future prospects of muscle atrophy models.

 

See the article: The recent development, application, and future prospects of muscle atrophy animal models 

https://doi.org/10.1002/mef2.70008

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