The aged hematopoietic system promotes hippocampal-dependent cognitive decline
Lucas K Smith1,2, Evgenia Verovskaya3,4, Gregor Bieri1
1Department of Anatomy, University of California San Francisco, San Francisco, CA, USA.
Aging Cell
|October 19, 2020
Summary
Aging blood cells directly impair brain function and memory. This study shows that changes in the hematopoietic system accelerate cognitive decline and hippocampal aging, identifying cyclophilin A as a key factor.
Area of Science:
- Neuroscience
- Gerontology
- Hematology
Background:
- The aging process is associated with systemic changes that negatively impact cognitive function, particularly in the hippocampus.
- The contribution of the hematopoietic system to age-related cognitive decline is not fully understood.
Purpose of the Study:
- To investigate the direct role of the aging hematopoietic system in cognitive impairments.
- To identify specific blood-borne factors contributing to hippocampal aging.
Main Methods:
- Utilized a heterochronic hematopoietic stem cell (HSC) transplantation model in mice.
- Administered cyclophilin A (CyPA) to young mice and inhibited CyPA in aged mice.
Main Results:
- Exposure to an aged hematopoietic system in young mice led to inhibited hippocampal neurogenesis, reduced synaptic marker expression, and cognitive deficits.
- Elevated levels of cyclophilin A (CyPA) were identified in the blood of mice with aged HSCs.
- Increased systemic CyPA impaired cognition in young mice, while CyPA inhibition improved cognition in aged mice.
Conclusions:
- Age-related alterations in the hematopoietic system are direct drivers of hippocampal aging and cognitive impairment.
- Cyclophilin A (CyPA) is a key pro-aging factor in the blood that mediates cognitive decline.
- Targeting the hematopoietic system and factors like CyPA may offer therapeutic strategies for age-related cognitive dysfunction.
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