Inside our bones, a busy and vital process is happening every single second.
Deep in the bone marrow, the body is constantly making millions of new blood cells and immune cells that keep us alive and protect us from illness.
This system normally works in a delicate balance. Special stem cells create new blood cells, supportive helper cells guide and protect those stem cells, and immune signals make sure everything stays in harmony.
As we grow older, however, this balance becomes easier to disturb. Aging, long-term inflammation, and hidden genetic changes that build up over time can slowly disrupt the communication between these cells.
When this happens, certain mutated blood stem cells can begin to multiply more than they should.
This condition is known as clonal hematopoiesis of indeterminate potential, or CHIP. Even though people with CHIP usually feel completely healthy and show no obvious symptoms, the condition is quite common in older adults.
It appears in about one out of every five people over the age of 60 and in nearly one out of three people over the age of 80.
While CHIP might seem harmless because there are no clear symptoms, it can lead to serious health problems. People with this condition have a much higher risk of developing blood cancers. They are also more likely to develop heart disease and to die earlier than people without CHIP.
A related condition called myelodysplastic syndrome, or MDS, is also linked to these abnormal stem cells. In MDS, the bone marrow can no longer make healthy blood cells properly.
This can lead to fatigue, infections, and bleeding problems. Around 30 percent of people with MDS will eventually develop acute myeloid leukemia, a fast-growing and often deadly form of blood cancer.
For many years, scientists have mainly focused on mutations inside the blood stem cells themselves to explain how these diseases develop. But one important question remained unanswered. What role does the surrounding environment inside the bone marrow play in helping these harmful changes grow and spread?
To answer this, an international group of scientists carried out a detailed study of the bone marrow environment in both healthy people and in patients with MDS. The research was led by Judith Zaugg from EMBL and the University of Basel, together with Borhane Guezguez from the University Medical Center Mainz.
They worked with bone marrow samples collected in Germany as part of a large research project that studies blood health in older adults.
Using powerful modern technologies, the scientists looked closely at individual cells inside the bone marrow. They studied the genes, proteins, and exact locations of different cell types. This allowed them to create an extremely detailed map of what was happening inside the marrow before and during the development of disease.
What they found was surprising. Long before any clear signs of disease appeared, the normal supportive cells in the bone marrow began to change. The healthy cells that usually help blood stem cells survive and grow were slowly replaced by a new type of highly inflammatory support cell.
These altered cells produced large amounts of substances that trigger inflammation in the body. At the same time, they attracted special types of immune cells, especially certain T cells that respond strongly to inflammation. Together, these cells created a cycle that kept inflammation alive inside the bone marrow.
This ongoing inflammation damaged the normal process of making healthy blood cells. It also changed the structure of the marrow itself and created an environment that made it easier for mutated stem cells to grow and take over.
Interestingly, the researchers did not find clear evidence that the mutated blood cells directly caused this inflammation. Instead, the environment around them seemed to become sick on its own, and this unhealthy setting then supported the development of disease.
Another key finding was that in people with MDS, important signals that normally hold blood stem cells in the bone marrow no longer worked properly. This may help explain why the bone marrow starts to fail. Without the right signals, the normal system of blood production breaks down.
The study also connects to a broader idea known as “inflammaging.” This term describes the slow, chronic inflammation that increases as we get older and is linked to many age-related illnesses, including cancer, heart disease, and metabolic disorders.
The bone marrow, once thought to be just a factory for making blood, now appears to be both a victim and a driver of this aging-related inflammation.
In reviewing and analysing this research, it becomes clear that the bone marrow environment plays a central role in the earliest stages of blood disease. The findings shift attention away from only the mutated cells and toward the entire environment that supports them.
This is important because it opens the door to new treatment ideas. Instead of trying only to destroy abnormal cells, future therapies could aim to calm inflammation inside the bone marrow or restore its healthy structure.
These approaches might slow down or even prevent the progression from harmless-looking CHIP to dangerous conditions like MDS and leukemia.
The study is also a reminder that aging changes our bodies in complex ways that are not always visible. Even when people feel healthy, hidden processes may be taking place at a cellular level.
By understanding these silent changes, doctors may one day be able to identify risk much earlier and step in before serious disease develops. This research marks an important step in that direction and gives scientists new hope for preventing some of the most dangerous blood disorders that affect older adults.
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The study is published in Nature Communications.
