In mammals, nerve cells (neurons) are newly produced every day even in adults (neurogenesis).It is known that the source cells, neural stem cells and neural progenitor cells, decrease with age, and the number of newly born neurons also decreases. Why do neural stem cells and progenitor cells decrease with aging? Until now it has not been revealed.

　In this study, we found that p38 is the causative gene of the decrease in self-proliferative ability of neural progenitor cells due to aging using mice. It is said that p38 acts on neural progenitor cells to activate cell self-proliferation, but its expression decreases with aging, which is a major cause of decreased neurogenesis ability.

　In addition, it was found that forcible expression of p38 around the lateral ventricle of aged mice activates neural progenitor cells and promotes progenitor cell self-proliferation and neurogenesis.

　In previous studies on nerve regeneration, a method of activating neural stem cells to induce neurogenesis has been used, but there is a problem that neural stem cells are depleted after repeated division.On the other hand, in this method of maintaining the expression of p38 and promoting neurogenesis, it is known that p38 acts only on progenitor cells and does not affect neural stem cells.

　In fact, no depletion of neural stem cells was observed in the brains of mice in which p38 was forcibly expressed in the subventricular zone of the lateral ventricle for 1 year, and it was confirmed that this method enables long-term nerve regeneration.

　This result is expected to be applied not only to the aspect of aging research but also to nerve regeneration in various diseases caused by nerve loss such as dementia and depression.

Paper information:[Stem Cell Reports]: Involvement of p38 in age-related decline in adult neurogenesis via modulation of Wnt signaling