When the heart loses its nerves

How do nerves and blood vessels interact in the aging heart? New light on aging processes in the heart

31-Aug-2023 - Germany

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Why does the aging heart often lose its rhythm? It is above all the left ventricle that pumps blood through the body’s circulatory system, but over the course of a lifetime it starts to show signs of aging: It enlarges and can sometimes form scar tissue, which compromises its pumping function. The study “Aging impairs the neurovascular interface in the heart” by the Institute of Cardiovascular Regeneration and the Cardio-Pulmonary Institute of Goethe University Frankfurt together with the German Center for Cardiovascular Research (DZHK) demonstrates for the first time that changes occur in the left ventricle at the interface of blood vessels and the nervous system in old age: The nerves degenerate. It is then more difficult for the heart to react with the heart rate, the pulse, to corresponding demands when under stress. It loses its rhythm, as it were. The researchers’ findings have now been published in the journal Science.

The research team led by Professor Stefanie Dimmeler and postdoctoral researcher Dr. Julian Wagner examined the interaction between the nervous system and blood vessels in the heart. While it has been known for some time that the function of blood vessels supplying the heart declines with age, it was so far unknown whether the aging process could also influence their interaction with the nerves in the heart. The team has now been able to corroborate that the nerves in an aging heart degenerate. This reaction is triggered by blood vessels in the heart releasing, with increasing age, the messenger substance semaphorin-3A, inter alia, into their immediate environment, which inhibits the growth and sprouting of nerve cells in the cardiac muscle tissue. The outcome of this reduced nerve density in the heart itself is that the cardiac muscle cells are no longer “informed” by impulses from the nerve cells, for example a faster heartbeat telling them to supply more oxygen to the body when under stress. This leads to the heart losing some of its autonomous control over heart rate, which might possibly also have long-term adverse consequences for survival, as clinical observations suggest.

What seem to play a central role in the decline of nerve cells in the heart are aging, ‘senescent’ cells of the vascular system. Experiments have shown that if targeted drugs (known as senolytics) are used to restrict the number of these ‘senescent’ cells, the nerve cells grow again and the heart regains autonomous control over pulse regulation. However, future studies will have to show to what extent this type of therapy can be transferred to humans.

With their findings on the disrupted interaction of blood and nerve cells in the heart tissue, which goes hand in hand with increasing age, the researchers in Frankfurt are highlighting an important part of heart research that has so far largely been disregarded.

The Institute of Cardiovascular Regeneration, the Cardio-Pulmonary Institute of Goethe University Frankfurt (CPI) and the German Center for Cardiovascular Research (DZHK) point out that these findings contribute to an understanding of cardiovascular health in conjunction with the aging process. In their opinion, this research constitutes an important step toward a better understanding of the complex mechanisms underlying heart diseases. The knowledge acquired could potentially open up new approaches to the prevention and treatment of cardiovascular diseases.