A team of researchers from the Center for Neuroscience and Cell Biology at the University of Coimbra (CNC-UC), part of the Centre for Innovative Biomedicine and Biotechnology (CiBB), together with the Institute for Research and Innovation in Health at the University of Porto (i3S), has made a discovery that could transform the future of cardiac medicine. Through an innovative strategy inspired by rejuvenation medicine, scientists have found a way to combat one of the most serious variants of heart failure, heart failure with preserved ejection fraction (HFpEF).
In this study, published in the prestigious journal Cardiovascular Research, the researchers used an animal model that mimics human HFpEF in a cardiometabolic context and observed an accumulation of senescent cells in the immune system, blood vessels, and heart. These are aged cells that have stopped dividing but remain in the body and release inflammatory substances that damage neighboring tissue cells, accelerating the aging process and contributing to the development of disease.
"This work highlights the enormous potential of rejuvenation medicine as a therapeutic approach for complex and multifactorial diseases such as HFpEF", explains the researcher who leads the team at CNC-UC/CIBB and the Faculty of Medicine of the University of Coimbra, Lino Ferreira.
"After administering a senolytic drug, which specifically eliminates these senescent cells, we observed simultaneous relief of the multiple symptoms of HFpEF, meaning there is a direct impact on cardiovascular and systemic health", says Diana S. Nascimento, coordinator of the i3S and ICBAS team.
"For decades, we have viewed aging as an inevitable process. This study shows that it is possible to intervene directly in the cellular mechanisms of aging to treat highly debilitating diseases", adds CNC-UC/CiBB researcher Inês Tomé.
The researchers also point out that high levels of senescent leukocytes (blood cells in our immune system) in circulation were observed in patients with HFpEF and were associated with greater disease severity, suggesting that this approach may have direct clinical relevance.
"We are transforming the paradigm of cardiovascular therapy: it is not just a matter of alleviating symptoms, but of acting directly on the cellular mechanisms of aging, which are at the root of age-related organ dysfunction", concludes the i3S researcher and first author of the article, Elsa Silva.
The authors emphasize that the work "represents a milestone in the convergence of anti-aging and cardiovascular medicine, made possible only through strong collaboration between three leading Portuguese institutions in cardiovascular research, regenerative medicine, and aging: i3S, CNC-UC/CIBB, and the Faculty of Medicine of the University of Porto."
The teams are already planning the next steps to evaluate the mechanisms that cause premature aging in a cardiovascular context and develop new, more personalized therapies with a view to their future clinical translation.
HFpEF is one of the greatest challenges in contemporary cardiovascular medicine. This form of heart failure is increasing at an alarming rate and, due to the aging population, is expected to become dominant in the near future. Its severity is compounded by the fact that it is often associated with other prevalent conditions, such as hypertension, diabetes, and obesity.
In this condition, although the heart retains its ability to pump blood, the left ventricle loses the flexibility necessary to relax and fill properly. The consequences are devastating shortness of breath, incapacitating fatigue, limitation in simple daily tasks, and, above all, a mortality rate comparable to that of several types of cancer.
i3S with CNC-UC
