The aged hematopoietic system promotes hippocampal-dependent cognitive decline.
The aged hematopoietic system promotes hippocampal-dependent cognitive decline.
复制标题
衰老的造血系统促进海马依赖性认知能力下降。
DOI：
10.1111/acel.13192
复制
发表时间：
2020
期刊：
影响因子：
7.8
通讯作者：
Villeda,SaulA
中科院分区：
文献类型：
--
作者：
Smith,LucasK;Verovskaya,Evgenia;Bieri,Gregor;Horowitz,AlanaM;vonUngern-Sternberg,SaskiaNI;Lin,Karin;Seizer,Peter;Passegué,Emmanuelle;Villeda,SaulA
衰老的全身环境促进了海马体的细胞和认知损伤。在这里，我们报告了造血系统的老化直接有助于老年血液对认知的延缓衰老作用。利用异基因造血干细胞(HSC)移植模型(年轻小鼠的血液由老年HSC重建)，我们发现暴露在旧的造血系统中会抑制海马神经发生，减少突触标志物的表达，并损害认知。我们确定了由老年HSCs重组的年轻小鼠的血液中有许多升高的因子，其中亲环素A(CyPA)起到了促进衰老的作用。全身性CyPA水平的增加会损害年轻小鼠的认知能力，而抑制老年小鼠的CyPA水平会改善认知能力。总而言之，这些数据确定了与年龄相关的造血系统变化是海马体老化的驱动因素。
The aged systemic milieu promotes cellular and cognitive impairments in the hippocampus. Here, we report that aging of the hematopoietic system directly contributes to the pro‐aging effects of old blood on cognition. Using a heterochronic hematopoietic stem cell (HSC) transplantation model (in which the blood of young mice is reconstituted with old HSCs), we find that exposure to an old hematopoietic system inhibits hippocampal neurogenesis, decreases synaptic marker expression, and impairs cognition. We identify a number of factors elevated in the blood of young mice reconstituted with old HSCs, of which cyclophilin A (CyPA) acts as a pro‐aging factor. Increased systemic levels of CyPA impair cognition in young mice, while inhibition of CyPA in aged mice improves cognition. Together, these data identify age‐related changes in the hematopoietic system as drivers of hippocampal aging.