Endothelial Colony-Forming Cells (ECFCs) in cerebrovascular aging: Focus on the pathogenesis of Vascular Cognitive Impairment and Dementia (VCID), and treatment prospects

Endothelial colony-forming cells (ECFCs), a unique endothelial progenitor subset, are essential for vascular integrity and repair, providing significant regenerative potential. Recent studies highlight their role in cerebrovascular aging, particularly in the pathogenesis of vascular cognitive impairment and dementia (VCID). Aging disrupts ECFC functionality through mechanisms such as oxidative stress, chronic inflammation, and cellular senescence, leading to compromised vascular repair and reduced neurovascular resilience. ECFCs influence key cerebrovascular processes, including neurovascular coupling (NVC), blood-brain barrier (BBB) integrity, and vascular regeneration, which are critical for cognitive health. Age-related decline in ECFC quantity and functionality contributes to vascular rarefaction, diminished cerebral blood flow (CBF), and BBB permeability—processes that collectively exacerbate cognitive decline. This review delves into the multifaceted role of ECFCs in cerebrovascular aging and underscores their potential as therapeutic targets in addressing age-related vascular dysfunctions, presenting new directions for mitigating the effects of aging on brain health.