Teeth do age, becoming more brittle and prone to fracture as the cell populations of the dental pulp become less capable of conducting the necessary maintenance processes. This has only relatively recently become a topic of interest in the dental community, and so relatively little is understood in detail of the mechanisms of tooth aging. Researchers here identify loss of NFATC1 in dental pulp cells as a driver of age-related dysfunction in the maintenance of tooth structural properties, and show that this mechanism is in large part a downstream consequence of the presence of senescent cells in that tissue. Clearance of senescent cells via senolytic therapies reduces the impact of aging on teeth.
Although tooth aging is causally linked to age-associated dental degeneration and regenerative disability, its pathogenesis remains largely unelucidated, despite extensive documentation of its phenotypic alterations. Over time, alongside senescence of the mineralized parenchyma, dental pulp undergoes irreversible changes impairing its renewal capacity. This leads to brittle teeth prone to fracture and susceptible to damage as pulpal degeneration progresses and dentinogenesis fails. These age-related issues remain unresolved due to the unknown drivers. Recognition of this problem in dentistry is relatively recent, dating back only two decades.
There is now growing consensus on the importance of developing methods to counteract tooth aging, particularly pulp aging, as a crucial strategy for tooth conservation. Combining in vivo genetic tools with tissue clearing, advanced 3D imaging, and serial histological and molecular analyses, we identified and validated loss of NFATC1 activity in dental pulp mesenchymal stromal cells (MSCs) as a driver of tooth aging. Induced loss of NFATC1 activity accelerated aging, causing premature tooth aging in young adult mice. Mechanistically, we confirmed it as the cause of age-associated pulpal degeneration and regenerative disability.
Crucially, we demonstrated that senolytics therapeutically ameliorate pulpal degeneration and restore regenerative capacity to preserve vital teeth by eliminating senescent dental pulp MSCs. Similar to reports showing that senescent skeletal stem cells create an inflammatory, degenerative environment impairing skeletal repair in aged bone, our findings demonstrate that driver-induced dental pulp MSC senescence underlies poor regenerative activity in aging teeth.
Link: https://doi.org/10.1016/j.stemcr.2026.102925
View the full article at FightAging
