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

Science. 2014 Oct 3;346(6205):89-93. doi: 10.1126/science.1252945. Epub 2014 Aug 21.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Aging / pathology*
  • Animals
  • Brain / physiology*
  • Choroid Plexus / metabolism*
  • Cognition*
  • Gene Expression Regulation*
  • Hippocampus / cytology
  • Interferon Regulatory Factors / genetics*
  • Interferon Type I / physiology*
  • Mice
  • Mice, Transgenic
  • Neurogenesis
  • Receptors, Interferon / genetics


  • Interferon Regulatory Factors
  • Interferon Type I
  • Receptors, Interferon
  • interferon gamma receptor