Sex differences and age-related changes in the mandibular alveolar bone mineral density using a computer-aided measurement system for intraoral radiography.

This study aimed to conduct a cross-sectional data analysis of the alveolar bone mineral density (al-BMD) in 225 patients of various ages and different sexes. The al-BMD value in the mandibular incisor region was calculated using a computer-aided measurement system (DentalSCOPE) for intraoral radiography. All participants with intact teeth (101 males and 124 females; age range, 25-89 years) were divided into three age-segregated groups (25-49, 50-74, and > 75 years). Statistical differences were evaluated using the Mann-Whitney U or Kruskal-Wallis test. Males exhibited significantly greater al-BMD than females (p < 0.001). The highest means were observed in the 25-49 age group, regardless of sex (1007.90 mg/cm2 in males, 910.90 mg/cm2 in females). A 9.8% decrease in al-BMD was observed with the increase in age in males (25-49 to 50-74 years; p = 0.004); however, no further changes were seen thereafter. In females, a decreasing trend was seen throughout the lifespan, with values reaching up to 76.0% of the initial peak value (p < 0.001). Similar to other skeletal sites, the alveolar bone exhibits sex differences and undergoes a reduction in BMD via the normal aging process.

Comprehensive Analysis Identified the Circadian Clock and Global Circadian Gene Expression in Human Corneal Endothelial Cells.

Purpose: To investigate circadian clock oscillation and circadian global gene expression in cultured human corneal endothelial cells (cHCECs) to elucidate and assess the potential function of circadian regulation in HCECs. Methods: In this study, we introduced a circadian bioluminescence reporter, Bmal1:luciferase (Bmal1:luc), into cHCECs and subsequently monitored real-time bioluminescence rhythms. RNA-sequencing data analysis was then performed using sequential time-course samples of the cHCECs to obtain a comprehensive understanding of the circadian gene expression rhythms. The potential relevance of rhythmically expressed genes was then assessed by systematic approaches using functional clustering and individual gene annotations. Results: Bmal1:luc bioluminescence exhibited clear circadian oscillation in the cHCECs. The core clock genes and clock-related genes showed high-amplitude robust circadian messenger RNA (mRNA) expression rhythms in cHCECs after treatment with dexamethasone, and 329 genes that exhibited circadian mRNA expression rhythms were identified (i.e., genes involved in various physiological processes including glycolysis, mitochondrial function, antioxidative systems, hypoxic responses, apoptosis, and extracellular matrix regulation, which represent the physiological functions of HCECs). Conclusions: Our findings revealed that cHCECs have a robust and functional circadian clock, and our discovery that a large number of genes exhibit circadian mRNA expression rhythms in cHCECs suggests a potential contribution of circadian regulation to fine-tune HCEC functions for daily changes in the environment.

Quantitative morphometric analysis of molar teeth and alveolar bone using micro-computed tomography in aged mice.

OBJECTIVES: Irreversible morphological regressions of the teeth or related structures in older people can diminish their overall health. However, research on human aging in dentistry is complicated by several confounding factors. In this study, we conducted a morphometric analysis of the mandibular second molars and surrounding alveolar bone in C57BL/6 mice to evaluate age-related changes in the oral cavity. METHODS: The animals were divided into five groups based on their age: 4 weeks (juvenile mice; n = 5); 20 weeks (n = 7), 50 weeks (n = 5), 77 weeks (n = 7), and 100 weeks (n = 5); changes were evaluated using micro-computed tomography. RESULTS: The molars of juvenile mice had sharp and pointed cusps and presented maximum heights. With age and occlusal wear, the cusp heights demonstrated a significant decrease (up to 75%) until the last stage of life. Conversely, apparent lesions were not observed on the basal portion of the crown, even in the most heavily worn teeth. The roots of the molars continued to grow in length at 4 weeks of age. Alveolar bone resorption begins to occur in middle age and continues throughout life. The proportion of vertical bone loss reached approximately 40% of the entire root length, demonstrating a remarkable increase between weeks 77 and 100. CONCLUSIONS: Overall, these morphological changes were similar to those observed in humans. Therefore, it might be appropriate to use aged mice as an experimental model for basic and clinical research in geriatric dentistry.

Chronic circadian misalignment accelerates immune senescence and abbreviates lifespan in mice.

Modern society characterized by a 24/7 lifestyle leads to misalignment between environmental cycles and endogenous circadian rhythms. Persisting circadian misalignment leads to deleterious effects on health and healthspan. However, the underlying mechanism remains not fully understood. Here, we subjected adult, wild-type mice to distinct chronic jet-lag paradigms, which showed that long-term circadian misalignment induced significant early mortality. Non-biased RNA sequencing analysis using liver and kidney showed marked activation of gene regulatory pathways associated with the immune system and immune disease in both organs. In accordance, we observed enhanced steatohepatitis with infiltration of inflammatory cells. The investigation of senescence-associated immune cell subsets from the spleens and mesenteric lymph nodes revealed an increase in PD-1+CD44high CD4 T cells as well as CD95+GL7+ germinal center B cells, indicating that the long-term circadian misalignment exacerbates immune senescence and consequent chronic inflammation. Our results underscore immune homeostasis as a pivotal interventional target against clock-related disorders.

REV-ERBα and REV-ERBß function as key factors regulating Mammalian Circadian Output.

The circadian clock regulates behavioural and physiological processes in a 24-h cycle. The nuclear receptors REV-ERBα and REV-ERBß are involved in the cell-autonomous circadian transcriptional/translational feedback loops as transcriptional repressors. A number of studies have also demonstrated a pivotal role of REV-ERBs in regulation of metabolic, neuronal, and inflammatory functions including bile acid metabolism, lipid metabolism, and production of inflammatory cytokines. Given the multifunctional role of REV-ERBs, it is important to elucidate the mechanism through which REV-ERBs exert their functions. To this end, we established a Rev-erbα/Rev-erbß double-knockout mouse embryonic stem (ES) cell model and analyzed the circadian clock and clock-controlled output gene expressions. A comprehensive mRNA-seq analysis revealed that the double knockout of both Rev-erbα and Rev-erbß does not abrogate expression rhythms of E-box-regulated core clock genes but drastically changes a diverse set of other rhythmically-expressed output genes. Of note, REV-ERBα/ß deficiency does not compromise circadian expression rhythms of PER2, while REV-ERB target genes, Bmal1 and Npas2, are significantly upregulated. This study highlight the relevance of REV-ERBs as pivotal output mediators of the mammalian circadian clock.

Incremental Growth Lines in Mouse Molar Dentin Represent 8-hr Ultradian Rhythm.

Rhythmic incremental growth lines occur in dental hard tissues of vertebrates, and dentinogenesis in rodent incisors is suggested to be controlled by the 24-hr circadian clock. Rodent incisors continue to grow throughout the animal's life; however, similar to human teeth, rodent molars stop growing after crown formation. This similarity suggests that the mouse molar is an excellent model to understand the molecular mechanisms underlying growth of human teeth. However, not much is known about the rhythmic dentinogenesis in mouse molars. Here, we investigated the incremental growth lines in mouse molar dentin using tetracycline as the growth marker. The incremental growth lines were observed to be generated at approximately 8-hr intervals in wild-type mice housed under 12:12 hr light-dark conditions. Moreover, the 8-hr rhythmic increments persisted in the wild-type and Bmal1-/- mice housed in constant darkness, where Bmal1-/- mice become behaviorally arrhythmic. These results revealed that the dentinogenesis in mouse molars underlie the ultradian rhythms with around 8-hr periodicity. Further, the circadian clock does not seem to be involved in this process, providing new insight into the mechanisms involved in the tooth growth.