Effects of Circadian Misalignment on Young and Aging Salivary Glands
Bibliographic record
Abstract
Several empirical observations strongly suggest that salivary function is regulated by the circadian clock. Salivary volume, electrolytes levels, and saliva protein composition all show 24-h cycle fluctuations. The exact effects of circadian disruption on salivary gland (SG) physiology and its potential role in salivary pathologies have not been elucidated. Here, we examined the effects of circadian disruption on SG structure, functional gene and protein expression, and immune status using several circadian knockout (KO) mice models where we targeted the following canonical clock genes: brain and muscle ARNT-like 1 protein ( Bmal1 ) KO, Period2 ( Per2 ) KO, Cryptochrome1 ( Cry1 ) KO, Cryptochrome2 ( Cry2 ) KO, and Cryptochrome 1 and 2 double KO ( DKOCry ). All mice were females of young and old age, and data were compared with wild type (control) mice. Our results showed that circadian dysregulation had limited effects on stimulated salivary secretion and SG structure. Yet, circadian disruption significantly affected the expression of several key salivary markers, including mucins, amylase, and aquaporins, in young and aged SGs with increased amylase and acidic mucin production observed in several KO models. In addition, targeting of clock genes has resulted in subtle alterations of the salivary immune microenvironment with increased lymphocyte infiltration and upregulated levels of proinflammatory cytokines. These immune shifts were more pronounced in aged glands with the most proinflammatory phenotypes observed in DKOCry and Bmal1KO mice. Collectively, our results implicate the circadian clock in the intricate temporal regulation governing SG function. Our data also suggest that circadian dysregulation may predispose to increased tissue stress and inflammation. Exploration of salivary system chronobiology represents a new avenue for salivary disease prevention and treatment.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".