Transcription factors <scp>CEP</scp>‐1/p53 and <scp>CEH</scp>‐23 collaborate with <scp>AAK</scp>‐2/<scp>AMPK</scp> to modulate longevity in Caenorhabditis <i>elegans</i>.
Bibliographic record
Abstract
A decline in mitochondrial electron transport chain (ETC) function has long been implicated in aging and various diseases. Recently, moderate mitochondrial ETC dysfunction has been found to prolong lifespan in diverse organisms, suggesting a conserved and complex role of mitochondria in longevity determination. Several nuclear transcription factors have been demonstrated to mediate the lifespan extension effect associated with partial impairment of the ETC, suggesting that compensatory transcriptional response to be crucial. In this study, we showed that the transcription factors CEP-1/p53 and CEH-23 act through a similar mechanism to modulate longevity in response to defective ETC in Caenorhabditis elegans. Genomewide gene expression profiling comparison revealed a new link between these two transcription factors and AAK-2/AMP kinase (AMPK) signaling. Further functional analyses suggested that CEP-1/p53 and CEH-23 act downstream of AAK-2/AMPK signaling and CRTC-1 transcriptional coactivator to promote stress resistance and lifespan. As AAK-2, CEP-1, and CEH-23 are all highly conserved, our findings likely provide important insights for understanding the organismal adaptive response to mitochondrial dysfunction in diverse organisms and will be relevant to aging and pathologies with a mitochondrial etiology in human.
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How this classification was reachedexpand
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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
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".