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Longevity Briefs: How Is Injured Muscle Repaired?

Posted on 1 November 2021

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Muscle fibres are the contractile cells of muscle tissue, each one a single cell many centimetres long and with many DNA-containing nuclei. Recovering from severe muscle injury requires the formation of new muscle fibres from muscle stem cells in order to replace those that have been destroyed. However, individual muscle fibres frequently sustain mild damage during exercise, which needs to be repaired. Such repeated damage and repair is not detrimental – in fact, it seems to be necessary for the maintenance and growth of muscle tissue. Unfortunately, we don’t really understand enough about how this whole process works, and why repeated repair builds stronger and stronger muscle.

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Contractile muscle tissue is made up of bundles of muscle fibres, each of which is a single cell containing many nuclei. Within each muscle fibre are many myofibrils containing the sarcomeres – the molecular structures responsible for producing the force during muscle contraction.

What did the researchers do: Here, researchers designed experiments to study in detail the molecular events occurring within hours of muscle fibre injury. They first studied muscle repair in mice and muscle biopsies from humans who had just undergone acute exercise. They also studied the later phases of muscle repair in myotubes – these are cells similar to muscle fibres that are formed in cell culture when muscle precursor cells, called myoblasts, fuse together to form one long cell.

Key takeaway(s) from this research: The researchers found that muscle repair was broadly organised into two phases. Beginning almost immediately after injury, there is an initial resealing phase in which the muscle fibre begins to repair any tears in its membrane. The breach is patched up by a protein cap made mainly from annexins, which are a group of proteins that bind other proteins to the cell membrane. Later, ‘scars’ form containing structural proteins and heat shock proteins (which help cells resist environmental stress).

Muscle fibre resealing and rebuilding following an injury.

Following the initial resealing phase, the muscle cells begin to clean up internal sites of damage and to repair the sarcomeres (the molecular structures which are responsible for producing the force during muscle contraction). Researchers found that the DNA-containing nuclei in the muscle fibres and myotubes actually moved closer to the sites of injury, allowing the cell to conduct on-site manufacture of proteins needed for repair. Messenger RNAs, including those coding for the structural and heat-shock proteins mentioned earlier, were found in high quantities close to the repair sites. Finally, the researchers also found that mitochondria (the cell’s ‘power plants’) are also heavily involved in the repair process. Muscle fibres need calcium to contract, which is stored in a compartment within the cell. When muscle fibres are damaged, this calcium builds up at the site of injury as it leaks from stores and from outside the cell. Mitochondria within the muscle fibres were able to migrate toward the sites and sequester away the excess calcium, helping to prevent a harmful build-up. After 24 hours, repair of the sarcomeres was almost complete.

These findings improve our understanding of how individual muscle fibres repair themselves, and also help identify some potential targets to improve muscle repair. For example, the researchers identified a signalling cascade that is required for the movement of the nuclei toward the site of injury. By targeting components of this pathway, perhaps we could enhance muscle repair.

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