Healthy sleep and exercise reduce the risk of heart disease

This condition is called clonal hematopoiesis (CH). According to scientists, it is found in a quarter of people over 70 years of age and in half of people over 80 years of age. CH is rare in young, healthy people.

A team from the Icahn Mount Sinai School of Medicine’s Cardiovascular Research Institute conducted a large-scale study. It was attended by almost 83,000 people from the British Biobank (UK Biobank) and 8,404 participants of the All of Us project, whose data is collected by the US National Institutes of Health. Additionally, the scientists tested the models on mice. They evaluated the effects of sleep fragmentation and physical activity on CH caused by mutations in the Jak2, Tet2, p53, and Dnmt3a genes.

Moderate and intense physical activity is associated with a decrease in the frequency of gene-specific CH and the number of mutant cells in the blood. Adequate sleep and exercise disable the harmful effects of mutant Jak2 and Tet2 hematopoietic stem cells in the bone marrow, reducing their ability to proliferate. A healthy lifestyle causes mutant cells to behave like healthy, non-mutated cells.

Macrophages are immune cells that live in tissues and typically destroy microbes, damaged cells, or cancer cells. When CH is mutated, they stop functioning properly and contribute to the development of cardiovascular diseases, including atherosclerosis.

The study found that healthy sleep suppresses cell death and inflammation pathways in Jak2-mutated macrophages. It limits the signaling of CLEC4E, a pathway that plays a key role in immune responses and inflammation. Exercise, on the other hand, activates the sympathetic signaling of ADRB2, which is involved in inflammation, from the brain to Jak2-mutated macrophages in atherosclerotic lesions. As a result, inflammation in these macrophages is reduced and the size of the lesions is decreased.

According to Dr. Cameron McAlpine, senior author of the study and an associate professor of medicine (cardiology) and neurology at the Icahn School of Medicine, mutant CH cells can be corrected through lifestyle changes. This can reduce the risk of atherosclerosis and preserve the functions of healthy neighboring cells. Healthy sleep and physical activity are especially important for people with Jak2 and Tet2 mutations.

Sinai plans to develop a therapy that modulates the CLEC4E and ADRB2 signaling pathways to target mutant cells in people with Jak2 CH. According to McAlpine, the flexibility of mutant CH cells means that new signaling pathways can be used to disable the harmful proliferative and inflammatory functions of these cells while preserving the healthy functions of healthy cells.

Dr. McAlpine notes that genetics can now be used not only to develop new treatments but also to adapt lifestyle management and therapy. Experts hope to identify people with genetic risk factors for cardiovascular diseases and advise them on steps to reduce this risk now.

Clonal hematopoiesis (CH) is a common age-related condition that increases the risk of atherosclerosis. Healthy sleep and moderate to intense physical activity reduce the activity of mutant cells, especially Jak2 and Tet2, and their inflammatory potential. The mechanisms include the suppression of CLEC4E pathways by sleep and the activation of ADRB2 by exercise. In the long run, this paves the way for personalized recommendations and new treatment methods.