Helping the heart to age healthily

Aging is the biggest risk factor when it comes to heart health: even if all other indicators are kept at optimal levels, the risk of developing cardiovascular diseases increases with aging. Mahmoud Abdellatif and his team are seeking to find out why this is the case. As part of a project recently awarded an FWF ASTRA grant, they are analysing tens of thousands of samples to discover what happens to the heart as we age and which of these processes are particularly harmful. In this interview, Mahmoud Abdellatif talks about the project, his team’s research methods and his hopes for the future of his research.

Could you give us an overview of the project that was awarded the FWF ASTRA Prize?

In our ASTRA project, we aim to answer the question of how the heart ages by identifying the molecular factors that drive cardiac aging. The team is analysing samples from tens of thousands of people, looking for clues as to which mechanisms and substances promote cardiac aging. To do this, the team is using newly developed technologies that enable them to detect and analyse thousands of proteins in the blood. The team then uses clinically relevant experimental models to investigate how these proteins and changes contribute to cardiac ageing. 

What methods does your team use in its research?

We have access to a range of research databases through which we can view data from around 15,000 individuals. In addition, we can validate our findings using data from Biobank UK, where we also have access to data from a further 50,000 or so participants, giving us a total pool of around 65,000 people. Using state-of-the-art analytical methods, we look for factors and proteins that increase with aging, and then identify which of these factors are actually linked to cardiovascular health. To find this out, we use experimental models and can block or inhibit proteins and silence certain genes to see whether an improvement occurs or positive effects can be observed.

What is the preliminary aim of the research? What do you hope to discover?

The aim is, of course, to be able to identify the factors that drive cardiac ageing. Once we know these factors, it may be possible to develop therapies and medications that can slow down or halt these ageing processes. So we want to lay the foundations on which further research into cardiac ageing can build. 

A particular focus is on what is known as autophagy. This is a natural self-cleansing process within cells, during which damaged cell components and waste products are broken down and recycled. This helps to maintain the cells’ functionality. This process is of particular importance in the heart. Heart muscle cells hardly divide at all after birth and have only a very limited capacity for regeneration. They must therefore remain functional throughout a person’s lifetime. If we succeed in maintaining or specifically promoting autophagy in the aging heart, this could represent a promising approach to maintaining heart health well into old age.

In previous research, we identified certain substances and receptors that were particularly important for the ageing of the heart. The IGF1 signalling pathway, for instance, had already been the focus of my research. Using a mouse model, we were able to demonstrate that an increased IGF1 signalling pathway in youth led to better cardiac function, but to poorer outcomes during aging and earlier death, whilst mice that had reduced IGF1 activity in their youth initially suffered from poorer cardiac function but were later fitter and lived longer. The aim, therefore, is to find substances that keep our hearts fit during aging and, ideally, target only heart cells. This is a major challenge that we intend to tackle.

Let’s take a look into the future. How can the research you are conducting as part of this project help people?

Aging is one of the most important factors when it comes to the risk of developing diseases. In the case of cardiovascular diseases in particular, the patient’s age is a major risk factor. There are, of course, other well-known risk factors such as diabetes, obesity, high cholesterol levels and many more, but Aging has the greatest impact, and so far we have not found a way to reduce this impact.