They identify an anti-aging gene in a group of centenarians that regresses the biological age of the heart by 10 years and has become a potential therapeutic target to treat patients with heart failure. The finding is the result of a study conducted by researchers at the University of Bristol and the MultiMedica Group in Italy, which has been published in Cardiovascular Research.
Healthy mutant genes are associated with exceptional longevity and their carriers often live 100 years or more and enjoy good health. In addition, they are less likely to develop cardiovascular problems, and scientists believe the gene helps keep their hearts young and protects them against age-related diseases such as heart failure.
The authors of the new study have found that one of these healthy mutant genes, previously shown to be especially common in centenarians, can protect cells from heart failure patients requiring heart transplantation. The Bristol team, led by Professor Paolo Madeddu, discovered that a single administration of the mutant anti-aging gene halted the decline in heart function in middle-aged mice.
What was even more surprising, however, was that when given to elderly mice, whose hearts exhibited the same abnormalities seen in elderly patients, the gene turned back the age of the heart’s biological clock by the human equivalent of more of ten years
Professor Madeddu, Professor of Experimental Cardiovascular Medicine at the University of Bristol Heart Institute and one of the study authors, explained: “The function of the heart and blood vessels comes into play as we age. However, The speed at which these harmful changes occur is different between people. Smoking, alcohol and sedentary living speed up the aging clock. While eating right and exercising slow down the heart’s aging clock.”
“Also, having good genes inherited from your parents can help you stay young and healthy. Genes are sequences of letters that code for proteins. By chance, some of these letters can mutate. Most of these mutations are insignificant; in some cases, however, the mutation can make the gene work worse or better, such as in the mutant antiaging gene that we have studied here in older human cells and mice.”
Healthy anti-aging genes that are passed on to offspring
The three-year study was also carried out with human heart cells in the laboratory in Italy, where scientists from the MultiMedica Group in Milan, led by Professor Annibale Puca, administered the gene into heart cells from elderly patients who had severe problems. including transplantation, and then compared their function with that of healthy individuals.
Monica Cattaneo, a researcher at the MultiMedica Group in Milan, Italy, and first author of the paper, said: “Cells from elderly patients, particularly those that support the construction of new blood vessels called ‘pericytes,’ were found to have less By adding the longevity gene/protein to the test tube, we observed a process of cardiac rejuvenation: heart cells from elderly heart failure patients have returned to function properly, proving to be more efficient at building new blood vessels.
Centenarians pass on their healthy genes to their offspring, and the study shows for the first time that a healthy gene present in centenarians could be transferred to unrelated people to protect their hearts. Other mutations could be found in the future with a potential for a cure similar to, or even greater than, the one investigated by these scientists. Professor Madeddu and Professor Annibale Puca of the MultiMedica Group believe that their work can drive new treatments inspired by the genetics of centenarians.
Professor Madeddu added: “Our findings confirm that the healthy mutant gene can reverse the decline in cardiac performance in older people. We are now interested in whether giving the protein in place of the gene can also work. Gene therapy is widely used to treat diseases caused by defective genes. However, a protein-based treatment is safer and more feasible than gene therapy.”
“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 premature aging damage to the heart and blood vessels of children. It has also been funded by the British Heart Foundation and Diabetes UK to test the protein in elderly and diabetic mice, respectively.”
Annibale Puca, Head of Laboratory at IRCCS MultiMedica and Professor at the University of Salerno, concludes: “Gene therapy with the healthy gene in mouse models of disease has already been shown to prevent the onset of atherosclerosis, vascular aging and diabetic complications, and to rejuvenate the immune system. “We have a new confirmation and extension of the therapeutic potential of the gene/protein. We look forward to testing its effectiveness soon in clinical trials in patients with heart failure.”
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