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Science. 2014 Oct 3;346(6205):89-93. doi: 10.1126/science.1252945. Epub 2014 Aug 21.

Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function.

Author information

1
Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
2
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
3
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
4
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. michal.schwartz@weizmann.ac.il ido.amit@weizmann.ac.il.
5
Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel. michal.schwartz@weizmann.ac.il ido.amit@weizmann.ac.il.

Abstract

Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent gene expression profile that was also found in aged human brains. In aged mice, this response was induced by brain-derived signals, present in the cerebrospinal fluid. Blocking IFN-I signaling within the aged brain partially restored cognitive function and hippocampal neurogenesis and reestablished IFN-II-dependent choroid plexus activity, which is lost in aging. Our data identify a chronic aging-induced IFN-I signature, often associated with antiviral response, at the brain's choroid plexus and demonstrate its negative influence on brain function, thereby suggesting a target for ameliorating cognitive decline in aging.

PMID:
25147279
PMCID:
PMC4869326
DOI:
10.1126/science.1252945
[Indexed for MEDLINE]
Free PMC Article

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