Mechanism underlying the relationship between aging, stress and heart attacks discovered

The results of their study have recently been published in the renowned scientific journal PNAS. First author Anthony Zannas and his colleagues evaluated the data of more than 3,000 volunteers aged between 18 and 87 years.

They demonstrated that epigenetic changes caused by stress and aging are associated with immune changes that are decisive for inflammatory processes in cardiovascular diseases. Higher stress levels and aging together led to epigenetic changes that promoted inflammation and increased risk of having a heart attack.

The epigenetic effect of stress and aging was reflected in the reduction of the so-called DNA methylation of the gene FKBP5. The protein it codes, which is involved in stress physiology, is stronger transcribed through this process. The authors found that stronger transcription leads to an increased inflammatory reaction through activation of the important immune regulator NF-kB.

This in turn can contribute to increased risk of cardiovascular diseases. “The epigenetic changes triggered by aging and stress and the associated alterations in immune function can be a risk factor for inflammation and heart attacks,” Zannas sums up. In other words, patients who had a heart attack show exactly the same epigenetic changes that are caused by increased stress and accelerated aging.

The Max Planck researchers also verified the reverse effect at the cellular level: Inhibition or deletion of FKBP5 in cultured immune cells inhibited the alterations in NF-kB signaling.

Novel treatment offers

The results suggest that epigenetic effects caused by aging and stress accelerate inflammatory processes. They might therefore play a decisive role in the development of cardiovascular diseases. “We were able to identify a mechanism that might explain the increased incidence of cardiovascular diseases in patients with stress-related psychiatric diseases,” says Elisabeth Binder, Director at the Max Planck Institute of Psychiatry.

The epigenetic modifications described here and the changes in the immune system might serve as biomarkers and help to identify people at an increased risk of diseases, such as heart attacks. The research into the correlations between stress, aging and heart diseases respectively epigenetic changes and inflammatory processes may lead to novel treatments for stress-related diseases.

https://doi.org/10.1073/pnas.1816847116