RT’s Three Key Takeaways:

  1. Lifestyle Mitigation: Sufficient sleep and regular exercise can selectively repress the proliferation and expansion of mutant white blood cells associated with cardiovascular disease.
  2. Age-Related Risk: Clonal hematopoiesis (CH) affects approximately half of individuals over age 80 and increases the risk of harmful plaque formation in the arteries.
  3. Targeted Signaling: Physical activity and healthy sleep patterns can “turn off” inflammatory pathways in specific genetic mutations, such as Jak2 and Tet2, to reduce arterial lesion size.


Mount Sinai researchers found that healthy sleep and regular exercise can counteract genetic mutations in white blood cells associated with cardiovascular disease, according to a study published in Nature.

The study reported that sufficient sleep and exercise can help reduce the expansion of cells and atherosclerotic risk linked to mutations that spontaneously occur in white blood cells. These mutations, which accumulate over a lifetime, occur most often in hematopoietic stem cells in the bone marrow. These cells produce blood cells, including macrophages and monocytes, which are immune cells that help the body’s defense.

When these cells develop mutations, they proliferate faster than normal and become more inflammatory, potentially damaging body tissues. This condition, known as clonal hematopoiesis (CH), is detectable in 25% of people over age 70 and 50% of people over age 80, according to the researchers.

“We’ve discovered that healthy sleep and exercise can selectively influence immune cells with clonal hematopoiesis mutations, repressing their proliferative programming and expansion, as well as their ability to promote the formation of harmful plaque in the arteries of the heart,” said Cameron McAlpine, PhD, senior author of the study and associate professor of medicine (cardiology), and neuroscience at the Icahn School of Medicine at Mount Sinai, in a news release. “Surprisingly, our findings reveal that CH mutant cells are malleable and selectively responsive to lifestyle behavior in a way that can mitigate atherosclerotic risk.”

The research involved nearly 83,000 participants from the UK Biobank and 8,404 from All of Us, a dataset managed by the National Institutes of Health (NIH). The team also tested mouse models to evaluate how sleep fragmentation and exercise impacted CH caused by mutations in genes including Jak2, Tet2, p53, and Dnmt3a.

Researchers discovered that moderate-to-vigorous physical activity was associated with a reduced incidence of gene-specific CH and fewer mutant cells in the blood. Specifically, they found that sufficient sleep and exercise “turned off” the detrimental effects of Jak2 and Tet2 mutant CH hematopoietic stem cells, decreasing their ability to grow in a process known as clonal expansion.

“Our study showed that healthy sleep and exercise can counteract the harmful effects of certain age-related mutations which occur over time in the hematopoietic stem cells that produce our white blood cells,” said Teresa Gerhardt, MD, a postdoctoral fellow in the McAlpine Laboratory and lead author of the study, in a news release. “Significantly, we found that a healthy lifestyle can mitigate CH clonal expansion and the atherosclerotic consequences of CH mutations, making mutant cells behave like healthy, nonmutated cells.”

The study also examined macrophages, which are immune cells that normally destroy germs or damaged cells. Macrophages with a CH mutation, specifically in the Jak2 gene, were found to increase atherosclerotic lesions. However, scientists learned that healthy sleep repressed cell death and inflammatory pathways in Jak2 mutant macrophages by limiting CLEC4E signaling. Exercise had a similar effect by inducing sympathetic ADRB2 signaling from the brain to the mutant macrophages, decreasing inflammation and lesion size.

The researchers noted that while healthy sleep and exercise are recommended for all patients, they are especially important for those with Jak2 and Tet2 mutations. The team plans to develop therapeutics that can modulate signaling pathways to target mutant cells in people with Jak2 CH.

“The malleability of CH mutant cells means we can harness new signaling pathways to shut off the detrimental proliferative and inflammatory functions of those cells, while maintaining the function of healthy neighboring nonmutant cells,” said McAlpine, in a news release.