Sex Difference in Daily Rhythms of Clock Gene Expression in the Aged Human Cerebral Cortex
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Bibliographic record
Abstract
Studies using self-report and physiological markers of circadian rhythmicity have demonstrated sex differences in a number of circadian attributes including morningness-eveningness, entrained phase, and intrinsic period. However, these sex differences have not been examined at the level of the molecular clock and not in human cerebral cortex. The authors tested the hypothesis that there are detectable daily rhythms of clock gene expression in human cerebral cortex and that there are significant sex differences in the timing of these rhythms. The expression levels of 3 clock genes-PER2, PER3, and ARNTL1-were quantified in samples of dorsolateral prefrontal cortex from 490 deceased individuals in 2 cohort studies of older individuals, the Religious Orders Study and the Rush Memory and Aging Project, using mRNA microarray data. Clock gene expression at death was parameterized as a function of time of death using cosine curves and was examined for sex differences in the phase of these curves. Significant daily variation was seen in the expression of PER2 (p = 0.004), PER3 (p = 0.003), and ARNTL1 (p = 0.0005). PER2/3 expression peaked at 10:38 (95% confidence interval [CI], 09:20-11:56) and 10:44 (95% CI, 09:29-11:59), respectively, and ARNTL1 expression peaked in antiphase to this at 21:23 (95% CI, 20:16-22:30). The timing of the expression of all 3 genes was significantly earlier in women than in men (PER2 6.8 h, p = 0.002; PER3 5.5 h, p = 0.001; ARNTL1 4.7 h, p = 0.007). Daily rhythms of clock gene expression are present in human cerebral cortex and can be inferred from postmortem samples. Moreover, these rhythms are relatively delayed in men compared with women.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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 it