Some people age better than others, living much longer than average and staying healthy late in life. What if the key was simply in their DNA? A recent study published in the journal Cardiovascular researchreveals that it may indeed be possible to develop new therapeutic prospects for the fight against cardiac aging from the genetic code of centenarians. Researchers from Italy’s University of Bristol and the MultiMedica group began by observing that carriers of healthy mutant genes associated with exceptional longevity, such as those living in the planet’s famous “blue zones,” often live up to 100 years. year or more and stay healthy. These people are also less prone to cardiovascular complications, and the explanation for this may lie in the gene that codes for the BPIFB4 protein, specifically the Longevity Variant (LAV) of this gene, which helps keep their hearts young. such as heart failure.
Recall that we speak of heart failure when the heart loses part of its muscle strength and normal contractility. A team led by British Heart Foundation-funded researcher Professor Paolo Madeddu has revealed that one of these healthy mutant genes, previously found particularly in centenarians, can protect cells from heart failure patients requiring heart transplants. . He found that a single administration of a “mutant antiaging gene” halted the deterioration of heart function in middle-aged mice. When given to aged mice whose hearts showed the same changes seen in older patients, the gene was able to “wind back” the age of the heart’s biological clock to the human equivalent of ten years. The 3-year analysis was conducted in vitro and in vivo. In an in vitro study, transplanted heart cells from elderly patients with heart problems were compared with heart cells from healthy individuals.
An anti-aging gene has stopped the heart from deteriorating
Thus, ” the cells of the former, especially the cells that support the construction of new blood vessels called “pericytes”, have been shown to be less efficient and older. Monica Cattaneo, a researcher at the MultiMedica group, explains. ” By adding the lab-produced LAV-BPIFF4 protein to the middle of these cells, which corresponds to a variant common for centuries, we witnessed a real cardiac rejuvenation process: the pericytes of old and sick patients functioned properly again. , proves to be more effective in the formation of new blood vessels.. This result is consistent with what was observed in parallel with an in vivo assay performed on mice at the University of Bristol. By administering the LAV-BPIFF4 protein to old mice to promote rejuvenation and to middle-aged mice to prevent cardiac aging, the method confirmed its efficacy by improving vascularization and reducing fibrosis, two key aspects to assess the state of cardiac aging.
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” As we age, the function of the heart and blood vessels deteriorates. However, the rate at which these harmful changes occur varies from person to person. Smoking, alcohol and a sedentary lifestyle accelerate aging, while good food and exercise delay the heart’s aging clock. Also, having good genes inherited from parents can help keep you young and healthy. Genes are sequences of letters that code for proteins. Fortunately, some of these letters can mutate. Most of these mutations are insignificant, but in some cases a mutation can make a gene work worse or better, such as the mutant anti-aging gene we studied here in human cells and aged mice. », explains Professor Paolo Madedu, a specialist in experimental cardiovascular medicine at the Bristol Heart Institute. But it remains to be seen whether this healthy gene, found for centuries, can be passed on to unrelated people to protect their hearts, which could lead to a breakthrough treatment.
A new wave of treatments inspired by centuries of genetics
Importantly, this finding opens the door to the discovery of other beneficial mutations in the future with similar or greater therapeutic potential than those investigated in this study. Finally, the idea of developing a new wave of treatment for patients with heart problems was inspired by the genetics of the centenarians. ” Our findings confirm that a healthy mutant gene can prevent the decline in cardiac performance in the elderly. Now we want to see if replacing the gene with a protein can work. Gene therapy is widely used to treat diseases caused by bad genes, but protein-based treatment is safer and more effective than gene therapy. We received funding to test a healthy gene therapy for Hutchinson-Gilford syndrome, more commonly known as progeria. We were also funded to test the protein in aged and diabetic mice, respectively.. »
In light of these results, Professor James Leyper, Medical Director of the British Heart Foundation, said: ” we all want to know the secrets of aging and how we can slow down age-related diseases. Our heart function declines with age, but this study has shown that a variant of a gene common in long-lived people can stop or even reverse heart aging in mice. It’s still early-stage research, but it could one day provide a revolutionary way to treat people with heart failure and even prevent the development of the debilitating disease in the first place. As for the “blue zones”, there are at least five of these amazing places that scientists are interested in because of their excellent health conditions: the province of Nuoro in Sardinia, the island of Ikaria in Greece, the island of Okinawa in Japan, the Nicoya Peninsula in Costa Rica, and the community in Loma Linda, California.
Annibale Puca, head of the IRCCS MultiMedica laboratory and professor at the University of Salerno, is among those who have focused their research on the study of the DNA of centenarians and contributed to the update of the fact that the LAV variant is more frequent. the latter and is negatively correlated with the degree of cardiovascular involvement. “ In mouse disease models, gene therapy with LAV-BPIFF4 has already been shown to prevent the onset of atherosclerosis, vascular aging, diabetic complications, and rejuvenate the immune system. », he says. He concludes that: there isToday, there is further confirmation and expansion of the therapeutic potential of LAV-BPIFF4. Currently, in vivo studies are being conducted using the recombinant protein in the hearts of the elderly, diabetics, and in the fight against atherosclerosis (characterized by the accumulation of fatty deposits (atherosclerotic plaque) in the arteries). We hope to soon be able to test its effectiveness in clinical trials in patients with heart failure. »