Inflammatory Signals and Neural Regeneration in Aging

In old age, the number of stem cells in the brains of mice decreases drastically. Those that remain protect themselves from completely vanishing by entering a state of dormancy, according to research published today in Cell.

Stem cells in certain areas of the adult brain are capable of generating new neurons for life. These stem cells are also activated in the wake of injury to the brain and, additionally, may form the cells of origin to specific brain tumors.

However, in the aging brain, the replenishment of young neurons diminishes. Scientists on the team of Ana Martin-Villalba of the German Cancer Research Center (DKFZ) in Heidelberg, have now discovered a cause for this loss of function. They discovered that the number of stem cells drastically declines as aging progresses.

“This is because most stem cells disappear in the process of differentiating into mature brain cells and only a small portion of them generates new stem cells,” Martin-Villalba explains. “If they did not increasingly enter into a state of dormancy without dividing actively as the brain ages, the supply of stem cells in the brain of an old mouse would be completely exhausted. They are using the dormancy to gain time.”

As the number of dormant stem cells increases in old age, they also become harder to awaken with emergency signals such as injury. But once awakened, they are just as potent as young stem cells in regenerating neurons.

The team found out that the dormancy appears to be promoted by inflammatory chemical messengers and signals of the key Wnt signaling chain that are transmitted from the stem cells’ immediate surroundings. When these signals are blocked using antibodies, the dividing activity of neural stem cells increases again and they provide more neurons for everyday life as well as for repair processes.

“The central finding of our work is that dormancy promoted by inflammation is a key characteristic of aging brain stem cells,” says Martin-Villalba. “However, drugs can be used to reduce inflammation. This may be an approach to stimulating the regeneration of neurons and initiating repair mechanisms in the brain in old age.”