About the Article
Article Files
[This article belongs to Volume - 70, Issue - 6]
Published on : 2025-06-17 14:44:56
Article Code: AMJ-17-06-2025-12321
Title : Senolytic-Induced Clearance of Senescent Astrocytes Mitigates Neurovascular Unit Deterioration in Post-COVID-19 Cognitive Impairment
Author(s) : Dr. Elena Volkov, Dr. Thomas Müller
Abstract :
Post-acute sequelae of SARS-CoV-2 infection (PASC) frequently manifest as persistent cognitive deficits, yet
underlying neurobiological mechanisms remain elusive. We demonstrate that SARS-CoV-2 spike protein induces
cellular senescence in cortical astrocytes through p16INK4a/p21Cip1 pathway activation, triggering blood-brain
barrier breakdown and synaptic pruning. Administration of the senolytic combination dasatinib plus quercetin (D+Q)
in a hamster model of long COVID selectively eliminated senescent astrocytes, restored pericyte coverage, and
improved spatial memory performance. Transcriptomic analysis revealed dampened interferon-stimulated gene
expression and normalized vascular endothelial growth factor signaling. These findings position astrocytic
senescence as a targetable node in post-viral neurodegeneration.