Rolling back the clock on muscle disease, aging

Last week CIRM grantees at University of California Berkeley published a follow-up to some of my favorite stem cell research. I'm speaking personally here as a runner who is getting older and would like to turn my race recovery back to what it was in my youth.

Irina Conboy started investigating the slow response of aging muscle stem cells as a postdoctoral fellow in the lab of Thomas Rando at Stanford University (I've written about that work here). What they found is that older muscles in mice don't respond very effectively to muscle damage. But, and this is a big but, if those older mice have younger blood, the muscle stem cells work just fine. Strange, but true.

Since that discovery, Conboy and her lab at Berkeley has been piecing together the story of how and why the younger blood refreshes those old and tired muscle stem cells. In their latest work, which was published in the journal Chemistry & Biology, they show a way using a short-term dose of chemicals to roll back the clock on mature muscle and return it to an earlier state.

A press release from UC Berkeley says:

Building new muscle to replace old or damaged tissue is the routine job of muscle stem cells, or satellite cells. Stationed along the perimeter of adult muscle tissue, they wait for a signal to grow, divide and fuse into new muscle fibers when there’s damage to repair.

But that repair process gets worn out in people with Duchenne muscular dystrophy, a genetic condition in which muscles degenerate because of a defective structural protein and subsequent exhaustion of muscle stem cells. Muscle repair also becomes incapacitated with advancing age.

The group hopes that by turning back the clock, they can return the muscle to a state where it is better able to repair damage. The press release goes on to say:

The researchers say the next steps include testing the process on human muscle tissue and screening for other molecular compounds that could help de-differentiate mature tissue.

“This approach won’t work for all degenerative diseases,” said Conboy. “It might work for some diseases or conditions where we can start with differentiated tissue, such as neurons or liver cells. But patients with type I diabetes, for instance, lack the pancreatic beta-islet cells to produce insulin, so there is no functional differentiated tissue to start with. Our approach is not a replacement for pluripotent cells, but it’s an additional tool in the arsenal of stem cell therapies.”

The group is a long way from marketing the next race recovery beverage. They still have to show that the technique works in human muscle and that those more youthful cells are better able to repair damage.

CIRM Funding: Irina Conboy (RN1-00532-1)
Chemistry & Biology, September 23, 2011


A.A.