Researchers from the universities of Porto and Coimbra have discovered a way to “rejuvenate the heart” by acting “directly on the cellular mechanisms of aging” to combat one of the most severe variants of heart failure, it was announced today.
The focus is on heart failure with preserved ejection fraction (HFpEF), which occurs when “the left ventricle loses the necessary flexibility to relax and fill properly,” as explained by the Institute for Research and Innovation in Health at the University of Porto (i3S).
“We are transforming the paradigm of cardiovascular therapy: it’s not just about alleviating symptoms but directly acting on the cellular mechanisms of aging, which are the root of age-related organ dysfunction,” states Elsa Silva, i3S researcher and first author of the article.
Inês Tomé, from the Center for Neuroscience and Cell Biology at the University of Coimbra (CNC-UC), part of the Center for Innovation in Biomedicine and Biotechnology (CIBB), notes that the developed study “shows that it is possible to intervene directly in the cellular mechanisms of aging to treat highly debilitating diseases.”
The researchers, in work published on Monday in the journal Cardiovascular Research, used an animal model that simulates 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 harm the cells of neighboring tissues, accelerating the aging process and contributing to the development of diseases,” describes the i3S.
After administering a senolytic drug, which eliminates senescent cells, the researchers observed “simultaneous relief of multiple HFpEF symptoms.”
“There is a direct impact on cardiovascular and systemic health,” says Diana S. Nascimento, coordinator of the team from i3S and the Abel Salazar Institute of Biomedical Sciences (ICBAS).
According to Lino Ferreira, leader of the team from CNC-UC/CIBB and the Faculty of Medicine of the University of Coimbra, the work “highlights the enormous potential of rejuvenation medicine as a therapeutic approach for complex and multifactorial diseases such as HFpEF.”
The researchers also point out that “elevated levels of senescent leukocytes (blood cells from our immune system) were observed in patients with HFpEF, being associated with greater disease severity, suggesting that this approach could have direct clinical relevance.”
They emphasize that the work “represents a landmark 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.”
The teams are already planning the next steps to “assess the mechanisms that cause premature aging in the cardiovascular context and develop new, more personalized therapies with a view to their future clinical translation,” reports the i3S.
The consequences of HFpEF include “shortness of breath, disabling fatigue, a limitation for simple daily tasks, and, above all, a mortality rate comparable to various types of cancer,” explains the i3S.
“This form of heart failure is increasing at an alarming rate, and due to the aging population, it is expected to become dominant in the near future,” it adds.
The severity of HFpEF “is compounded by its frequent association with other prevalent conditions, such as hypertension, diabetes, and obesity,” making this heart failure one of the “greatest challenges of contemporary cardiovascular medicine.”
