Some of Your Blood Cells Carry Mutations. How You Live May Decide What They Do.
Five years of work, and what we found out about lifestyle, ageing blood, and the arteries of the heart:
There is a fact about ageing that almost nobody is told: as we get older, the stem cells in our bone marrow accumulate mutations. Occasionally one of those mutations gives a single stem cell a competitive edge, and its descendants slowly take over a growing share of our blood. This is called clonal hematopoiesis, and it can be detected in a quarter of people over 70 and half of people over 80, while being uncommon in the young and healthy.
It is not leukemia. Most people who have it will never develop a blood cancer. But it is not harmless either: these altered blood cells drive inflammation, and inflammation drives atherosclerosis — the fatty plaques that narrow arteries and raise the risk of heart attack and stroke.
That left the question I spent my postdoctoral years on. If clonal hematopoiesis is written into your bone marrow, is anything about it modifiable? Or is it simply something that happens to you?
What we asked
Cardiologists tell patients to sleep well and exercise. We can say with confidence that it helps hearts. What we could not say was whether it does anything to mutant cells specifically — whether lifestyle reaches all the way down into the bone marrow and changes the behaviour of the very cells carrying the mutation.
So we looked in two directions at once. We analysed physical activity and blood genomic data from more than 90,000 people in the UK Biobank and the NIH All of Us programme, and in parallel we studied mice carrying the specific mutations that matter most in humans, tracking what happened to their blood cells and their arteries under different sleep and exercise conditions.
What we found
Three things, and the third is the one I keep coming back to.
- Lifestyle reaches the mutant cell. In the human data, moderate-to-vigorous physical activity was associated with a lower incidence of clonal hematopoiesis and fewer mutant cells in the blood. In mice, undisturbed sleep and exercise slowed the expansion of the mutant clone and reduced the plaque burden in their arteries.
- It acts on the mutant cells selectively. This surprised us most. Sleep and exercise did not simply calm the whole bone marrow down. They reprogrammed the mutant progenitor cells — pushing them towards less proliferative, metabolically healthier behaviour — while leaving their non-mutated neighbours largely alone. Mutant cells turned out to be uniquely sensitive to how the body lives.
- It depends on which mutation you carry. Across mutations in Jak2, Tet2, Trp53 and Dnmt3a, the responses diverged: sleep and exercise curtailed clone expansion in Jak2- and Tet2-driven clonal hematopoiesis, but not in the Trp53- or Dnmt3a-driven forms. Not everyone’s biology responds to the same advice.
Mutant cells are not beyond reach. But which lever works depends on which mutation is driving the clone.
Why this matters
For most of my career, cardiovascular prevention advice has been broadly the same for everybody: sleep, move, don’t smoke, take your statin. That advice remains good. What this work adds is the beginning of a way to make it specific.
If we can identify the people carrying genetic cardiovascular risk factors in their blood, we can tell them which steps will actually shift their particular risk — and, just as importantly, be honest with those for whom lifestyle alone will not be enough, so that they receive something else instead. That is what precision prevention should look like: not the same message delivered louder, but the right message delivered to the right person.
There is also something I find quietly hopeful in this. The mutations themselves are not going anywhere. But a mutation is not a destiny — it is a tendency, and tendencies can be argued with. Some of that argument, it turns out, happens while you sleep.
The Science Behind
This project was carried out in the McAlpine Laboratory at the Icahn School of Medicine at Mount Sinai between 2023 and 2025, supported by a Walter Benjamin Fellowship of the German Research Foundation (DFG), with collaborators in the United States, Germany, and Belgium.
Two things worth adding to that page if you have them: the aorta plaque immunofluorescence image from the press release (check the Mount Sinai credit line before reuse), and a simple schematic of the mutation-dependent divergence — that’s the finding hardest to grasp from text alone.
One last thought on the site as a whole: with two lay-audience research stories now, you effectively have a science communication section. Cross-linking them (“This project grew out of earlier work on sleep after heart attack →”) would make the arc of your research legible to a visitor who lands on either one.