Lithocholic acid delays yeast aging by altering mitochondrial dynamics
Bibliographic record
Abstract
We found that an exogenously added bile acid called lithocholic acid (LCA) delays yeast aging and accumulates in the inner mitochondrial membrane (IMM). To define the mechanism by which LCA extends yeast longevity, we 1) examined how LCA influences mitochondrial proteome and lipidome; 2) investigated the effect of LCA on the composition and stoichiometry of respiratory complexes and supercomplexes in the IMM; 3) assessed how LCA affects mitochondrial oxygen consumption, membrane potential and reactive oxygen species (ROS); 4) examined how LCA influences mitochondrial morphology and how it affects the chronology of events characteristic of age‐related, mitochondria‐controlled apoptosis; and 5) investigated the effect of LCA on the lifespans of long‐ and short‐lived mutants lacking individual components of the mitochondrial fission and fusion machines. Our findings imply that LCA delays yeast aging by increasing the level of phosphatidylserine (PS) and decreasing the levels of phosphatidylethanolamine (PE) and cardiolipin in the IMM. By altering the abundance of these lipid species, LCA greatly expands mitochondrial membrane cristae. In addition, LCA enhances the positive effect of PS and weakens the negative effect of PE on membrane protein machines whose activity they modulate – thereby 1) stimulating protein machines driving mitochondrial respiration, the maintenance of mitochondrial membrane potential and ROS homeostasis, mitochondrial fusion, and protein synthesis in mitochondria; and 2) inhibiting protein machines promoting mitochondrial fission and mitochondria‐controlled apoptosis. Supported by NSERC of Canada.
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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".