학술논문

Aging-induced type I interferon response at the choroid plexus negatively affects brain function.
Document Type
Article
Source
Science. 10/3/2014, Vol. 346 Issue 6205, p89-93. 5p.
Subject
*AGING
*MOLECULAR biology
*TYPE I interferons
*CHOROID plexus
*BRAIN physiology
*ANIMAL models for aging
*GENETIC regulation
*CEREBROSPINAL fluid
AGE factors in cognition disorders
Language
ISSN
0036-8075
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 FROM AUTHOR]