Characterization of craniofacial tissue aging in genetically diverse HET3 male mice with longevity treatment of 17-alpha estradiol.

Objective: The objective of our study was to 1) characterize craniofacial tissue aging in the new, genetically diverse HET3 mouse model; and 2) ascertain whether increased longevity with 17-alpha estradiol (17αE2) treatment in male mice also improved the health of these tissues. The HET3 mice are a four-strain cross preferred and recommended by the National Institute of Aging to identify longevity treatments and test their ability to reduce age-related pathologies. Previous reports demonstrated increased longevity in male, but not female, HET3 mice with 17αE2 administration.

Design: Male mice were raised to approximately 8 months (young), 16 months (middle-aged), and 25 months (old). Middle-aged and old mice were administered a diet supplemented with 17αE2 for 19 weeks. We quantified craniofacial tissue volume and density changes with micro-computed tomography followed by histology.

Results: Micro-CT showed that the alveolar bone volume and density did not change with age or treatment. Enamel volume and density changed with age but not treatment. Histology revealed region-specific degeneration of periodontal ligaments (PDLs) with age. Cellular cementum demonstrated age-related density decreases but no change in volume. However, cementum volume and density increased with 17αE2 treatment. Dentin volume increased with age whereas density decreased with age, which were attenuated by 17αE2 treatment.

Conclusions: The HET3 mice present an excellent model with which to study the heterogeneous nature of tooth aging and the effects of longevity interventions. We provide novel data on how 17αE2 improves healthspan by modifying age-related changes in the molar dentin and cementum of male mice.