Chronic muscle weakness and mitochondrial dysfunction in the absence of sustained atrophy in a preclinical sepsis model

eLife, 2019 · DOI: https://doi.org/10.7554/eLife.49920.001 · Published: December 3, 2019

Simple Explanation

Sepsis survivors often experience chronic physical weakness and fatigue. This study aimed to understand the long-term effects of sepsis on muscle function using a mouse model with ICU-like interventions. The researchers found that sepsis survivors had muscle mass recovery, but the quality of their muscle fibers had worsened. Specifically, abnormalities were observed in mitochondria, which are responsible for powering cells. The study suggests that improving muscle quality, such as through antioxidant therapies, could be a potential treatment avenue for sepsis survivors, beyond just increasing muscle quantity.

Study Duration

1 month

Participants

Middle-aged C57BL/6 mice

Evidence Level

Level 2: Experimental study - Murine model

Key Findings

1
Sepsis survivors exhibit chronic muscle weakness for at least one month, even after muscle mass recovery.
2
Muscle weakness is associated with impaired mitochondrial activity, including abnormal ultrastructure and reduced respiration.
3
Persistent protein oxidative damage is evident in the muscle of sepsis survivors, suggesting ongoing cellular stress.

Research Summary

This study establishes a murine model of sepsis with ICU-like interventions to investigate chronic muscle weakness in survivors. The research demonstrates that sepsis survivors have prolonged muscle weakness independent of muscle atrophy, linked to mitochondrial dysfunction and oxidative damage. The findings suggest that therapeutic strategies should focus on restoring mitochondrial health and addressing muscle quality, not just increasing muscle mass.

Practical Implications

Therapeutic Development

Focus on therapies that improve mitochondrial function and reduce oxidative stress in muscles, such as antioxidant treatments.

Rehabilitation Strategies

Incorporate exercises and interventions that enhance muscle quality and mitochondrial health, in addition to traditional muscle strengthening exercises.

Clinical Monitoring

Monitor sepsis survivors for signs of mitochondrial dysfunction and oxidative damage to tailor interventions and improve long-term outcomes.

Study Limitations

1
The study is based on a murine model, which may not fully replicate the complexity of human sepsis.
2
The study focused on a specific age group (middle-aged mice), and results may not be generalizable to all age groups.
3
Further research is needed to elucidate the precise mechanisms linking mitochondrial dysfunction, oxidative damage, and muscle weakness in sepsis survivors.

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