A study by Stanford Medicine researchers in older mice may lead to treatments that help seniors regain muscle strength lost to aging.

Muscle stem cells—activated in response to muscle injury to regenerate damaged muscle tissue—lose their potency with age. A study from the National Health and Nutrition Examination Survey found that 5 percent of adults aged 60 and over had weak muscle strength, and 13 percent had intermediate muscle strength. 

Now, researchers at Stanford Medicine are seeing that old mice regain the leg muscle strength of younger animals after receiving an antibody treatment that targets a pathway mediated by a molecule called CD47.  

The study was published in Cell Stem Cell and is co-funded by the California Institute for Regenerative Medicine (CIRM).  

A Closer Look at CD47 

CD47 is a protein found on many cell surfaces. Known as the “don’t eat me” signal, it helps cancer cells evade immune attack. Stanford researchers now find that aged muscle stem cells may use a similar strategy.

It has been hard to determine why muscle stem cells divide more slowly with age. Dr. Ermelinda Porpiglia used single‑cell mass cytometry to study mouse muscle stem cells and focused on CD47. She found high CD47 levels on stem cells from older mice, but much lower levels in younger animals. High CD47 also correlated with reduced stem cell function.

“This finding was unexpected because we think of CD47 mainly as an immune regulator,” Porpiglia said. “But it makes sense that, like cancer cells, aged stem cells might use CD47 to escape the immune system.”

Testing an Antibody 

Further investigation showed that thrombospondin, which binds to CD47 on muscle stem cells, suppresses their activity.
Porpiglia used an antibody that blocks thrombospondin from binding CD47 and saw dramatic effects. Stem cells from older mice divided more robustly in the lab, and older mice injected with the antibody developed larger, stronger leg muscles than controls.

When given before injury, the antibody also helped aged mice recover more like young animals.

“We hope it may one day be possible to inject a thrombospondin‑blocking antibody at specific sites to regenerate muscle in older people or treat damage from disease or surgery,” Porpiglia said.

These results are significant because they could eventually help improve muscle recovery after surgery and slow age‑related muscle decline. But more research is needed.

“Rejuvenating muscle stem cells in older mice produced a significant strength increase,” said senior author Dr. Helen Blau. “This localized treatment could be useful clinically, though we still need to determine safety and effectiveness in humans.”

CIRM has previously funded work with researchers using CD47 that led to clinical trials targeting cancer. You can read about that work here and here. That work led to the creation of a company, Forty Seven Inc., which Gilead eventually bought for $4.9 billion.  

Read the original release by Krista Conger on the Stanford Medicine website.