When haematopoietic stem cells (HSCs) age, there is a switch from the so-called canonical Wnt signal transduction pathway to a non-canonical Wnt signal transduction process. The name Wnt derives from several previous molecular biological studies on the fruit fly Drosophila melanogaster and on mice. Signal transduction processes consist of a chain of biochemical events following a stimulus to the exterior of a cell. By means of various biochemical signalling cascades involving enzymes or hormones, the stimulus is transmitted to inside the cell; i.e. to the nucleus, with subsequent reading of a gene and production of a required protein. Via the Wnt signalling pathway, cells can respond to external stimuli with gene expression or metabolic regulation.

In contrast to the usual Wnt signalling pathway, other kinases are involved here: protein kinase C (a calmodulin-dependent protein kinase II), JNK and calcineurin. Protein kinases are enzymes that catalyze the transfer of a phosphate group to an amino acid.

In the course of the ageing process, more and more glycoproteins called Wnt5a appear, with a decisive influence on the ageing process of the stem cells. When a Wnt5a protein is blocked in old stem cells they stop ageing and rejuvenate; when the protein is blocked in young haematopoietic stem cells, they stop ageing.

The researchers believe that it is possible to interrupt the ageing process by inhibiting the Wnt5a protein with pharmaceutical drugs. They have been working on influencing the protein for some time, as the Wnt signal transduction process also plays a part in the development of metastases. WntA5 antibodies are commercially available.

More information:
Maria Carolina Florian, Kalpana J. Nattamai, Karin Dörr, Gina Marka, Bettina Überle, Virag Vas, Christina Eckl, Immanuel Andrä, Matthias Schiemann, Robert A. J. Oostendorp, Karin Scharffetter-Kochanek, Hans Armin Kestler, Yi Zheng & Hartmut Geiger (2013): A canonical to non-canonical Wnt signalling switch in haematopoietic stem-cell ageing. Nature 503: doi:10.1038/nature12631.

Source:
http://www.uniprot.org/uniprot/P41221
http://www.genecards.org/cgi-bin/carddisp.pl?gene=WNT5A
http://www.biotechnologie.de/BIO/Navigation/DE/root , did = 167818.html
http://www.signaling-gateway.org/molecule/query?afcsid=A002385