PDF(Pubmed)
Abstract：
Age-related impairment of neurovascular coupling (NVC; \"functional hyperemia\") is a critical factor in the development of vascular cognitive impairment (VCI). Recent geroscience research indicates that cell-autonomous mechanisms alone cannot explain all aspects of neurovascular aging. Circulating factors derived from other organs, including pro-geronic factors (increased with age and detrimental to vascular homeostasis) and anti-geronic factors (preventing cellular aging phenotypes and declining with age), are thought to orchestrate cellular aging processes. This study aimed to investigate the influence of age-related changes in circulating factors on neurovascular aging. Heterochronic parabiosis was utilized to assess how exposure to young or old systemic environments could modulate neurovascular aging. Results demonstrated a significant decline in NVC responses in aged mice subjected to isochronic parabiosis (20-month-old C57BL/6 mice [A-(A)]; 6 weeks of parabiosis) when compared to young isochronic parabionts (6-month-old, [Y-(Y)]). However, exposure to young blood from parabionts significantly improved NVC in aged heterochronic parabionts [A-(Y)]. Conversely, young mice exposed to old blood from aged parabionts exhibited impaired NVC responses [Y-(A)]. In conclusion, even a brief exposure to a youthful humoral environment can mitigate neurovascular aging phenotypes, rejuvenating NVC responses. Conversely, short-term exposure to an aged humoral milieu in young mice accelerates the acquisition of neurovascular aging traits. These findings highlight the plasticity of neurovascular aging and suggest the presence of circulating anti-geronic factors capable of rejuvenating the aging cerebral microcirculation. Further research is needed to explore whether young blood factors can extend their rejuvenating effects to address other age-related cerebromicrovascular pathologies, such as blood-brain barrier integrity.
摘要：
与年龄相关的神经血管耦合损伤（NVC；“功能性充血”）是血管性认知障碍（VCI）发展的关键因素。最近的老年科学研究表明，仅靠细胞自主机制并不能解释神经血管衰老的所有方面。来自其他器官的循环因子，包括亲老年病因子（随年龄增加，对血管稳态有害）和抗老年病因子（防止细胞衰老表型，随年龄下降），被认为是协调细胞衰老过程的。本研究旨在探讨年龄相关的循环因子变化对神经血管衰老的影响。异慢性共生被用来评估暴露于年轻或年老的全身环境如何调节神经血管衰老。结果表明，与年轻的等慢性寄生虫相比，接受等慢性共生的老年小鼠（20个月大的C57BL/6小鼠[A-（A）]；6周的共生）的NVC反应显着下降（6个月大，[Y-(Y)])。然而,从寄生虫暴露于年轻血液显着改善老年异时寄生虫的NVC[A-（Y）]。相反，暴露于来自老年寄生虫的老年血液的年轻小鼠表现出受损的NVC反应[Y-(A)]。总之,即使短暂暴露于年轻的体液环境也可以减轻神经血管衰老表型，振兴NVC的反应。相反，在年轻小鼠中短期暴露于老化的体液环境会加速神经血管衰老特征的获得。这些发现强调了神经血管衰老的可塑性，并表明存在能够使衰老的脑微循环恢复活力的循环抗衰老因子。需要进一步的研究来探索年轻的血液因素是否可以扩展其恢复活力的作用，以解决其他与年龄相关的脑微血管病变，如血脑屏障的完整性。
