Using a combination of chemical and systems biological approaches for defining a mechanism by which a novel anti‐aging compound greatly extends yeast longevity
Bibliographic record
Abstract
We use the yeast Saccharomyces cerevisiae as a model to for unveiling the mechanisms of cellular aging in multicellular eukaryotes. Our findings imply that the chronological aging of yeast is a developmental program that progresses through two checkpoints. Implementing our understanding of longevity regulation, we used a custom‐designed screen of extensive compound libraries for identifying 25 novel anti‐aging compounds that extend yeast longevity. Using a combination of proteomic, lipidomic, metabolomic, and systems biological approaches, we established the molecular and cellular mechanisms underlying the life‐extending ability of one of these compounds, called LA. Our findings imply that LA extends yeast longevity by 1) activating mitochondrial fusion, thereby abolishing age‐related, mitochondria‐controlled apoptosis; 2) modulating mitochondrial production of reactive oxygen species, thereby activating expression of a compendium of stress response genes; 3) remodeling lipid metabolism in the endoplasmic reticulum, lipid bodies, and peroxisomes, thereby greatly delaying age‐related necrosis caused by the buildup of free fatty acids; and 4) modulating a non‐nuclear node of the protein kinase A‐governed glucose signaling network controlled by the protein kinase Rim15p. Importantly, LA has a similar effect on some of these longevity‐and disease‐related processes in cultured human cells.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 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".