January 13, 2020

Anti-aging drug holds promise for age-related oral diseases

A team led by two UW researchers has found that a transplant drug with anti-aging properties can regenerate bone and decrease gum inflammation, pointing the way toward new treatments for common dental problems in aging patients.

Dr. Jonathan An and Dr. Matt Kaeberlein of the School of Dentistry, along with their colleagues across the country, have been studying rapamycin. Rapamycin is approved by the Food and Drug Administration to prevent organ transplant rejection and has been shown in pre-clinical studies to slow aging and increase lifespan in a variety of species, from worms to mice.

Dr. Jonathan An (left) and Dr. Matt Kaeberlein

Dr. Jonathan An (left) and Dr. Matt Kaeberlein

Until now, however, nobody has explored the effect of rapamycin in the aging mouth. There, people also commonly experience age-related decline and diseases, such as bone loss and gum inflammation leading to periodontal disease.

“As dentists, we see our patients over the span of their life,” said Dr. An, an acting assistant professor of oral health sciences. “As our patients grow older, we as dentists see clinically firsthand the underlying consequences of aging in the mouth, such as increased risk for periodontal disease, root cavities, or low saliva. And many of the treatments we currently provide address the symptoms rather than the underlying cause – which is age. With what we’ve learned about rapamycin, there are a lot of possibilities to look anew at a number of dental conditions.”

These photos show an old mouse before and rapamycin treatment. White arrows indicate areas where there is more bone after rapamycin treatment.

These photos show an old mouse before and after rapamycin treatment. White arrows indicate areas where there is more bone after rapamycin treatment.

In their studies of rapamycin in old mice, the researchers found another intriguing effect: The drug significantly changed the oral microbiome, which is the mouth’s bacterial population. They discovered that old animals not only had a different oral microbiome than the young animals, but that rapamycin treatment reversed changes in the old oral microbiome, making it more similar to what was found in  younger animals.

Dr. Kaeberlein, a biologist who also holds an appointment in the UW School of Medicine as a professor of pathology, is co-director of the Dog Aging Project. where he is investigating rapamycin’s anti-aging properties in companion dogs.

The researchers caution that much work remains to be done before human clinical treatments with rapamycin become a reality. While both male and female mice saw their lifespan extended with rapamycin, the effects are stronger in females than in males. Also, even though the drug is approved for use in humans, the researchers must determine the optimum dosage for bone regeneration or microbiome de-aging, as well as the best mode of application.

The researchers plan to publish their results in a journal and have submitted their manuscript to peer review. In the meantime, the results have been posted on the pre-print server bioRxiv.

“We’re asking ourselves now: What’s happening in the mouth as a function of age, and can we target these biological changes with interventions to extend the oral health span?” Dr. An said. “What makes this so exciting is that we could potentially be supplementing fundamental ideas of oral health, where by targeting the biological aging processes we may be able to provide a unique approach toward prognostics, diagnostics, and even the treatment of age-related dysfunction in our mouths.”