New work led by Stanford University scientists has revealed killer immune cells have been found to collect in parts of the brain where new nerve cells are generated. This damaging proliferation seems to naturally increase as a brain ages and the researchers hypothesize this may be a mechanism that underpins general age-related cognitive decline.
Neurogenic niches are spots in the brain holding neural stem cells and other cell types important for the generation of new neurons. An aging brain only retains a small volume of these neurogenic niches, and as we get older they become less functional.
The new research began by comprehensively cataloging the expression of genes in large cell samples taken from a neurogenic niche in the brains of two different age groups of mice. The research revealed a compelling difference between the two groups, with higher traces of immune cells known as killer T cells found in the brain samples from the old mice.
“We did find an extremely sparse population of killer T cells in the subventricular zone of young mice,” says Anne Brunet, senior author on the new study. “But in the older mice, their numbers were expanded by 16-fold.”
These specific killer T cells were found nestled in with neural stem cells, and more strikingly, were found to secrete an inflammation-promoting substance that put a halt to the new generation of nerve cells. The research also found evidence to suggest these killer T cells had not just accidentally crossed the blood-brain barrier, but showed signs of being drawn to the specific location by target antigens. So this process is not simply due to an age-related weakening of the blood-brain barrier, but instead it points to an as yet unknown process that may be fundamentally triggered by aging.
Corroborating these results in humans involved comprehensive examination of autopsied human brain tissue, which affirmed the presence of killer T cells in the brains of older humans.
“The textbooks say that immune cells can’t easily get into the healthy brain, and that’s largely true,” says Brunet. “But we’ve shown that not only do they get into otherwise healthy aging brains – including human brains – but they reach the very part of the brain where new neurons arise.”
The next step for the researchers is to try to uncover what particular antigens are drawing these killer T cells into the aging brain. If this process can be disrupted then it’s possible a certain volume of age-related cognitive decline could be prevented.