The aged hematopoietic system promotes hippocampal-dependent cognitive decline

被引：25

作者：

Smith, Lucas K. ^{[1
,2
]}

Verovskaya, Evgenia ^{[3
,4
]}

Bieri, Gregor ^{[1
]}

Horowitz, Alana M. ^{[1
,2
]}

von Ungern-Sternberg, Saskia N. I. ^{[5
]}

Lin, Karin ^{[1
,6
]}

Seizer, Peter ^{[5
]}

Passegue, Emmanuelle ^{[4
]}

Villeda, Saul A. ^{[1
,2
,6
]}

机构：

[1] Univ Calif San Francisco, Dept Anat, 513 Parnassus Ave,Box 0452, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Biomed Sci Grad Program, San Francisco, CA 94143 USA

[3] Eli & Edyth Broad Ctr Regenerat Med & Stem Cell R, San Francisco, CA USA

[4] Columbia Univ, Dept Genet & Dev, Irving Med Ctr, Columbia Stem Cell Initiat, New York, NY 10027 USA

[5] Univ Tubingen, Dept Cardiol & Cardiovasc Med, Tubingen, Germany

[6] Univ Calif San Francisco, Neurosci Grad Program, San Francisco, CA 94143 USA

来源：

AGING CELL | 2020年 / 19卷 / 08期

关键词：

aging; cognition; cyclophilin A; hematopoietic system; hippocampus; EXTRACELLULAR CYCLOPHILIN; YOUNG;

D O I：

10.1111/acel.13192

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：11

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