Cellular Senescence in Vascular Dementia (VaD)

Cerebrovascular dysfunction that reduces cerebral perfusion and leads to progressive cognitive impairment as the cause of vascular dementia (VaD), the second most common type of dementia in the world. According to new research, the pathophysiology can be substantially affected by cellular senescence, an irreversible cell-cycle arrest resulting from stresses including oxidative damage, DNA instability, and mitochondrial failure. The SASP that senescent cells, predominantly represented within the endothelial, glial, and neuronal populations, develop is characterized by pro-inflammatory cytokines, matrix-degrading enzymes and reactive oxygen species, the latter of which exacerbates dysfunction of the neurovascular units. These all play a part in neuronal loss and cognitive decline through interruption of the blood–brain barrier integrity and the induction of sustained neuroinflammation and vascular reactivity compromise. Senescence markers (including p16ink4a, p21CIP1, and SA-β-gal) have been demonstrated to be upregulated in the brain of animals with VaD-like pathologies during preclinical models, as well as the cerebrovascular tissues of the VaD postmortem humans. More and more frequently, senescent cell targeting is being seen as a therapeutic option. Senolytics, or substances that specifically kill senescent cells, and senomorphics, or substances that modify the SASP without killing cells, show potential as a VaD course cessation or reversal treatment. Interventions that moderate inflammation and oxidative damage may also indirectly mitigate senescence-related disease. Cells senescence biology incorporation into VaD research might result in the measurement of new biomarkers and disease-modifying interventions in the aged population. This study relieves the promise of a senescence-targeted approach to transform the treatment landscape of vascular cognitive impairment by examining the molecular underpinnings correlating senescence with VaD.