Age-related memory decline could be caused by ageing immune cells.Credit: JasonDoiy/Getty
A type of immune cell circulating in the blood contributes to cognitive ageing, and blocking its effects can reverse the changes, suggests a mouse study published in Immunity on 14 May1.
T cells have many jobs, chiefly destroying pathogens. But as people age, a group of T cells called CD8+ cells begin to infiltrate the brain tissue, where they secrete an enzyme that causes inflammation and prevents brain cells from regenerating. Many more CD8+ cells remain in the bloodstream, but their role in ageing wasn’t known until now.
In the latest study, researchers show that this large population of ‘non-infiltrating’ T cells actively contributes to cognitive decline. Blocking these effects in the blood might be a more realistic treatment strategy than targeting the cells in the brain, say researchers.
“We don’t even have to get into the brain to start treating cognitive decline,” says study co-author Saul Villeda, a neuroscientist at the University of California, San Francisco. “We can actually block things in blood to have an impact on memory.”
The discovery that these cells influence the brain from the outside “reveals something entirely new”, says Paloma Navarro Negredo, a neuroimmunologist at the Swiss Federal Institute of Technology in Lausanne.
Old blood meets young
To understand the factors that influence cognitive ageing, Villeda’s team used a surgical technique called parabiosis to join the circulatory systems of two mice — one old, one young. The researchers wanted to see whether the young immune cells aged in the presence of older blood, and vice versa. They found no changes in how the cells behaved, which Villeda says suggested that the older non-infiltrating CD8+ cells were somehow driving the ageing process, rather than being influenced by other factors.
To study the role of aged non-infiltrating CD8+ cells in degeneration, the researchers injected a fresh group of young mice with old cells and another group with young cells to determine their effect on the brain’s hippocampus, which regulates memory and learning. The team sequenced RNA from the mice and found that genes associated with mental sharpness were expressed at lower levels in the mice that had been injected with aged cells.
The authors also put the mice through object-recognition challenges and a maze, to observe functional effects. The mice with young cells showed more interest in new objects than did those with older cells, and completed the maze quicker.
