Scientists uncover heart ageing mechanism that can lead to cardiovascular disease

A study conducted by an international research team, in collaboration with the University of Coimbra (UC), reveals new information about the heart’s natural ageing mechanism, which may potentially impact the onset of cardiovascular diseases. The scientists believe that this discovery may, in the future, contribute to new methods for the early diagnosis of cardiovascular diseases, as well as to the development of therapies for the prevention of these pathologies.

The results of this discovery are presented in the scientific article Cardiac Molecular Analysis Reveals Aging-Associated Metabolic Alterations Promoting Glycosaminoglycans Accumulation via Hexosamine Biosynthetic Pathway, published in the journal Advanced Science, with contributions from three researchers from the UC Centre for Neuroscience and Cell Biology (CNC-UC) and the Centre for Innovative Biomedicine and Biotechnology (CiBB): Luís Grilo (first author of the study), Paulo Oliveira, and Susana Pereira (senior authors).

It is well known that heart-related diseases are more prevalent in older age; however, it is unclear how exclusively physiological ageing – that is, ‘natural’ ageing, which particularly results in the decline of certain physical and cognitive abilities and the loss of organic functions, leading to disease – affects heart function. In this context, UC researchers emphasise that “knowing the first symptoms of cardiac ageing may be relevant for the early detection and prevention of cardiac dysfunction”.

Against this backdrop, the research team sought to identify the cascade of molecular mechanisms responsible for the relationship between the natural ageing of the heart and cardiac dysfunction, using healthy non-human primate models with physiology very similar to that of the human heart.

The scientists were able to “identify that the cardiac adaptations derived from ageing begin with metabolic changes in the heart cells,” they point out. More specifically, they observed that “with age, the heart uses more glucose for the synthesis of molecules, which accumulate in the walls of the heart during ageing. In an initial phase, this accumulation promotes the stiffening of the heart walls and, in a second phase, cardiac hypertrophy,” explain Luís Grilo, Paulo Oliveira, and Susana Pereira. “These two consequences are directly related to the development of cardiovascular diseases,” stresses the team from the University of Coimbra.

Cardiovascular diseases are currently the leading cause of death worldwide. In addition to this significant impact on mortality, “a substantial number of people with this type of condition require specific and ongoing care—such as tests and medication—which results in high costs for the individual and for health systems,” the researchers report.

In this context, the discovery presented in this study could contribute to improving diagnosis and, consequently, reducing mortality. “By identifying molecular events that occur naturally in the heart before the onset of heart disease, as we did in this study, we open the door to the development of new methods for early diagnosis, preventing deaths and reducing the costs associated with the diagnosis and treatment of cardiovascular diseases,” say Luís Grilo, Paulo Oliveira, and Susana Pereira.

The research team from the University of Coimbra states that this study could pave the way for the “development of non-invasive methods to detect the accumulation of molecules in the human heart, thus improving current diagnostic techniques.” “It will also be crucial to investigate and test new pharmacological approaches in the future that can prevent the accumulation of molecules in the walls of the heart and, consequently, prevent its stiffening,” say Luís Grilo, Paulo Oliveira, and Susana Pereira.

Researchers from several universities based in the United States—Wake Forest University School of Medicine, the University of Wyoming, and the University of Texas—as well as the Texas Biomedical Research Institute also participated in this study. The Faculty of Sport of the University of Porto also collaborated on the research.

The scientific article is available here.