Counteracting hematopoietic ageing by pharmacological inhibition of TGFbeta and IL-6 signaling

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Stem cells are a special type of cell with the ability to make many other types of cell. As we age, the stem cells in our bone marrow stop working properly. This means that they are no longer able to make red blood cells (the cells that transport oxygen around the body) or white blood cells (the cells that help our body fight infections), quite as efficiently. This leads to a variety of health complications, from a weak immune system that can no longer fight infections, to a reduction in cognitive and cardiovascular ability and muscle strength.The functioning of any cell in our bodies, including bone marrow stem cells, depends on how their DNA is controlled. All cells have the same DNA code in them, but read this code in different ways. The code is divided into portions of information, like words in a sentence, called genes. Each gene tells the cell to do a different task, or make a different important component.To understand why ageing has this effect, in a previous project we compared the genes are turned on and off in bone marrow stem cells obtained from young and old mice. We discovered that there are two sets of genes that seem to be more active in old bone marrow stem cells. To check that these genes were really important, we looked at the 'production' line of cell components that they code for. We found that if we tampered with these production lines, we were able to revert some of the age-related effects in the bone marrow cells.In this project, we want to understand better how we can adjust these production lines to really revert the effects of ageing in bone marrow stem cells. In particular, we want to understand how tampering with one of these production lines (known as TGFbeta signalling pathway) can lead to an increased production of white blood cells and better protection against infections. We are also interested in understanding how tampering with both production pathways can increase the production of red blood cells.Ultimately, we hope that by understanding better how these two production lines interfere with the normal work of bone marrow stem cells, we may be able to devise ways to reverse it, and hopefully help patients affected by these conditions.