Blood stem cells age at the unexpected flip of a molecular switch

PUBLIC RELEASE DATE:

20-Oct-2013

Contact: Jim Feuer jim.feuer@cchmc.org 513-636-4656 Cincinnati Children's Hospital Medical Center

Scientists report in Nature they have found a novel and unexpected molecular switch that could become a key to slowing some of the ravages of getting older as it prompts blood stem cells to age.

The study is expected to help in the search for therapeutic strategies to slow or reverse the aging process, and possibly rejuvenate these critically important stem cells (called hematopoietic stem cells, or HSCs), said scientists from Cincinnati Children's Hospital Medical Center and the University of Ulm in Germany who conducted study.

Published online Oct. 20, the study builds on earlier research from the same scientific team, who in 2012 reported they could make aging HSCs from laboratory mice functionally younger.

Properly functioning HSCs which form in the bone marrow are vital to the ongoing production of different types of blood cells that allow the immune system to fight infections. The cells are also important for the regeneration of other important cells in the body.

"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," said 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 through novel findings that show a distinct switch in a molecular pathway is very critical to the aging process."

The pathway is called the Wnt signaling pathway, a very important part of basic cell biology that regulates communications and interactions between cells in animals and people. Disruptions in the pathway have been linked to problems in tissue generation, development and a variety of diseases.

Analyzing mouse models and HSCs in laboratory cultures, the scientists observed in aging cells that a normal pattern of Wnt signaling (referred to in science as canonical) switched over to an atypical mode of activity (called non-canonical). They also noticed that the shift from canonical to non-canonical signaling was triggered by a dramatic increase in the expression of a protein in aged HSCs called Wnt5a.

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Blood stem cells age at the unexpected flip of a molecular switch