Scientists from the Centre for Chromosome Biology have been involved in a significant new international study that explains how blood production declines with age. Published in this week’s Nature magazine (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13619.html), the research may provide ways of mitigating the effects of ageing on the blood which can lead to diseases such as anaemia, immunoscenescence, bone marrow failure and myeloid malignancies. The study was led by the University of California, San Francisco in conjunction with the CCB and other researchers from the Spanish National Cancer Research Centre, Madrid, the University of Chicago and the University of California, Santa Cruz.
Our blood system can renew itself during our life. However, the key stem cells that are responsible for this become less effective as we age. This can give rise to blood diseases in older people, so the scientists sought to understand how these cells age. The study shows that critical components of blood stem cells’ replication machinery are lost during ageing, giving rise to replication stress, which is associated with cell cycle defects and chromosome gaps/breaks. This leads to particular biochemical marks being made on the genetic material that alter how genes work in aged blood stem cells and indicate the transcriptional silencing of ribosomal genes. It may be possible to manipulate these genetic marks for therapeutic or rejuvenation purposes.
The research was led by was led by PhD student Johanna Flach and Professor Emmanuelle Passegué from the University of California. The collaborators from NUI Galway were Dr Pauline Conroy and Professor Ciaran Morrison, of the Centre for Chromosome Biology. Commenting on the work, Professor Morrison said, ‘Many changes happen in cells at the molecular level during ageing- key genes are affected and even the integrity of the genome itself may be altered. How these changes affect cell functions is complicated. We need to understand the mechanisms behind each biochemical activity to get an overall picture of how stem cells work and of how they age. This study indicates an important pathway toward ageing in haematopoietic stem cells- understanding this may ultimately let us mitigate the effects of ageing on the blood.’
This work was funded by the California Institute for Regenerative Medicine and the US National Institutes of Health, with the NUI Galway work being supported by Science Foundation Ireland.