Agrawal Neetu, Afzal Muhammad, Khan Nawaid Hussain, Ganesan Subbulakshmi, Kumari Mukesh, Sunitha S, Dash Aniruddh, Goyal Kavita, Kushwaha Brajgopal, Rekha A, Rana Mohit, Ali Haider
Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India.
Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, Jeddah, 21442, Saudi Arabia.
Biogerontology. 2025 Mar 22;26(2):77. doi: 10.1007/s10522-025-10219-w.
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.
血管内皮生长因子（VEGF）是血管性痴呆（VD）发病机制和治疗发展中的关键因素，同时仍受到衰老过程和细胞衰老机制的强烈影响。VEGF的多种作用包括神经保护功能、其在血管发育中的作用以及调节脑血流系统的能力，所有这些都有助于维持认知功能。前额叶皮质的VEGF基因水平升高，这与阿尔茨海默病和VD患者认知缺陷的进展直接相关。这些患者脑脊液中的VEGF水平较高，表明疾病病理包括多个不可分割的因素。衰老会显著恶化VEGF的调节，因为内皮功能障碍与慢性炎症和氧化应激相结合，会产生包括动脉粥样硬化和中风在内的不良血管症状。细胞衰老通过引发破坏性炎症反应以及损害血管修复能力，使这些过程变得更加复杂。衰老细胞（SCs）分泌的促炎细胞因子会破坏VEGF信号传导，对血管健康和认知健康都产生有害影响。VEGF-A165a和VEGF-A165b变体的神经保护特性表明它们能够减轻β-淀粉样蛋白和tau蛋白的毒性。VEGF的保护机制在很大程度上取决于VEGF的表达水平和受体功能，而这两者都会随着衰老而降低。调节VEGF信号传导和SCs积累的联合方法显示出设计针对VD治疗的潜力。通过食用地中海饮食、进行有氧运动以及开发包括衰老细胞溶解剂和衰老细胞形态调节剂在内的疗法来延缓神经退行性进展，人们可以在更长时间内维持血脑屏障功能。未来的研究工作必须改进VEGF的递送方法，同时研究细胞衰老机制并开发检测SCs细胞的先进方法。将VEGF靶向治疗与抗衰老干预措施和详细诊断技术相结合的三维医疗保健方法显示出有效管理VD以取得更好患者效果的潜力。
