Age-related cerebromicrovascular changes, including blood-brain barrier (BBB) disruption and microvascular rarefaction, play a significant role in the development of vascular cognitive impairment (VCI) and neurodegenerative diseases. Utilizing the unique model of heterochronic parabiosis, which involves surgically joining young and old animals, we investigated the influence of systemic factors on these vascular changes. Our study employed heterochronic parabiosis to explore the effects of young and aged systemic environments on cerebromicrovascular aging in mice. We evaluated microvascular density and BBB integrity in parabiotic pairs equipped with chronic cranial windows, using intravital two-photon imaging techniques. Our results indicate that short-term exposure to young systemic factors leads to both functional and structural rejuvenation of cerebral microcirculation. Notably, we observed a marked decrease in capillary density and an increase in BBB permeability to fluorescent tracers in the cortices of aged mice undergoing isochronic parabiosis (20-month-old C57BL/6 mice [A-(A)]; 6 weeks of parabiosis), compared to young isochronic parabionts (6-month-old, [Y-(Y)]). However, aged heterochronic parabionts (A-(Y)) exposed to young blood exhibited a significant increase in cortical capillary density and restoration of BBB integrity. In contrast, young mice exposed to old blood from aged parabionts (Y-(A)) rapidly developed cerebromicrovascular aging traits, evidenced by reduced capillary density and increased BBB permeability. These findings underscore the profound impact of systemic factors in regulating cerebromicrovascular aging. The rejuvenation observed in the endothelium, following exposure to young blood, suggests the existence of anti-geronic elements that counteract microvascular aging. Conversely, pro-geronic factors in aged blood appear to accelerate cerebromicrovascular aging. Further research is needed to assess whether the rejuvenating effects of young blood factors could extend to other age-related cerebromicrovascular pathologies, such as microvascular amyloid deposition and increased microvascular fragility.

与年龄相关的脑微血管变化，包括血脑屏障（BBB）破坏和微血管稀疏，在血管性认知障碍（VCI）和神经退行性疾病的发展中发挥重要作用。利用异时性联体共生的独特模型，包括通过手术连接年轻和年老动物，我们研究了全身因素对这些血管变化的影响。我们的研究采用异时联体共生来探讨年轻和老年全身环境对小鼠脑微血管衰老的影响。我们使用活体双光子成像技术评估了配备慢性颅窗的联体生物对的微血管密度和血脑屏障完整性。我们的结果表明，短期暴露于年轻的全身因素会导致大脑微循环的功能和结构恢复活力。值得注意的是，我们观察到经历等时联体共生的老年小鼠（20 个月大的 C57BL/6 小鼠 [A-(A)]；联体共生 6 周）皮质中毛细血管密度显着降低，BBB 对荧光示踪剂的通透性增加），与年轻的等时性副生物（6 个月大，[Y-(Y)]）相比。然而，暴露于年轻血液的老化异时性副生物体（A-（Y））表现出皮质毛细血管密度显着增加和血脑屏障完整性恢复。相比之下，暴露于老年联生物（Y-(A)）的旧血液的年轻小鼠迅速出现脑微血管老化特征，毛细血管密度降低和血脑屏障通透性增加证明了这一点。这些发现强调了全身因素对调节脑微血管衰老的深远影响。暴露于年轻血液后，在内皮细胞中观察到的恢复活力表明存在对抗微血管衰老的抗老年元素。相反，老化血液中的促衰老因子似乎会加速脑微血管老化。需要进一步的研究来评估年轻血液因子的恢复活力是否可以扩展到其他与年龄相关的脑微血管病变，例如微血管淀粉样蛋白沉积和微血管脆性增加。