Age‐dependent activation of lympho‐endothelial interactions in mice
Bibliographic record
Abstract
The endothelium‐dependent dilation to acetylcholine decreases with age suggesting an endothelial dysfunction. This could lead to leukocyte activation and contribute to the worsening of the vascular dysfunction. We raised the hypothesis that lymphocyte adhesion to the native endothelium is increased in aging mice and is associated with a change in lymphocyte adhesion molecule expression. The aorta and lymphocytes were isolated from 3 month old (m/o) and 12 m/o male C57Bl/6 mice. Radiolabeled lymphocytes were allowed to adhere onto the native endothelium ex vivo . The expression of the adhesion molecules (CD18 and CD62L) was studied by flow cytometry. At 12 months, lymphocyte adhesion (lymphocytes/mm 2 ) was increased (206±19, n=12; P<0.05) compared to 3 months (126±10, n=28). At 3 months, lymphocyte adhesion was significantly increased (P<0.05) after endothelial stimulation by thrombin (20 U, 200±28, n=5) or histamine (0.1 μM, 219±43, n=5). At 12 months, endothelial stimulation failed to further increase lymphocyte adhesion. However, we observed an increased (P<0.05) expression of CD18 and an enhanced shedding of CD62L in lymphocytes isolated from 12 m/o mice. Treatment with PMA (10 μM) mimicked the effect of aging in lymphocytes isolated from 3 m/o mice by shedding of CD62L, while PMA had no effect at 12 months. Finally, the adhesion of 12 m/o lymphocytes onto 3 m/o aortic segments was increased (226±17, n=6; P<0.05) to a similar level when 3 (250±20, n=3) m/o lymphocytes were incubated onto the endothelium of aortic segments isolated from 12 m/o mice. These results indicate that aging is associated with both lymphocyte and endothelial dysfunction that lead to increased lymphocyte adhesion. This work is supported by the Canadian Institutes of Heath Research.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".