DNA ‘barcodes’ shed light on how the blood ages
The discovery could help prevent diseases years before symptoms appear, as well as paving the way for the exploration of rejuvenation therapies.
Scientists have discovered “barcodes” embedded in DNA that shed light on how the blood ages.
It is hoped the discovery could help prevent illnesses such as blood cancer or heart disease before symptoms appear.
It could also pave the way for the exploration of therapies that slow down or reverse ageing, researchers suggested.
The study, published in the journal Nature, identified stem cells that gradually take over blood production between the ages of 50 and 60.
These cells, known as “clones”, prefer to produce myeloid cells, a type of immune cell linked to chronic inflammation.
Young people have between 50,000 and 200,000 stem cells, which are responsible for replacing between 100 billion and 200 billion blood cells every day.
“As we age, some of these stem cells disappear and their function needs to be taken over by others, which then expand,” said Dr Lars Velten, group leader at the Centre for Genomic Regulation (CRG) in Barcelona.
“And by the age of 50 or 60, we get these clones. This is a group of cells that stem from the same mother stem cell.
“And these clones are important because they are first step in leukaemia formation, and they also contribute to inflammation, because the blood cells that derive from them are emitting molecules that fuel the inflammation process, and therefore there’s also this link to heart disease risk.”
According to Dr Velten, tracking every blood cell back to its original stem cell has been possible only in animal research.
His team looked at changes in the chemical tags, known as methylation marks, attached to DNA.
Theses tags help cells know which genes to switch on and off, and when a stem cell divides, methylation marks are copied to its daughter cells.
“This is sort of like having a unique barcode for every cell when we’re young, and then this barcode identifies all the descendants, all the children and grandchildren and great-grandchildren, of these cells as we age,” Dr Velten added.
To read these “barcodes”, scientists developed a technique known as EPI-Clone.
They used it to reconstruct the history of blood production in both mice and humans, tracing which stem cells contributed to making blood.
In older mice, EPI-Clone showed that blood stem cells comprised just a few dozen large clones.
The pattern was also found in humans, with larger clones taking over blood production from age 50.
This discovery could one day allow doctors to look at how a patient’s blood is ageing, potentially years before diseases develop, researchers suggested.
Dr Alejo Rodriguez-Fraticelli, also group leader at IRB Barcelona, said: “The idea is that this could be an early intervention tool for cancers, starting with blood cancers, where we know that expansions in these stem cells identify individuals that are at risk of developing blood malignancies.”
The study also found many of the dominant clones produced myeloid cells, which are linked to chronic inflammation.
Research using mice has shown removing these particular clones can rejuvenate blood stem cells.
Researchers are hopeful the tool could pave the way for the exploration of rejuvenation therapies in humans as it allows for scientists to pinpoint problematic clones.
Dr Rodriguez-Fraticelli added: “If we target the expanded clones, there may be the hope that we may ablate them and then let the diversity of the hematopoietic system, the blood regeneration system, really rejuvenate.”
Dr Velten said: “If we want to move beyond generic anti-ageing treatments and into real precision medicine for ageing, this is exactly the kind of tool we need.
“We can’t fix what we can’t see and for the first time, EPI-Clone can facilitate this for humans.”
