We age, in part because our adult stem cells fail to replace the damaged cells in the tissues. This happen mainly because the stem cells are surrounded by chemicals that prevent them to function normally. Recently, researchers at the University of California, Berkeley, have discovered a small-molecule drug that could “rejuvenate” brain and muscle tissue. This drug inhibits the activity of a growth factor called TGF-beta 1, which has been previously shown to affect a stem cell’s ability to regenerate.
"We established that you can use a single small molecule to rescue essential function in not only aged brain tissue but aged muscle," said co-author David Schaffer, director of the Berkeley Stem Cell Center and a professor of chemical and biomolecular engineering. "That is good news, because if every tissue had a different molecular mechanism for aging, we wouldn't be able to have a single intervention that rescues the function of multiple tissues."
Researchers showed that TGF-beta 1 levels in the bloodstream tend to increase with age in all tissues of the body, decreasing this way the ability of stem cell to regenerate. Using a viral vector developed for gene therapy, the team inserted genetic blockers into the brains of old mice to knock down TGF-beta1 activity, and found enhanced tissue regeneration in the old mice’s brains.
In the new study the team injected a small molecule called Alk5 kinase inhibitor into the blood of old mice once a day for 11 days. The Alk5 kinase inhibitor is a chemical that blocks the TGF-beta1 receptor and thus reduces the effect of TGF-beta1. Researchers found that the small molecule successfully renewed stem cell function in both brain and muscle tissue of the same old animal, potentially making it stronger and more clever.
Researchers hope this research could result in effective treatments for combating multiple age-related degenerative disorders, which can have a range of debilitating effects.
"The challenge ahead is to carefully retune the various signaling pathways in the stem cell environment, using a small number of chemicals, so that we end up recalibrating the environment to be youth-like," Conboy said. "Dosage is going to be the key to rejuvenating the stem cell environment."