SASP-Mediated Cholinergic Synapse Disruption

**Molecular Mechanism and Rationale** The senescence-associated secretory phenotype (SASP) represents a fundamental shift in microglial function that directly undermines cholinergic neurotransmission through extracellular matrix degradation. Senescent microglia, characterized by elevated p16^INK4A and p21^CIP1 expression alongside telomere shortening, undergo dramatic transcriptional reprogramming driven by NF-κB and C/EBPβ signaling cascades. This reprogramming results in massive upregulation ...