A basic signaling pathway known to play important roles in normal cell and cancer cell formation also plays an unexpected role as a molecular switch that controls the aging process of hematopoietic stem cells (HSCs), according to research led by Cincinnati Children’s and the University of Ulm in Germany.

Eventually, the scientists hope their findings will lead to ways for the elderly to boost their immune systems, fight illnesses and enhance overall vitality.

“Although there is a large amount of data showing that blood stem cell function declines during aging, the molecular processes that cause this remain largely unknown. This prevents rational approaches to attenuate stem cell aging,” says Hartmut Geiger, PhD, senior investigator and a scientist at Cincinnati Children’s and the University of Ulm. “This study puts us significantly closer to that goal.”  

Properly functioning HSCs – which form in the bone marrow – produce the various types of blood cells necessary to a healthy immune system. HSCs also are important for regenerating other important cells in the body.

In mouse models, the team observed that as HSCs age, a normal pattern in the Wnt signaling pathway within HSCs  shifts into an atypical pattern that leads to cell death.

This shift appears to be triggered by sharply increased expression of the protein Wnt5a. In mice bred to be unable to express Wnt5a, the aging process of their HSCs was delayed compared to normal mice, the new study shows, while suppression of Wnt5a in aged HSCs rejuvenated them.

Detailed findings were published online Oct. 20, 2013, in Nature.

While the study advances our understanding of how aging works at the molecular level, much more research is needed to make these findings therapeutically relevant, Geiger says.  It remains unclear whether a drug can be developed to block Wnt5a in humans without causing other harm.

Article written by Nick Miller, Cincinnati Children’s. Contact: nicholas.miller@cchmc.org