title: Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function.
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.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Kuti
authors.initials: K
authors.lastname: Baruch
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Deczkowska
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: David
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Castellano
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Omer
authors.initials: O
authors.lastname: Miller
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kertser
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Tamara
authors.initials: T
authors.lastname: Berkutzki
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Barnett-Itzhaki
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Bezalel
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Wyss-Coray
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. michal.schwartz@weizmann.ac.il ido.amit@weizmann.ac.il.
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel. michal.schwartz@weizmann.ac.il ido.amit@weizmann.ac.il.
authors.forename: Michal
authors.initials: M
authors.lastname: Schwartz
mesh_terms: D000375:Aging / Q000235:genetics / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D002831:Choroid Plexus / Q000378:metabolism*; D003071:Cognition; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology; D050835:Interferon Regulatory Factors / Q000235:genetics*; D007370:Interferon Type I / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis; D017471:Receptors, Interferon / Q000235:genetics; D000096743:Interferon gamma Receptor
chemical_list: D050835:Interferon Regulatory Factors; D007370:Interferon Type I; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor