Conboy says that regulating the TGF-beta pathway may provide a therapeutic possibility for treating age-related muscle disorders. However, she adds that shutting down the pathway altogether may lead to unwanted consequences, such as tumor growth and other side effects. She says that the team’s next goal is to find an appropriate balance between TGF-beta activity and another protein, called Notch, which has previously been shown to successfully rejuvenate old tissue.
Both proteins bind to the same receptors on the surface of stem cells and therefore naturally compete with each other. “In physiologically young animals, Notch is high and TGF-beta is low, and in old animals, it’s the opposite,” says Conboy. “These levels are definitely regulated by the aging process, but we don’t yet know what is the cause.”
Conboy says that this relationship reflects an unfortunate cycle in aging: as levels of Notch drop off with age, TGF-beta is left with ample room to inhibit stem cells, further suppressing the body’s ability to repair damaged tissue. “It’s a self-imposed inhibition of regeneration,” says Conboy.
Michael Rudnicki, director of the Regenerative Medicine Program and the Sprott Centre for Stem Cell Research at the Ottawa Health Research Institute, says that while finding appropriate calibrations may prove challenging, identifying the relationship between Notch and TGF-beta pathways may be a first step in developing therapies for a range of diseases.
Notch and TGF-beta are present in the stem cells of other organs, including the brain, so a similar approach may be a way of repairing tissue in these other organs. “One can think about targets for drug development to reverse or ameliorate many phenomena,” says Rudnicki. “Whether it will reverse aging, I don’t know, but it would be helpful for soft tissue damage or following a stroke.”