A research group at the University of Valencia, Spain, led by Isabel Fariñas Gómez, at the Molecular Neurobiology Unit, has discovered a mechanism that maintains stem cell populations in the brain and prevents these stem cells from overproliferating early in life and burning out.
Gómez’s group has discovered that the product of the CDKn1a/p21 gene is essential for maintaining brain stem cells. By keeping these stem cells active and functional, the brain dynamically changes as it learns and remembers, and maintains its good state of health. In the absence of p21, brain stem cell populations deplete and this prevents the formation of new neurons toward the end of life.
Stem cells require p21 to replicate themselves in a controlled fashion. In other cell types, p21 acts as a “tumor suppressor” gene. Tumor suppressor genes encode proteins that tend to put the brakes on cell proliferation. Loss-of-function mutations in tumor suppressor genes causes uncontrolled group and predisposes that cell and its descendants to become cancer cells.
However, in neural stem cells, p21 functions differently. Depletion of p21 from neural stem cells causes their depletion rather than their overgrowth. In short, an absence of p21 causes these cells to age.
This research, conducted in collaboration with Anxo Vidal from the University of Santiago de Compostela, shows that p21 in neural stem cells restrains the production of molecules that induce the depletion of these this stem cell population. Thus p21 restricts aging. According to Fariñas Gómez, “The research allows us to understand better how stem cells get lost in our brains as we age, and opens the possibility to try to alleviate this deterioration.”