Increased chromatin accessibility underpins senescence
Bibliographic record
Abstract
Senescence is a cellular state induced by various stressors or extracellular signals, but a universal pathway that triggers this process irrespective of the initial stressor has yet to be identified. Recent data indicate that chromatin opening, particularly in the noncoding genome, is a hallmark of cellular senescence. We propose a model in which this increased chromatin accessibility mediated by transcription factors downstream of the senescence-inducing stressors acts as a decisive factor to commit cells toward the senescence fate. Engagement toward senescence is then determined by the balance between mechanisms that increase or decrease chromatin accessibility and can be influenced by modulating the activity of specific histone-modifying complexes. Traits of senescent cells, such as increased nuclear and nucleolar size, the secretion of pro-inflammatory cytokines, reduced rRNA biogenesis, telomere dysfunction, expression of retrotransposons and endogenous retroviruses, as well as DNA damage, can all be attributed to increased chromatin accessibility. This concept suggests potential targets to tilt the balance toward the senescence response in the context of future therapies against cancer and age-related diseases.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".