Psychological Stress as a Risk Factor for Accelerated Cellular Aging and Cognitive Decline: The Involvement of Microglia-Neuron Crosstalk
Bibliographic record
Abstract
The relationship between the central nervous system (CNS) and microglia is lifelong. Microglia originate in the embryonic yolk sac during development and populate the CNS before the blood-brain barrier forms. In the CNS, they constitute a self-renewing population. Although they represent up to 10% of all brain cells, we are only beginning to understand how much brain homeostasis relies on their physiological functions. Often compared to a double-edged sword, microglia hold the potential to exert neuroprotective roles that can also exacerbate neurodegeneration once compromised. Microglia can promote synaptic growth in addition to eliminating synapses that are less active. Synaptic loss, which is considered one of the best pathological correlates of cognitive decline, is a distinctive feature of major depressive disorder (MDD) and cognitive aging. Long-term psychological stress accelerates cellular aging and predisposes to various diseases, including MDD, and cognitive decline. Among the underlying mechanisms, stress-induced neuroinflammation alters microglial interactions with the surrounding parenchymal cells and exacerbates oxidative burden and cellular damage, hence inducing changes in microglia and neurons typical of cognitive aging. Focusing on microglial interactions with neurons and their synapses, this review discusses the disrupted communication between these cells, notably involving fractalkine signaling and the triggering receptor expressed on myeloid cells (TREM). Overall, chronic stress emerges as a key player in cellular aging by altering the microglial sensome, notably via fractalkine signaling deficiency. To study cellular aging, novel positron emission tomography radiotracers for TREM and the purinergic family of receptors show interest for human study.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".