Mechanisms by which PE21, an extract from the white willow <i>Salix alba</i>, delays chronological aging in budding yeast
Bibliographic record
Abstract
// Younes Medkour 1 , Karamat Mohammad 1 , Anthony Arlia-Ciommo 1 , Veronika Svistkova 1 , Pamela Dakik 1 , Darya Mitrofanova 1 , Monica Enith Lozano Rodriguez 1 , Jennifer Anne Baratang Junio 1 , Tarek Taifour 1 , Paola Escudero 1 , Fani-Fay Goltsios 1 , Sahar Soodbakhsh 1 , Hana Maalaoui 1 , Éric Simard 2 and Vladimir I. Titorenko 1 1 Department of Biology, Concordia University, Montreal, Quebec H4B 1R6, Canada 2 Idunn Technologies Inc., Rosemere, Quebec J7A 4A5, Canada Correspondence to: Vladimir I. Titorenko, email: vladimir.titorenko@concordia.ca Keywords: cellular aging; geroprotectors; lipid metabolism; necrotic cell death; mitochondria Received: July 19, 2019     Accepted: August 27, 2019     Published: October 08, 2019 ABSTRACT We have recently found that PE21, an extract from the white willow Salix alba , slows chronological aging and prolongs longevity of the yeast Saccharomyces cerevisiae more efficiently than any of the previously known pharmacological interventions. Here, we investigated mechanisms through which PE21 delays yeast chronological aging and extends yeast longevity. We show that PE21 causes a remodeling of lipid metabolism in chronologically aging yeast, thereby instigating changes in the concentrations of several lipid classes. We demonstrate that such changes in the cellular lipidome initiate three mechanisms of aging delay and longevity extension. The first mechanism through which PE21 slows aging and prolongs longevity consists in its ability to decrease the intracellular concentration of free fatty acids. This postpones an age-related onset of liponecrotic cell death promoted by excessive concentrations of free fatty acids. The second mechanism of aging delay and longevity extension by PE21 consists in its ability to decrease the concentrations of triacylglycerols and to increase the concentrations of glycerophospholipids within the endoplasmic reticulum membrane. This activates the unfolded protein response system in the endoplasmic reticulum, which then decelerates an age-related decline in protein and lipid homeostasis and slows down an aging-associated deterioration of cell resistance to stress. The third mechanisms underlying aging delay and longevity extension by PE21 consists in its ability to change lipid concentrations in the mitochondrial membranes. This alters certain catabolic and anabolic processes in mitochondria, thus amending the pattern of aging-associated changes in several key aspects of mitochondrial functionality.
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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 | 0.000 | 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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; a candidate call from one teacher head, 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".