Tissue repair and regeneration after injury slow down with aging. In muscles, this happens because muscle stem cells no longer function properly, making muscle regrowth harder.
A new UCLA study uncovered a cause of this aging-associated dysfunction. The researchers found that these cells choose survival over performance. This ‘survivorship bias’ means the cells manage to stick around, but they lose much of their power to repair muscle.
The study, conducted in mice, reveals that aging muscle stem cells accumulate higher levels of a protein that slows their ability to regrow and repair muscle when needed. Still, there’s a trade‑off: the same protein acts as a shield, helping cells survive in the harsh environment of old tissue.
When scientists compared muscle stem cells from young and old mice, they discovered that a gene called NDRG1 plays a role. In older muscle, this gene’s protein levels were about 3.5 times higher than in young muscle.
Muscles Plays an Important Role in Tissue Regeneration Process
NDRG1 acts like a double‑edged sword in aging muscle. On one hand, it shields stem cells, helping them survive. On the other hand, it works like a brake, slowing down the mTOR pathway that normally sparks cell growth and repair. This slowdown causes stem cells struggle to activate and fix damaged muscle.
Yet when researchers lowered NDRG1 levels, muscle regeneration improved, revealing this gene as a crucial player in how muscles age. This also has a drawback. Without NDRG1’s protection, only a few muscle stem cells survived. As a result, the muscle’s ability to recover after repeated injuries was reduced, indicating that survival and repair are tightly linked in aging tissue.
David Geffen School of Medicine at UCLA said, “The stem cells in young animals are hyper-functioning, really good at what they do, namely sprinting, but they’re not good for the long term. They can make it through the 100-yard dash, but they can’t make it even halfway through the marathon.”
“By contrast, aged stem cells are like marathon runners, slower to respond, but better equipped for the long haul. However, what makes them so proficient over long distances is exactly what renders them poor at sprinting.”
Study sheds light on the biological mechanisms of aging
To confirm their results, the researchers tested muscle stem cells from both young and old mice in the lab and inside living tissue. Across all experiments, the pattern was clear. As NDRG1 levels built up in aging muscle, stem cells became slower at waking up and repairing damage, but they also proved tougher and better at surviving over time.
In simple terms, stem cells that don’t build up enough of the NDRG1 protein eventually die off. What remains is a group of cells that repair muscle more slowly but are tougher and more resilient, able to survive longer in the harsh environment of aging tissue.
The findings could lead to developing therapies that balance stem cell activation with survival, though Rando cautions that “there’s no free lunch. We can improve the function of aged cells for a period of time, for certain tissues, but every time we do this, there’s going to be a potential cost and a potential downside.”
The research team will continue investigating the mechanisms that control the balance between survival and function at the molecular level.
Journal Reference:
Jengmin Kang, Daniel Benjamin, Qiqi Guo et al. Cellular survivorship bias as a mechanistic driver of muscle stem cell aging. Science. DOI: 10.1126/science.ads9175