FOXO and insulin signaling regulate sensitivity of the circadian clock to oxidative stress
Bibliographic record
Abstract
Circadian rhythms can be regulated by many environmental and endogenous factors. We show here a sensitivity of circadian clock function to oxidative stress that is revealed in flies lacking the foxo gene product. When exposed to oxidative stress, wild-type flies showed attenuated clock gene cycling in peripheral tissues, whereas foxo mutants also lost behavioral rhythms driven by the central clock. FOXO is expressed predominantly in the fat body, and transgenic expression in this tissue rescued the mutant behavioral phenotype, suggesting that foxo has non-cell-autonomous effects on central circadian clock function. Overexpression of signaling molecules that affect FOXO activity, such as the insulin receptor or Akt, in the fat body also increased susceptibility of the central clock to oxidative stress. Finally, foxo mutants showed a rapid decline in rest:activity rhythms with age, supporting the idea that the increase of oxidative stress contributes to age-associated degeneration of behavioral rhythms and indicating the importance of FOXO in mitigating this deterioration. Together these data demonstrate that metabolism affects central clock function and provide a link among insulin signaling, oxidative stress, aging, and circadian rhythms.
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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 | 0.000 |
| 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".