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.
Thursday, October 09, 2014
Inflammatory signaling is bad for the aging brain.
Baruch et al. do some interesting work suggesting that preventing antiviral-like responses may protect aging brain function. They find that the choroid plexus of older mice produces more RNA for the inflammatory cytokine interferon-I than younger mice. This increase is also seen in human post-mortem brain samples. (The choroid plexus produces cerebrospinal fluid that bathes the brain, is exposed both to blood and cerebrospial fluid, and constitutes the blood–cerebrospinal fluid barrier.) Blocking interferon signaling in the aging mouse brain partially restored cognitive function. Here is their abstract: