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Rejuvenation of cerebromicrovascular function in aged mice through heterochronic parabiosis: insights into neurovascular coupling and the impact of young blood factors
Rafal Gulej # 1 2, Ádám Nyúl-Tóth # 1 2 3, Boglarka Csik 1 2 3, Benjamin Petersen 1 2, Janet Faakye 1 2, Sharon Negri 1 2, Siva Sai Chandragiri 1 2, Peter Mukli 1 2 3, Andriy Yabluchanskiy 1 2 3 4, Shannon Conley 2 5, Derek M Huffman 6 7, Anna Csiszar 1 2 4 8, Stefano Tarantini 1 2 3 4, Zoltan Ungvari 9 10 11 12
Abstract:
Age-related impairment of neurovascular coupling (NVC; "functional hyperemia") is a critical factor in the development of vascular cognitive impairment (VCI)...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...
