Over time, muscle stem cells are less reparative but more resistant

Ageing slows down tissue repair and regeneration following injury. This occurs in muscles because the muscle stem cells are no longer functioning properly.

UCLA researchers have identified the cause for this age-related dysfunction. Researchers found that the cells prioritize survival over performance. The cells are able to survive, but their ability to repair muscles is greatly diminished.

This study in mice reveals that older muscle stem cells have higher levels of protein, which slows down their ability to regenerate and repair muscles when necessary. The same protein also acts as a protective shield to help cells endure the harsh conditions of old tissue.

Scientists discovered that NDRG1 is involved in the differentiation of muscle stem cells between young and older mice. The protein levels of this gene were 3.5 times greater in older muscle than they were in younger muscle.

The role of muscle in tissue regeneration

NDRG1 is a two-edged blade in aging muscles. It shields stem cell, which helps them to survive. It also acts like a brake by slowing the mTOR pathways that are normally responsible for cell repair and growth. The stem cells are unable to repair damaged muscles because of this slowdown.

Researchers found that lowering NDRG1 levels improved muscle regeneration, demonstrating this gene’s role in the ageing of muscles. There is a downside to this. Without NDRG1 protection, few stem cells of muscle survived. The muscle was less able to heal after multiple injuries, which indicates that repair and survival are closely linked.

David Geffen School of Medicine, UCLA. The stem cells of young animals perform well, are good sprinters, but not for long-term use. “They can run the 100 yard dash but not even half the marathon.”

The stem cells of older people are more like marathoners, who may be slower, but have better endurance. What makes them good at long distances, is also what makes them bad sprinters.

A study sheds new light on biological mechanisms that age us

Researchers tested stem cells in living tissues and labs to confirm their findings. The pattern was consistent across all tests. NDRG1 builds up over time in aging muscles, causing stem cells to become slower and less able to repair damage. However, they are also more resilient and successful at surviving.

Simple: stem cells which do not produce enough NDRG1 eventually go extinct. The cells left behind are stronger and tougher, capable of withstanding the harsh conditions of old tissue.

Rando warns, however, that the findings may lead to therapies that balance stem cells activation and survival. There’s no such thing as a free lunch. “We can enhance the functionality of old cells, in certain tissues for a short period, but there will be costs and potential negative effects.”

The team of researchers will investigate the mechanisms at the cellular level that regulate the balance between survival, function and the ability to survive.

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