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Ruggiero Corcella
An international study coordinated by the Sant’Anna School of Advanced Studies in Pisa and published in Science Translational Medicine demonstrates that preserving, or restoring, the vagal innervation of the heart can prevent cardiac aging processes. New perspectives for transplant surgery
The heart is not just a mechanical pump, but an organ finely regulated by the autonomic nervous system. In this continuous dialogue between brain and heart muscle, the vagus nerve plays a central role. It is precisely this “heart-brain axis” that is at the center of an international study coordinated by the Scuola Superiore Sant’Anna of Pisa, which demonstrated how the loss of vagal innervation accelerates the aging of the heart and how its restoration can instead protect it. The research, published in the journal Science Translational Medicineindicates that the right cardiac vagus nerve acts as a true gatekeeper of cardiomyocyte health, regardless of heart rate.
Multidisciplinary approach
The study is characterized by a highly multidisciplinary, integrating approach experimental medicine e bioengineering applied to cardiovascular research. In particular, the research was guided byTranslational Critical Medicine Unit (TrancriLab) del Interdisciplinary Health Science Research Centerunder the responsibility of the professor Vincenzo Lionettiand from the laboratory ofInstitute of Biorobotics led by the professor Silvestro Micerawhich contributed to the development of the bioabsorbable nerve conduit used to facilitate vagal regeneration.
Early remodeling
Sectioning or damage to the vagus nerve can occur during thoracic surgery, cardiac surgery or transplants. The study shows that this loss of connection is not neutral: the heart undergoes premature remodeling, with typical signs of cellular aging. “When the integrity of the connection to the vagus nerve is lost, the heart ages more rapidly,” he explains Professor Vincenzo Lionettihead of the study.
A statement that is confirmed by experimental data: without vagal innervation, oxidative stress, fibrosis and mechanical dysfunction of the heart increase.
The experimental model: the heart of the minipig
To arrive at these conclusions, the researchers used an animal model particularly close to humans: the adult minipig. After the section of the right vagus nerve at the cardiac level, a part of the animals was treated with an innovative bioabsorbable nerve conduit, designed to drive nerve regeneration. The comparison between treated and untreated animals allowed us to observe, over time, the evolution of cardiac function through magnetic resonance imaging, histological analyzes and in-depth molecular studies.
Repair the nerve to save the heart
The key result is that also partial restoration of the vagal connection is sufficient to protect the heart. «The restoration, even partial, of the connection between the right vagus nerve and the heart is sufficient to counteract the remodeling mechanisms and preserve effective cardiac contractility», he comments Pomegranate Dushpanovafirst author of the study. In treated minipigs, left and right ventricular function remains stable over timewhile progressive signs of dysfunction appear in untreated animals.
Bioengineering at the service of medicine
A decisive contribution comes from bioengineering. The group from the Sant’Anna Biorobotics Institute has developed a bioabsorbable nerve conduit capable of promoting the spontaneous regeneration of the thoracic vagus nerve. «We have developed an implantable bioabsorbable nerve conduit designed to promote and guide the spontaneous regeneration of the thoracic vagus nerve at the cardiac level», he explains Eugenio Redolfi Rivaco-author of the patent. This device allows nerve fibers to recolonize the heart, restoring balance between the sympathetic and parasympathetic systems.
Less oxidative stress, less inflammation, less senescence
At the cellular level, the “renervated” heart shows fewer signs of premature aging. Markers of oxidative stress and senescence decrease, inflammation is reduced and the structure of the cardiac tissue is preserved. On the contrary, in hearts lacking vagal innervation, fibrosis, macrophage infiltration and molecular alterations typical of advanced age increase. The vagus nerve, therefore, does not simply modulate the heartbeat, but activates actual biological protection mechanisms.
New clinical perspectives
Taken together, these results open up new scenarios for clinical practice. «These results open new perspectives for cardiothoracic and transplant surgery», concludes Lionetti, «suggesting that the restoration of cardiac vagal innervation at the time of surgery may represent an innovative strategy to protect the heart in the long term». The objective is no longer just to manage the late complications of cardiac aging, but to prevent them by intervening on that invisible thread – the vagus nerve – which unites the brain and heart.
A network of excellence
The experimental activity was carried out in Pisa thanks to a European FET financing (Future and Emerging Technologies) within the framework of the «NeuHeart» project and, in part, with the support of the PNRR del Tuscany Health Ecosystem. The study involved a large network of Italian and international institutions of excellencesuch as the Scuola Normale Superiore, the University of Pisa, the Fondazione Toscana G. Monasterio, the Institute of Clinical Physiology of the CNR, the University of Udine, GVM Care & Research, the Al-Farabi Kazakh National University, the Leibniz Institute on Aging of Jena and the École Polytechnique Fédérale de Lausanne.
December 30, 2025
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