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Professor Paolo Madeddu and his team are working to delay the ageing of the heart. He tells Dr Leanne Grech how this research could allow older people to live a healthier life for longer.

Each day, your heart beats around 100,000 times, pumping about eight pints of blood around your body. By the time you are 20, the heart’s function can begin to decline as part of normal ageing. As you get older, activities like running or playing tennis become more difficult. However, some 100-year-olds, like those living in Okinawa, a cluster of islands in southern Japan, appear to have unlocked the secret to a long and healthy life, with some of them seemingly having a heart younger than their age. “It’s a combination of a good lifestyle and good genes,” explains Professor Paolo Madeddu at the University of Bristol. “And we have discovered that one of these good genes can stop ageing.”

The gene that can stop ageing Professor Madeddu and his team have discovered that a naturally occurring variant of the BPIFB4 gene, which is more common in people who live to 100 or more, could help keep the heart young. A gene variant is a permanent change in the DNA sequence that makes up a gene. The team have already learned that mice treated with this variant have healthier hearts. In fact, transferring this gene variant to old mice seemed to help relax blood vessels in mice with high blood pressure and increase the amount of blood delivered to the muscles. In humans, ageing can affect many parts of the body, including weakening the heart and circulatory system. For example, heart failure, a serious and sometimes disabling condition for which there is no cure other than a heart transplant. Symptoms include breathlessness and feeling abnormally tired. Heart failure can occur at any age, but it is more common in older people, and in people who have had a heart attack and who have cardiomyopathy or high blood pressure.

Scientists are now beginning to understand how some natural variations in our genes might protect against heart diseases linked to ageing, such as heart failure. In this study, Professor Madeddu and his team in Bristol have been funded by the BHF with more than £172k to further investigate the role of the BPIFB4 gene variant. The BPIFB4 gene has been associated with exceptional longevity, helping protect against atherosclerosis (build-up of fatty material inside your arteries) and high blood pressure. The team now want to know if this gene variant can be given as a tablet and if it can reduce chronic inflammation (a damaging set of processes often seen in ageing hearts). Most genes contain the information needed to make functional molecules called proteins. Giving the corresponding protein as a pill instead of the gene variant could be an easier way to get the same result. Professor Madeddu and his team will test this idea in mice. If it succeeds, they hope to go on to a clinical trial in humans. “The study will provide proof of concept that our solution is valid. More studies are needed to show it is also safe – the fact that it is a human protein and not a [new] drug is encouraging. However, producing large quantities of protein is extremely expensive, and we will need investors or an industrial partner in the future. The BHF could help us to find the right partner,” explains Professor Madeddu.

Helping older hearts Professor Madeddu is a cardiologist by background, and has been fascinated by the heart since he was a medical student. “Research requires a lot of determination and effort. I hope that the results of my work can make a difference in the lives of a lot of patients.” In 2021, around 12.5 million people in the UK were 65 or older. Life expectancy had been rising for decades, but the increases have slowed since 2010, and life expectancy for both men and women has fallen since the Covid-19 pandemic. Research like that of Professor Madeddu aims to help older adults stay healthy and independent for longer, which is among the UK Government priorities. “There is no current treatment to stop the heart’s ageing, and drugs used for heart disease can cause side effects in seniors,” explains Professor Madeddu. “We hope that giving older people a protein that is present in healthy centenarians, like those in Okinawa, helps their hearts work better for longer. Our approach proposes to increase health rather than simply combat disease. If we can find an effective treatment to delay ageing of the heart, we may be able to prevent serious disease in older people.”

Read the case report

Monica Cattaneo ¹ , Antonio P Beltrami ² , Anita C Thomas ³ , Gaia Spinetti ¹ , Valeria Alvino ³ , Elisa Avolio ³ , Claudia Veneziano ² , Irene Giulia Rolle ² , Sandro Sponga ² , Elena Sangalli ¹ , Anna Maciag ¹ , Fabrizio Dal Piaz ⁴ , Carmine Vecchione ^4,5 , Aishah Alenezi ⁶ , Stephen Paisey ⁶ , Annibale A Puca ^{1  4} , Paolo Madeddu ³  The longevity-associated BPIFB4 gene supports cardiac function and vascularization in aging cardiomyopathy.  Cardiovasc Res. 2023 Jan 13;cvad008. PMID: 36635236 DOI: 10.1093/cvr/cvad008.

Researchers at the University of Bristol, funded by the British Heart Foundation (BHF), have developed ‘stem cell plasters’ to revolutionise the way surgeons treat children living with congenital heart disease, so they don’t need as many open-heart operations.

Professor Andy Judge, Head of Section for Cardiovascular Surgery and Vascular Biology, reflects on recent successes.

With the new academic year underway, we welcome our new cohorts of postgraduate taught master’s degree students for the MSc in Perfusion Science and the MSc in Translational Cardiovascular Medicine (TCM). The teaching sessions are now back in person for the campus based TCM students and Perfusion students, and our student numbers are good.

I’m pleased to report that the labs, which closed for three months at the start of the pandemic, have been open since June 2020. Staff are gradually returning to the office at Level 7 of the BRI as the University has launched its blended working trial policy, and we are now seeing more staff in both the labs and offices.

Within our section for Cardiovascular Surgery and Vascular Biology at the University, we are delighted to have been able to appoint staff to new posts. Dr Kerry Wadey has been appointed as Lecturer in Cardiovascular Medicine on an open-ended core funded post. Francesco Paneni has been appointed as a Professor in Cardiology and Tom Johnson as an Associate Professor in Cardiology and they are expected to begin working with us at the start of 2022.

A number of staff in our section have had success following the annual University promotions procedure. Jason Johnson has been promoted to Professor of Cardiovascular Pathology, and Umberto Benedetto becomes Professor of Cardiac Surgery. Staff from the Teaching and
Learning for Health Professionals (TLHP) programme have recently joined our department of Translational Health Sciences and come under
the umbrella of our cardiovascular section, where we are delighted to congratulate Andrew Blythe on being promoted to Professor of Medical Education in this year’s annual promotion procedure.

Huge congratulations to all those recently promoted: we wish them continued success in their careers.

Drs Lucy Culliford, Andrew Shearn and Giovanni Biglino took part in an outreach activity at Parson Street Primary School in Bedminster, south Bristol. in May 2021.

The visit was organised by Lucy on behalf of the Bristol Trials Unit. The group explained some of their research to the Year 6 students (aged 10 and 11) and, as the visit happened in the same week as Clinical Trials Day, it was also an opportunity for Lucy to ask the students to think about clinical studies, the idea of randomisation and ‘what is a clinical trial?’. The group showed the THERMIC 3 animation video, which was developed as part of the TRECA study exploring children’s and young people’s engagement with clinical trials.

Giovanni gave an overview of the technology involved in 3D printing and Andrew brought a series of heart models, both adult and paediatric, including examples of babies’ hearts with congenital heart disease, which sparked some stimulating conversations with the 53 students who attended.

They explained that 3D printing technology can produce models of human organs using scans taken during routine visits to the hospital. Bristol Royal Hospital for Children use this technique to create heart models from patients with congenital heart disease. Being able to hold a life-size model of the patient’s heart can complement information the surgeon or cardiologist can get from medical imaging – for example, they can practice aspects of the surgery or decide the best route to access a specific part of the heart. The models are also used when explaining the details of the case to a patient or a parent.

The children asked lots of questions about ‘hole in the hearts’, as some had had siblings with this condition. They also asked how smoking can affect the heart, and if the researchers could show them a video of a beating heart.

Lucy said:

“This is the first time we’ve done a talk in a school as part of our outreach activities around Clinical Trials Day, and it was a real pleasure to talk to the children. They were very engaged and although they had only started learning about the heart the day before, they already knew lots about heart anatomy, and had more questions than we had time to answer!”

How to get involved in schools outreach

If you would like to run a schools outreach activity, contact your local school.

Schools often have science weeks, or may be doing a topic related to cardiovascular research. For example, Parson Street Primary School use the Cornerstones curriculum and the year 6s had just started the ‘blood heart’ topic – the following week they had a visitor demonstrating a heart dissection.