By increasing the level of cardiolipin in the inner mitochondrial membrane, a novel anti‐aging small molecule modulates many longevity‐ and disease‐related processes in mitochondria
Bibliographic record
Abstract
We use the yeast Saccharomyces cerevisiae as a model to study the mechanisms by which age‐related changes in mitochondrial membrane lipids regulate longevity. We identified a novel anti‐aging small molecule, called LA, which increases the concentration of cardiolipin (CL) in the inner mitochondrial membrane. We: 1) assessed the effect of LA on the life spans of long‐ and short‐lived mutants lacking components of the mitochondrial fission, fusion, and tubulation machines or mitochondrial components involved in the biosynthesis of CL and phosphatidylethanolamine (PE); 2) examined how LA influences the chronology of numerous events characteristic of age‐related, mitochondria‐controlled apoptosis; 3) investigated the effect of LA on the susceptibility of yeast to exogenous pro‐apoptotic compounds targeting mitochondria; and 4) assessed the effect of LA on the age‐dependent dynamics of changes in mitochondrial oxygen consumption, membrane potential, and reactive oxygen species (ROS) generation. Our findings imply that: 1) by increasing CL stability and decreasing the “PE/CL” ratio within the mitochondrial membrane, LA specifically reorganizes the protein machines involved in mitochondrial fusion, fission, apoptosis, respiratory chain, and ROS production, thereby delaying aging; and 2) LA can be used for manipulating mitochondrial dysfunction in aging, neurodegeneration and cardiomyopathy.
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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".