NFATC1 dysfunction-triggered MSC senescence induces tooth aging amenable to senolytic therapy

Area of Science:

• Gerontology
• Dental Biology
• Regenerative Medicine

Background:

• Tooth aging mechanisms remain largely unexplored due to unique dental tissue characteristics.
• Understanding organ-specific aging drivers is crucial for combating age-related decline.
• Mammalian teeth have distinct features like cell-free calcified parenchyma and limited turnover.

Purpose of the Study:

• To identify the in vivo driver of tooth aging.
• To elucidate the mechanisms underlying age-related dental degeneration and regenerative decline.
• To explore senolytic therapy as a strategy for tooth preservation.

Main Methods:

• Analysis of clinical data from human tooth aging.
• Development and application of genetic tools: Cre-based pulse-chase tracing and ablation, gene manipulation with tracing, and fluorescent ubiquitination-based cell cycle indicator (FUCCI).
• In vivo driver identification and senescence induction in dental pulp mesenchymal stromal cells (MSCs).

Main Results:

• The first in vivo driver of tooth aging was identified.
• This driver induces senescence in dental pulp mesenchymal stromal cells (MSCs), explaining age-related degeneration.
• Senolytic therapy effectively reversed aging phenotypes and restored dental repair capacity.

Conclusions:

• Discovered a novel in vivo driver of tooth aging and its role in MSC senescence.
• Senolytic therapy shows promise for ameliorating tooth aging and restoring regenerative function.
• Findings provide new strategies for preserving tooth health during aging.