Aging-induced type I interferon response at the choroid plexus negatively affects brain function
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 pr...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2014-10, Vol.346 (6205), p.89-93 |
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| creator | Baruch, Kuti Deczkowska, Aleksandra David, Eyal Castellano, Joseph M. Miller, Omer Kertser, Alexander Berkutzki, Tamara Barnett-Itzhaki, Zohar Bezalel, Dana Wyss-Coray, Tony Amit, Ido Schwartz, Michal |
| description | 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. |
| doi_str_mv | 10.1126/science.1252945 |
| format | Article |
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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.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1252945</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington: American Association for the Advancement of Science</publisher><subject>Aging ; Aging (Individuals) ; Blood ; Brain ; Cerebrospinal fluid ; choroid plexus ; cognition ; Cognitive ability ; Cytokines ; Human behavior ; humans ; immune system ; Immune systems ; inflammation ; Interferon ; interferons ; messenger RNA ; Mice ; Neurobiology ; Rodents</subject><ispartof>Science (American Association for the Advancement of Science), 2014-10, Vol.346 (6205), p.89-93</ispartof><rights>Copyright © 2014 American Association for the Advancement of Science</rights><rights>Copyright © 2014, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c530t-cc137b4b6ced0fb12797789e2422f9d08ecbdfa9c77df609ad9afbd26081e05e3</citedby><cites>FETCH-LOGICAL-c530t-cc137b4b6ced0fb12797789e2422f9d08ecbdfa9c77df609ad9afbd26081e05e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/24917748$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/24917748$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2871,2872,27901,27902,57992,58225</link.rule.ids></links><search><creatorcontrib>Baruch, Kuti</creatorcontrib><creatorcontrib>Deczkowska, Aleksandra</creatorcontrib><creatorcontrib>David, Eyal</creatorcontrib><creatorcontrib>Castellano, Joseph M.</creatorcontrib><creatorcontrib>Miller, Omer</creatorcontrib><creatorcontrib>Kertser, Alexander</creatorcontrib><creatorcontrib>Berkutzki, Tamara</creatorcontrib><creatorcontrib>Barnett-Itzhaki, Zohar</creatorcontrib><creatorcontrib>Bezalel, Dana</creatorcontrib><creatorcontrib>Wyss-Coray, Tony</creatorcontrib><creatorcontrib>Amit, Ido</creatorcontrib><creatorcontrib>Schwartz, Michal</creatorcontrib><title>Aging-induced type I interferon response at the choroid plexus negatively affects brain function</title><title>Science (American Association for the Advancement of Science)</title><description>Aging-associated cognitive decline is affected by factors produced inside and outside the brain. 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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.</description><subject>Aging</subject><subject>Aging (Individuals)</subject><subject>Blood</subject><subject>Brain</subject><subject>Cerebrospinal fluid</subject><subject>choroid plexus</subject><subject>cognition</subject><subject>Cognitive ability</subject><subject>Cytokines</subject><subject>Human behavior</subject><subject>humans</subject><subject>immune system</subject><subject>Immune systems</subject><subject>inflammation</subject><subject>Interferon</subject><subject>interferons</subject><subject>messenger 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Science)</jtitle><date>2014-10-03</date><risdate>2014</risdate><volume>346</volume><issue>6205</issue><spage>89</spage><epage>93</epage><pages>89-93</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><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.</abstract><cop>Washington</cop><pub>American Association for the Advancement of Science</pub><doi>10.1126/science.1252945</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Science (American Association for the Advancement of Science), 2014-10, Vol.346 (6205), p.89-93 |
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| source | American Association for the Advancement of Science; Jstor Complete Legacy |
| subjects | Aging Aging (Individuals) Blood Brain Cerebrospinal fluid choroid plexus cognition Cognitive ability Cytokines Human behavior humans immune system Immune systems inflammation Interferon interferons messenger RNA Mice Neurobiology Rodents |
| title | Aging-induced type I interferon response at the choroid plexus negatively affects brain function |
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