Inhibiting IFN-1 to Partially Restore Lost Cognitive Function
Researchers are expanding their exploration of signal molecules in the blood that differ in abundance between old and young individuals. Changing the levels in an old individual can somewhat restore stem cell function and partly turn back some other measurable declines that occur with aging, possibly through enhanced stem cell activities, possibly through other mechanisms. In considering aging as an accumulation of damage, these environmental changes are a reaction to that damage, a part of the evolved loss of stem cell activity with age that likely exists because it suppresses the risk of increasingly damaged cells spawning a cancer. The present human life span is a balance between diminished tissue maintenance on the one hand and cancer on the other. So it remains to be seen as to how to manage potential risks if this and other similar research is to produce useful treatments in the near term, though the benefits demonstrated in recent studies are large enough to make it well worth the effort:
Brain function declines in aging mammals. Recent work has identified dysregulation of key blood-borne factors whose altered expression during aging diminishes brain function in mice. Increased chemokine CCL11 expression with aging is detrimental to brain function. On the other hand, plasma levels of trophic factor GDF11 decrease with aging. Restoration of youthful levels of GDF11 by injection partially restores brain function and neurogenesis by improving endothelial cell function and vasculature. Moreover, GDF11 has a rejuvenative effect on cardiac and skeletal muscle.Decreased IFN-II and increased IFN-I signaling during aging at the choroid plexus (CP), which constitutes the brain-cerebrospinal fluid barrier (B-CPF-B), negatively effects brain function. Blood from young mice contains factors that restore IFN-II levels. IFN-II is required for maintenance of the CP and low IFN-II levels are associated with decreased cognitive abilities.
IFN-1 levels appear to drive increased CCL11 expression through the cerebrospinal fluid (CSF). Blood from young animals does not restore IFN-1 levels. However, injecting anti-IFNAR antibodies into the CSF inhibits downstream IFN-I gene and protein expression, and decreases expression of CCL11, partially restoring neurogenesis and cognitive function. These results suggest that IFN-1 plays a critical role to increase CCL11 during aging of brain. An emerging theme is that aging-associated loss of function in mammals may involve a set of defined, potentially reversible changes in many tissues and organs, including the brain, permitting development of potential rejuvenative therapies.