An anti-ageing gene found in a population of centenarians may be able to rewind the heart’s age by ten years, according to a study published in the scientific journal Cardiovascular Research. The researchers from the University of Bristol, UK, and the MultiMedica Group in Italy, believe this could offer enormous potential to treat patients with heart failure and other cardiovascular problems.
In some areas in the world — called blue zones — people often live to 100 years or even older and remain in good health. These people also experience fewer cardiovascular complications. It is believed these people carry a mutant form of some genes that give them these special abilities. These genes protect their hearts against diseases linked to ageing, such as heart failure.
In this study, the researchers used one of these mutated genes — found frequently in elderly patients — to protect heart cells collected from patients with heart failure.
The first experiment was done with mice. A single administration of the mutant anti-ageing gene prevented the decay of heart function in middle-aged mice. Moreover, the gene was able to rewind the heart’s biological age by the human equivalent of more than ten years.
“The heart and blood vessel function is put at stake as we age. However, the rate at which these harmful changes occur is different among people. Smoking, alcohol, and sedentary life make the ageing clock faster. Whereas eating well and exercising delay the heart’s ageing clock,” said Professor Madeddu, Professor of Experimental Cardiovascular Medicine from Bristol Heart Institute at the University of Bristol and one of the study’s authors. “In addition, having good genes inherited from parents can help to stay young and healthy. Genes are sequences of letters that encode proteins. By chance, some of these letters can mutate. Most of these mutations are insignificant; in a few cases, however, the mutation can make the gene function worse or better, like for the mutant anti-ageing gene we have studied here on human cells and older mice.”
To confirm these results, the team moved on to use human cardiac cells collected from patients with severe heart problems and then compared their function with cells from healthy individuals. “The cells of the elderly patients, in particular those that support the construction of new blood vessels, called ‘pericytes,’ were found to be less performing and more aged. By adding the longevity gene/protein to the test tube, we observed a process of cardiac rejuvenation: the cardiac cells of elderly heart failure patients have resumed functioning properly, proving to be more efficient in building new blood vessels,” said Monica Cattaneo, a researcher of the MultiMedica Group in Milan, Italy, and first author of the work.
This work shows how a healthy gene found in centenarians can be used in patients with heart problems. The team believes this study may fuel a new wave of treatments inspired by the genetics of centenarians. “Our findings confirm the healthy mutant gene can reverse the decline of heart performance in older people. We are now interested in determining if giving the protein instead of the gene can also work. Gene therapy is widely used to treat diseases caused by bad genes. However, a treatment based on a protein is safer and more viable than gene therapy,” said Professor Madeddu. “We have received funding from the Medical Research Council to test healthy gene therapy in Progeria. This genetic disease, also known as Hutchinson-Gilford syndrome, causes early aging damage to children’s hearts and blood vessels. We have also been funded by the British Heart Foundation and Diabetes UK to test the protein in older and diabetic mice, respectively.”
It’s still very early-stage research, but this work could be the basis for a revolutionary way to treat people with heart failure and even stop heart problems from developing in the first place.
Cattaneo M, Beltrami A, Thomas A, Spinetti G, Alvino V, et al. (2023) The longevity-associated BPIFB4 gene supports cardiac function and vascularization in aging cardiomyopathy. Cardiovascular Research, cvad008, https://doi.org/10.1093/cvr/cvad008