Alpha cell inflammation during human pancreas aging and type 2 diabetes and its reversal by calorie restriction in mice
Bibliographic record
Abstract
Abstract Aging increases risk for type 2 diabetes (T2D), partly through loss of beta cell identity and function driven by metabolic stress and islet inflammation. While calorie restriction (CR) promotes beta cell longevity in young animals, its impact on cellular aging and inflammatory burden in older individuals is unclear. Using SCENIC regulon and multiomic analyses, we find that aging human alpha cells adopt a coordinated inflammatory phenotype marked by IFN-γ signaling to increase major histocompatibility complex (MHC) class I presentation, and CD8 + T cell recruitment and activation towards islets. In T2D, CD8 + T cells further progress towards an effector memory state. CR reduces alpha cell MHC-I expression while subsequently suppressing CD8 + effector status and accompanied by reduced islet inflammation and immune cell infiltration in mice. Together, these findings highlight an alpha cell–immune signaling axis in aging and T2D that may underlie fibrosis and disease pathophysiology.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".