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

Science  03 Oct 2014:
Vol. 346, Issue 6205, pp. 89-93
DOI: 10.1126/science.1252945

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Excess signaling is bad for the aging brain

Preventing antiviral-like responses may protect function in the aging brain. Baruch et al. monitored messenger RNA production in the choroid plexus, the interface between the blood and cerebrospinal fluid, in young and old mice (see the Perspective by Ransohoff). They detected an inflammatory response in older mice not present in the brain of young mice that was also seen in old aged human samples postmortem. Preventing signaling by the cytokine interferon-I, which normally helps in the antiviral response of the immune system, helped prevent the decrease in cognitive function seen in aged mice.

Science, this issue p. 89; see also p. 36

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.

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