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Neurovascular interactions in the ageing heart

Nature Reviews Cardiology (2026)Cite this article

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Abstract

The global rise in life expectancy underscores the urgent need to extend healthspan and prevent age-related diseases. Cardiovascular disease is the leading cause of death worldwide, with ageing as a major non-modifiable risk factor. Ageing drives progressive vascular dysfunction and cardiac decline, including heart failure with preserved or reduced ejection fraction. Vascular cells are particularly vulnerable to ageing, resulting in structural and functional deterioration of the microvasculature and macrovasculature. Emerging evidence highlights that ageing also disrupts the neurovascular interface — an intricate axis between the nervous and vascular systems that governs cardiac function. Alterations to the neurovascular unit in the heart contribute to impaired autonomic regulation, increasing the risk of arrhythmias and heart failure. In this Review, we examine how neurovascular ageing shapes cardiac dysfunction and explore the therapeutic potential of targeting the cardiac neurovascular unit to mitigate cardiovascular ageing and promote resilience in ageing populations.

Key points

  • The nervous and vascular systems form closely interconnected interfaces that coordinate tissue homeostasis, neuroimmune communication and vascular integrity in both health and disease.

  • Vascular ageing causes endothelial dysfunction, which affects neurovascular signalling, leading to reduced cardiac innervation and electrical instability; these changes can be reversed by senolytic therapies targeting senescent cells.

  • The cardiac neurovascular unit mirrors mechanisms in the central nervous system, where nerves and blood vessels align and co-develop, regulated by neural activity and endothelial signals, to maintain cardiac function.

  • Heart–brain communication mediated by neurovascular and neuronal pathways regulates cardiac autonomic control, linking central neurodegenerative processes to peripheral cardiac innervation and function.

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Fig. 1: The cardiac neurovasculome.
Fig. 2: Age-related alterations in the cardiac neurovasculome.
Fig. 3: Ageing impairs the cardiac neurovascular unit.
Fig. 4: The ageing heart–brain axis.

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Acknowledgements

We thank H. Kujundzic (Goethe University Frankfurt, Germany) for providing fluorescence images of the cardiac neurovasculome. J.U.G.W. is supported by the Dr Rolf-M.-Schwiete Foundation (2021-002). J.U.G.W. and S.D. are supported by the German Research Foundation (SFB1366 No. 394046768). S.D. is supported by the European Research Council (GAP – 101053352, Neuroheart) and the German Research Foundation (SFB1531 No. 456687919, the Cluster of Excellence Cardiopulmonary Institute Exc2026/1).

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Authors and Affiliations

  1. Institute of Cardiovascular Regeneration, Goethe University Frankfurt, Frankfurt am Main, Germany

    Julian U. G. Wagner & Stefanie Dimmeler

  2. German Centre for Cardiovascular Research (DZHK), Frankfurt am Main, Germany

    Julian U. G. Wagner & Stefanie Dimmeler

  3. Cardiopulmonary Institute, Goethe University Frankfurt, Frankfurt am Main, Germany

    Julian U. G. Wagner & Stefanie Dimmeler

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  1. Julian U. G. Wagner
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  2. Stefanie Dimmeler
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Correspondence to Stefanie Dimmeler.

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Glossary

Cardiac neurovascular unit

A microscale concept describing the intimate structural and functional association between neurons, vascular cells (endothelial cells, pericytes and vascular smooth muscle cells) and the extracellular matrix at a given microvascular segment (arteriole, capillary or venule) in the heart.

Cardiac neurovasculome

A macroscale systems concept denoting the totality of all neurovascular units, including all vascular and nervous structures, in the heart.

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Wagner, J.U.G., Dimmeler, S. Neurovascular interactions in the ageing heart. Nat Rev Cardiol (2026). https://doi.org/10.1038/s41569-026-01260-4

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