The role of VEGF in vascular dementia: impact of aging and cellular senescence

Abstract

Vascular Endothelial Growth Factor (VEGF) is a critical element in vascular dementia (VD) pathogenesis and therapeutic development while remaining strongly influenced by aging processes and cellular aging mechanisms. VEGF's multiple effects comprise neuroprotective functions, its role in vascular development, and its ability to regulate brain blood flow systems, all leading to cognitive preservation. The prefrontal cortex exhibits elevated VEGF gene levels, which directly matches the advancement of cognitive deficits in patients with Alzheimer's disease and VD. These patients exhibit higher VEGF levels in their CSF fluid, demonstrating that disease pathology includes multiple inseparable factors. Aging dramatically worsens VEGF regulation because endothelial dysfunction combines with chronic inflammation and oxidative stress to generate adverse vascular symptoms that include atherosclerosis and stroke. Cellular senescence convolutes these processes by causing damaging inflammatory reactions alongside impaired vascular healing abilities. The secretion of pro-inflammatory cytokines from senescent cells (SCs) disrupts VEGF signaling and produces harmful consequences for both vascular health and cognitive well-being. The neuroprotective properties of VEGF-A165a and VEGF-A165b variants demonstrate their ability to lessen β-amyloid and tau protein toxicity. The protective mechanisms of VEGF depend heavily on VEGF expression levels and receptor functionality, both of which decrease with aging. The combination of approaches that modulate VEGF signaling and SC accumulation shows potential for designing treatments against VD. People can sustain BBB functionality over a longer period through Mediterranean diet consumption together with aerobic exercise along with developing therapies, including senolytics and senomorphics, which delay neurodegenerative progression. Future investigative efforts must improve VEGF delivery methods while studying cellular senescence mechanisms and developing advanced methods to detect SC cells. A three-dimensional healthcare approach combining VEGF-targeted treatments with anti-ageing interventions and detailed diagnostic techniques shows the potential for effective VD management to achieve better patient results.

Keywords: Aging; Angiogenesis; Cognitive impairment; Neuroprotection; Senolytics.