Gulej Rafal, Patai Roland, Ungvari Anna, Kallai Attila, Tarantini Stefano, Yabluchanskiy Andriy, Huffman Derek M, Conboy Michael J, Conboy Irina M, Kivimäki Mika, Csiszar Anna, Ungvari Zoltan
Vascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Oklahoma Center for GeroScience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Geroscience. 2025 May 23. doi: 10.1007/s11357-025-01657-y.
Aging is a complex biological process that detrimentally affects the brain and cerebrovascular system, contributing to the pathogenesis of age-related diseases like vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). While cell-autonomous mechanisms that occur within cells, independent of external signals from neighboring cells or systemic factors, account for some aspects of aging, they cannot explain the entire aging process. Non-autonomous, paracrine and endocrine, pathways also play a crucial role in orchestrating brain and vascular aging. The systemic milieu modulates aging through pro-geronic and anti-geronic circulating factors that mediate age-related decline or confer rejuvenative effects. This review explores the impact of systemic factors on cerebrovascular and brain aging, with a particular focus on findings from heterochronic parabiosis, blood exchange, and plasma transfer experiments. We discuss how these factors influence fundamental cellular and molecular processes of aging and impact cerebrovascular endothelial function, neurovascular coupling mechanisms, blood-brain barrier integrity, neuroinflammation, capillary density, and amyloid pathologies, with significant consequences for cognitive function. Additionally, we address the translational potential and challenges of modifying the systemic milieu to promote brain health and prevent age-related cognitive impairment.
衰老 是一个复杂的生物学过程，会对大脑和脑血管系统产生不利影响，促使诸如血管性认知障碍和痴呆（VCID）以及阿尔茨海默病（AD）等与年龄相关疾病的发病。虽然细胞内发生的、独立于来自相邻细胞的外部信号或全身因素的细胞自主机制解释了衰老的某些方面，但它们无法解释整个衰老过程。非自主的旁分泌和内分泌途径在协调大脑和血管衰老方面也起着关键作用。全身环境通过促衰老和抗衰老循环因子调节衰老，这些因子介导与年龄相关的衰退或产生恢复活力的作用。本综述探讨了全身因素对脑血管和大脑衰老的影响，特别关注异时联体共生、血液交换和血浆转移实验的结果。我们讨论了这些因素如何影响衰老的基本细胞和分子过程，以及如何影响脑血管内皮功能、神经血管耦合机制、血脑屏障完整性、神经炎症、毛细血管密度和淀粉样病变，对认知功能产生重大影响。此外，我们还讨论了改变全身环境以促进大脑健康和预防与年龄相关的认知障碍的转化潜力和挑战。
