Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

21.10.2013
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.

When the researchers decided to test this observation by intentionally increasing the expression of Wnt5 in young HSCs, the cells began to exhibit aging characteristics.

Interestingly, the dramatic increase of Wnt5a in aged HSCs activated another protein called Cdc42, which turned out to be critical to stem cell aging. Cdc42 is the same protein the scientists targeted in their 2012 study. In that study, the authors showed that pharmacologically inhibiting Cdc42 reversed the aging process and rejuvenated HSCs to be functionally younger.

The researchers decided that for the current study, they would conduct experiments to see how blocking Wnt5a would affect HSC aging. To do so, they deleted Wnt5a from the HSCs of mice. They also bred mice to lack two functioning copies of the Wnt5a gene, which in essence blocked the protein's function in the HSCs of those animals. Deleting Wnt5 from cells functionally rejuvenated the HSCs. In mice bred to lack two functioning copies of the Wnt5a gene, the animals exhibited a delayed aging process in blood forming stem cells.

Although the study significantly expands what is known about the molecular causes of HSC aging, the authors emphasized more research is needed before knowing how the findings might become therapeutically relevant to people.

For one, researchers need to determine if increased Wnt5a expression is triggered from inside or outside of blood stem cells. Additionally, finding or developing a pharmacologic agent capable of blocking Wnt5a may be difficult because of how the protein functions.

Still, by tracking the causes of HSC aging back to an unexpected molecular switch in a fundamentally important pathway such as Wnt pathway, Geiger said researchers have pushed science much closer to understanding a critical part of getting older. Eventually, the scientists hope their work will lead to strategies for helping the elderly boost their immune systems, fight illnesses and enhance overall vitality.

Among the collaborators on the study was first author, Maria Carolina Florian, PhD, University of Ulm (Department of Dermatology and Allergic Diseases). Geiger is with the Division of Experimental Hematology/Cancer Biology at Cincinnati Children's and the Department of Dermatology and Allergic Diseases at the University of Ulm. Also collaborating were: Karin Dorr, Gina Marka, Bettina Ueberle, Virag Vas, Karin Scharffetter-Kochanek, Hans Armin Kestler (University of Ulm); Christina Eckl, Immanuel Andrä, Matthias Schiemann, Robert A. Oostendorp (Technische Universität Munchen, Germany); Yi Zheng, Kalpana J. Nattamai (Cincinnati Children's).

Work in the Geiger laboratory is supported by the Deutsche Forschungsgemeinschaft (KFO 142, GE2063/1, SFB1074), the German Federal Ministry of Education and Research, the Baden-Württemberg Foundation, National Institute of Health, (HL076604, DK077762, AG040118), the Edward P. Evans Foundation, the European Commission (FP7 Marie Curie Initial Training Network) and the Bausteinprogramm of the Department of Medicine, University of Ulm.

About Cincinnati Children's

Cincinnati Children's Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S. News and World Report's 2013 Best Children's Hospitals ranking. It is ranked #1 for cancer and in the top 10 for nine of 10 pediatric specialties. Cincinnati Children's, a non-profit organization, is one of the top three recipients of pediatric research grants from the National Institutes of Health, and a research and teaching affiliate of the University of Cincinnati College of Medicine. The medical center is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. Additional information can be found at http://www.cincinnatichildrens.org. Connect on the Cincinnati Children's blog, via Facebook and on Twitter.

Jim Feuer | EurekAlert!
Further information:
http://www.cchmc.org

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>