Muscle stem cell protein drives repair in aging muscle

Skeletal muscle repair depends on muscle stem cells, called satellite cells, which mature into new muscle fibres after damage or exercise. This process becomes less efficient with age. Researchers published a detailed protein timeline of muscle differentiation in eLife and identified a new key player.

Using mass spectrometry, the researchers tracked more than 6,000 proteins over time as muscle stem cells matured into fully formed muscle cells. One protein stood out: leiomodin 1 (LMOD1). It increased during the early phase of muscle differentiation and was present in muscle stem cells in living mouse muscle tissue.

LMOD1 controls the start of muscle tube formation

Blocking LMOD1 production severely disrupted the formation of myotubes, the precursors of muscle fibres. Conversely, increasing LMOD1 levels accelerated myotube initiation. LMOD1 is an actin nucleator, a protein that helps build actin filaments, the structural elements of the muscle cytoskeleton.

The researchers also found a direct interaction between LMOD1 and the enzyme SIRT1. SIRT1 is a well-known regulator of metabolism and aging, influencing the activity of genes involved in muscle differentiation. LMOD1 affects SIRT1’s location within the cell and the gene activity it controls. Inhibiting SIRT1 partially rescued the impaired differentiation caused by LMOD1 depletion, pointing to a functional link between the two proteins.

Relevance to age-related muscle loss

Muscle loss with aging, known as sarcopenia, is one of the main factors determining independence and health in older adults. The study raises LMOD1 as a potential target for therapies to improve muscle repair. Whether LMOD1 levels actually decline in aging human muscle and contribute to sarcopenia remains to be shown. Current findings are based on mouse models and cell culture experiments.

Read the original article