Mechanism that Prevents Stem Cell Aging

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.

p21 function

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.”

Stomach Cells Naturally Revert to Stem Cells

George Washington University scientists from St. Louis, Missouri have found that the stomach naturally produces more stem cells than previously realized. These stem cells probably repair stomach damage from infections, the foods we eat, and the constant tissue insults from stomach acid.

The reversion of adult cells to a stem cell fate is one of the goals of stem cell research. Shinya Yamanaka’s research group at the Center for iPS Cell Research and Application and the Institute for Frontier Medical Sciences at Kyoto University won the Nobel Prize in 2012 for his work on reprogramming adult cells into embryonic-like stem cells, otherwise known as induced pluripotent stem cells (iPSCs) that was initially published in 2006.

A collaborative research effort between scientists from Washington University School of Medicine in St. Louis and Utrecht Medical Center in the Netherlands have shown that this reversion from adult cells to stem cells occurs naturally in the stomach on a regular basis.

Jason Mills, associate professor of medicine at Washington University, said, “We already knew that these cells, which are called chief cells, can change back into stem cells to make temporary repairs in significant stomach injuries in significant stomach injuries, such as a cut to damage from infection. The fact that they’re making this transition more often, even in the absence of noticeable injuries, suggests that it may be easier than we realized to make some types of mature, specialized adult cells revert to stem cells.”

Chief cells normally produce a protein called pepsinogen. In the presence of stomach acid, pepsinogen activates itself and once active, the new protein product, pepsin, degrades proteins. Pepsin in an enzyme that is most active in the acidic environment of the stomach. Another enzyme released by chief cells is chymosin, which is also known as rennet. Chymosin curdles the proteins in milk and makes them easier to degrade.


Mills and his groups are in the process of studying the transformation of chief cells into stem cells, for injury repair. Mills would also like to investigate the possibility that the potential for growth unleashed by this change may contribute to stomach cancers.

Mills and his collaborator Hans Clevers from the Netherlands have identified stomach stem cell marker proteins that show that chief cells become stem cells even in the absence of serious injury. In the case of serious injury, either in cell culture of in animal models, more chief cells become stem cells, making it possible to repair the damage in the stomach.