Stem Cell Insight Turns Back the Clock on Tooth Decay

As people get older, teeth become more fragile and vulnerable to tooth decay. But younger teeth are more resilient. Within teeth are cells called odontoblasts that produce the important structural tissue dentin. Odontoblasts can help restore the integrity of damaged teeth by making more dentin, but this depends on the availability of a ready supply of dental pulp stem cells (DPSCs) to replace the odontoblasts. In older teeth, DPSCs stop working and produce fewer odontoblasts. The factors that change in older teeth and lead to a loss of odontoblasts remain unknown.

Now, researchers from Sichuan University have identified a key biological process underlying tooth aging and have shown a potential way to impede it. They found that a subset of DPSCs missing in older teeth, and a protein they produce, unlocked the regenerative abilities of younger teeth. The new study was published in Stem Cell Reports.¹

How Aging Affects Teeth

The researchers recruited young (aged 18–40) and older (aged 60 and older) volunteers and removed their wisdom teeth. The team had previously reported that DPSCs expressing the protein nuclear factor of activated T cells 1 (NFATC1) were involved in the formation of new dental pulp.²

In the wisdom teeth samples, the researchers found that in stem cell populations derived from older teeth, NFATC1 protein had declined to the point of being undetectable. At the same time, older teeth were more vulnerable to decay. The authors tracked the teeth of volunteers with signs of tooth decay for one year. Older volunteers’ teeth were more likely to show irreversible decay progression over this time.

They then examined DPSCs in mice. Like aged humans, older mice lacked NFATC1-expressing DPSCs.

To study how aging affects DPSCs in mice, the team genetically modified the mice so that they could suppress NFATC1-expressing stem cells in young mice. They saw that the dental pulp of younger mice lacking these cells went into a biological aging process called senescence. The researchers found that this was because NFATC1 was essential for the stem cells’ normal progression through the cell cycle. The dental pulp looked more like that of older mice, lacking odontoblasts. Young teeth lacking these cells were also less able to regenerate after injury.

Drugs Mitigate the Effects of Age-related Changes

But there was good news as well. In young adult mice with injured teeth who lacked the stem cells needed to repair the damage, anti-aging drugs called senolytics helped. The common senolytic drug combination—the cancer drug dasatinib with the plant pigment quercetin—removed cells undergoing senescence in the mice’s teeth. This helped restore levels of dentin formation to levels seen in control mice. The senolytics also improved dental pulp density and reduced the porosity of the mice’s teeth.

The team acknowledged that there were some limitations to their study. Only a small number of volunteers were recruited for the tooth analysis—just three per study arm—and the mouse model isn’t a perfect replica of natural aging. Still, the researchers wrote in the paper, “These findings advance our understanding of tooth aging and provide potential strategies for combating age-related dental decline.”