Findings published today involving scientists at the Babraham Institute in Cambridge, shed new light on the effects of ageing on blood and the immune system. The study of haematopoietic stem cells – which produce new blood and immune cells – reveals that some stem cells age faster than others. The older stem cells slowly lose the ability to produce new cells, which could go some way to explain why older people experience weaker immune systems and a greater risk of conditions such as anaemia.
The research, collaboratively led Professor Wolf Reik at the Babraham Institute and Professor Tony Green at the Department of Haematology, University of Cambridge, used recently developed techniques to examine individual haematopoietic stem cells from mice. The findings, published in Cell Reports, show that the more new cells each stem cell produces the faster it ages and the sooner it gets exhausted.
Stem cells are any group of cells in the body that are able to divide to produce several different types of new cells, therefore their correct functioning is essential. Although embryonic stem cells are well known, there are also adult stem cells in different parts of the body. Each type of adult stem cell only has a limited repertoire of cells it can produce, and usually helps to maintain specific organs or systems in the body, such as the brain, blood or digestive system.
By encouraging haematopoietic stem cells to make more new cells, the team were able to accelerate the ageing process and make more ‘old’ cells, showing that ageing of haematopoietic stem cells is linked to the number of cells they have produced in their lifetime. This also suggests that some people may have healthier stem cells than others, whilst others may be more prone to illnesses resulting from aged cells.
What the team – which also includes scientists from the Department of Haematology, University of Cambridge and the MRC Human Genetics Unit in Edinburgh – has found is an example of heterogeneity, a marked difference between individuals within a group. In haematopoietic stem cells, the oldest cells enter a state called senescence, where they no longer produce new cells.
The paper’s co-first and co-corresponding author Dr Kristina Kirschner, now based at the University of Glasgow, said: “We’ve known for some time that haematopoietic stem cells slowly lose the ability to produce new cells as they age but until now we’ve assumed this is due to a general slowing down of the whole cell population. Finding that some cells become senescent long before others means we need to rethink our approach to cell ageing.”
The paper's other first author, Dr Tamir Chandra, goes on to say: "Much more needs to be done to understand why the cells age at different rates. For example, this could be part of a strategy adopted to maintain the right number of stem cells, or it might just be an accidental side effect of producing new cells.”
Although some of the cells from old mice were senescent, many more were indistinguishable from healthy cells in much younger mice. The researchers found that the older cells include high levels of activity in a biological system called JAK/STAT, which can be a key factor in certain blood cancers. As such, these aged stem cells may also help to explain the increased risk of certain leukaemias and lymphomas in older people.
As one of the senior authors on the paper, Professor Reik said, “Technology has now advanced to the point where we’re able to study the inner workings of single cells. Only through these approaches can we make sense of heterogeneity in biology and find better ways to treat disease and stay healthy as we age.”
By understanding how stem cells change throughout our lives, Professors Reik and Green hope to find ways to turn back the clock for haematopoietic stem cells. The eventual goal would be to stop the immune system from weakening with age and potentially take preventative action to remove aged cells from the body before they have an opportunity to become harmful or develop into cancer. Such interventions could help more people stay healthy for longer in their advancing years.
Professor Green summarised this by saying: "In the long term, we want people to benefit from more tailored approaches to manaing their health. Preventative measures could help to slow or even stop the onset of immune defects with age and reduce the risk of certain types of blood cancer."
Kirschner, K., Chandra, T. et al., Proliferation drives ageing related functional decline in a subpopulation of the
haematopoietic stem cell compartment., Cell Reports 19, 1503-1511, (2017). doi: http://dx.doi.org/10.1016/j.celrep.2017.04.074
Kristina Kirschner is supported by a Wellcome Trust ISSF Fellowship and Tamir Chandra is
supported by a Chancellor’s Fellowship held at the University of Edinburgh.
The Reik lab is funded by the BBSRC, the Wellcome Trust , EU BLUEPRINT, and EpiGeneSys. The Green lab is supported by Bloodwise, the Wellcome Trust, the Medical Research Council, the Kay Kendall Leukaemia Fund, the Cambridge NIHR Biomedical Research Center, the Cambridge Experimental Cancer Medicine Centre, the Leukemia and Lymphoma Society of America and a core grant through the Wellcome Trust‐Medical Research Council Cambridge Stem Cell Institute. The Hemberg lab is supported by a Wellcome Trust core grant to the Wellcome Trust Sanger Institute.
Dr Jonathan Lawson, Babraham Institute Communications Managerjonathan.firstname.lastname@example.org
Image source: Figure 1B of the publication - a graphical representation of relative gene activity in haematopoietic stem cells from old and young mice.
Affiliated Authors (in author order):
Tamir Chandra formerly Epigenetics Programme, Babraham InstituteWolf Reik, Group Leader, Epigenetics Programme, Babraham Institute
About the Babraham Institute:
The Babraham Institute receives strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC) to undertake world-class life sciences research. It's goal is to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Research focuses on signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing.
Animal research statement:
As a publically funded research institute and a signatory of the Concordat on Openness in Animal Research, the Babraham Institute is committed to engagement and transparency in all aspects of its research. The research presented here used mice kept within the University of Cambridge Central Biological Services Unit. Haematopoietic stem cells were collected from a strain of laboratory research mice known as C57 black 6 between 4 and 18 months old so they could be assessed for their RNA content, protein content and ability to behave as stem cells.
All animal work was carried out in accordance with the Animals (Scientific Procedures) Act 1986, under a UK Home Office project licence. Details of the animals used in these studies can be found in the methods section of the paper.
Please follow the link for further details of the Institute’s animal research and our animal welfare practices.
23 May 2017