Researchers from the universities of Porto and Coimbra have discovered a new therapeutic approach with the potential to transform the treatment of heart failure with preserved ejection fraction (HFpEF), one of the most complex and disabling forms of this disease. By eliminating aged cells from the heart and the immune system, it was possible to reverse symptoms and improve cardiac function, paving the way for the application of rejuvenation medicine to cardiovascular conditions.
The study, published in the prestigious journal Cardiovascular Research, used an animal model that mimics human HFpEF in a cardiometabolic setting. During the research, the scientists observed an accumulation of senescent cells — aged cells that no longer divide but continue to release harmful inflammatory substances — in the immune system, blood vessels and cardiac tissue.
The administration of a senolytic drug, able to eliminate these dysfunctional cells, proved effective in relieving multiple HFpEF symptoms at once. The benefits recorded include significant improvements in cardiovascular health and overall functional status, indicating that the targeted removal of senescent cells could represent a new therapeutic weapon.
"We are transforming the paradigm of cardiovascular therapy: it is not just about relieving symptoms, but about acting directly on the cellular mechanisms of ageing", says Elsa Silva, a researcher at the Institute for Research and Innovation in Health of the University of Porto (i3S) and first author of the article.
Inês Tomé, of the Centre for Neuroscience and Cell Biology of the University of Coimbra (CNC-UC), reinforces that the study "shows that it is possible to intervene directly in the cellular mechanisms of ageing to treat highly disabling diseases".
The coordinator of the team at i3S and the Abel Salazar Institute of Biomedical Sciences (ICBAS), Diana S. Nascimento, stresses the direct impact of this intervention on cardiovascular and systemic health. Lino Ferreira, leader of the team at CNC-UC/CIBB and the University of Coimbra Faculty of Medicine, highlights "the enormous potential of rejuvenation medicine as a therapeutic approach to complex, multifactorial diseases such as HFpEF".
According to the researchers, high levels of senescent leukocytes (aged immune cells) were also identified in HFpEF patients, associated with more severe forms of the disease, which reinforces the clinical value of the proposed approach.
The work now published "represents a milestone in the convergence of anti-ageing and cardiovascular medicine", note the authors, who also highlight the collaboration between three outstanding Portuguese scientific institutions as decisive for this advance.
With HFpEF gaining ground among the ageing population and associated with comorbidities such as hypertension, diabetes and obesity, the teams are already preparing the next steps: studying the mechanisms of premature cardiovascular ageing and developing personalised therapies, with a view to the clinical translation of this innovative discovery.
The consequences of HFpEF are serious and include extreme fatigue, difficulty carrying out simple everyday tasks and a mortality rate comparable to that of several types of cancer. Its rapid increase represents, according to i3S, "one of the greatest challenges of contemporary cardiovascular medicine".
