Dietary Citrate Restores Age‐Related Endothelial Cell Mitochondrial Dysfunction and Alleviates Atherosclerosis
Bibliographic record
Abstract
ABSTRACT Vascular aging increases the susceptibility to cardio‐cerebrovascular conditions, such as atherosclerotic diseases and hypertension, the leading causes of global disability and mortality. Dietary citrate extends the lifespan of Drosophila melanogaster and Caenorhabditis elegans as well as improves the memory of mice injured by a high‐fat diet (HFD); whether it alleviates vascular aging and age‐related vascular diseases; however, remains unknown. Here, we showed that dietary supplementation of citrate delayed vascular aging, as evidenced by maintaining the integrity of elastic fibers and decreasing the level of the aging‐related marker, CDKN1A (p21). Functionally, citrate improved the sensitivity to endothelial‐dependent vasodilators and lowered blood pressure, and in HFD‐fed ApoE −/− mice, it reduced the size of atherosclerotic plaques, decreased the necrotic core area and vulnerability index in aortic root plaques. Additionally, citrate decreased the frailty index, increased bone density, and improved maximal grip strength and balance speed in both aged and HFD‐fed ApoE −/− mice. Mechanistically, we showed that citrate exposure delayed human umbilical vein endothelial cell senescence with a decreased percentage of cells stained with senescence‐associated β‐galactosidase and p21 levels. Moreover, citrate activated AMPK‐related pathways and reversed senescence‐related mitochondrial dysfunction in basal respiration, maximal respiration, and ATP production and reduced the production of reactive oxygen species (ROS). The citrate‐promoted beneficial effects were abolished due to inactivated AMPK and the increased mitochondrial ROS. Thus, we demonstrate that dietary citrate delays vascular aging and alleviates age‐related vascular diseases by improving mitochondrial function via activation of AMPK‐related pathways. Citrate may have potential clinical implications for interventions against vascular aging and age‐related vascular diseases.
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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 | 0.000 | 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".