Updated

Updated · Mount Sinai · Jun 10

Mount Sinai Finds Sleep, Exercise Cut Heart Risk From Mutant White Blood Cells in 83,000-Person Study

Updated

Updated · Mount Sinai · Jun 10

Mount Sinai Finds Sleep, Exercise Cut Heart Risk From Mutant White Blood Cells in 83,000-Person Study

Q: Your genes may increase heart risk, but which ones are resistant to diet and exercise?

The Mount Sinai study suggests the clearest lifestyle-resistant mutation is **DNMT3A**. In the mouse experiments, healthy sleep and exercise reduced clone growth and atherosclerosis driven by **Jak2** and **Tet2**, and also lessened atherosclerosis from **Trp53** loss, but they did **not** curb **Dnmt3a**-driven clone expansion or Dnmt3a-driven atherosclerosis. There is a nuance with **TP53/TRP53**. The research indicates sleep and exercise did not stop **Trp53** mutant clones from expanding, so that part of the biology appeared resistant. But those habits still reduced the resulting atherosclerosis, meaning the cardiovascular damage was not fully resistant in the same way as DNMT3A. By contrast, **JAK2** and **TET2** were notably responsive to lifestyle. The study found sufficient sleep and moderate-to-vigorous exercise could dampen inflammatory signaling, restrain harmful clonal behavior, and reduce plaque formation linked to those mutations. That is why the researchers say these mutant cells are more malleable than previously thought. More broadly, some inherited cardiovascular risks are also relatively less modifiable by lifestyle alone, such as **lipoprotein(a), or Lp(a)**, which is largely genetically determined. But within this specific clonal hematopoiesis study, the strongest answer to which gene was resistant to sleep and exercise is **DNMT3A**, with **TP53/TRP53** showing partial resistance.

3 articles · Updated · Mount Sinai · Jun 10

Nearly 83,000 UK Biobank participants and 8,404 All of Us volunteers showed healthy sleep and moderate-to-vigorous exercise were linked to lower cardiovascular risk from clonal hematopoiesis, age-related mutations in white blood cells.
The Nature study found those habits reduced gene-specific CH incidence and mutant-cell burden, especially for Jak2 and Tet2 mutations that drive inflammatory clonal expansion and atherosclerosis.
Mouse experiments showed sleep suppressed CLEC4E signaling and exercise activated ADRB2 signaling, selectively calming mutant macrophages, shrinking arterial lesions, and leaving neighboring nonmutant cells largely unaffected.
Clonal hematopoiesis is rare in younger healthy people but detectable in about 25% of people over 70 and 50% over 80, making the findings especially relevant for older adults.
Mount Sinai said the next step is developing therapies that target pathways such as CLEC4E and ADRB2 and using genetics to tailor lifestyle advice for people with elevated cardiovascular risk.