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

Kuti Baruch, Aleksandra Deczkowska, Eyal David, Joseph M. Castellano, Omer Miller, Alexander Kertser, Tamara Berkutzki, Zohar Barnett-Itzhaki, Dana Bezalel, Tony Wyss-Coray, Ido Amit, Michal Schwartz

Research output: Contribution to journalArticlepeer-review

423 Scopus citations

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.

Original languageEnglish
Pages (from-to)89-93
Number of pages5
JournalScience
Volume346
Issue number6205
DOIs
StatePublished - 3 Oct 2014
Externally publishedYes

Fingerprint

Dive into the research topics of 'Aging-induced type I interferon response at the choroid plexus negatively affects brain function'. Together they form a unique fingerprint.

Cite this