Overview: Researchers say a gene found in many centenarians could reverse the biological age of the heart by ten years. The findings provide a potential target for heart failure patients.
Source: University of Bristol
An anti-aging gene discovered in a population of centenarians has been shown to reverse the biological age of the heart by 10 years.
The breakthrough, published in Cardiovascular examination and led by scientists from the University of Bristol and the MultiMedica Group in Italy, offers a potential target for heart failure patients.
Associated with exceptional longevity, carriers of healthy mutant genes, such as those living in the blue zones of the planet, often live to live 100 years or more and remain in good health. These individuals are also less prone to cardiovascular complications.
Scientists, funded by the British Heart Foundation, believe the gene helps keep their hearts young by protecting them from diseases related to aging, such as heart failure.
In this new study, researchers show that one of these healthy mutant genes, previously found to be particularly frequent in centenarians, can protect cells collected from heart failure patients who need a heart transplant.
The Bristol team, led by Professor Paolo Madeddu, has found that a single administration of the mutated anti-aging gene stopped the decline of heart function in middle-aged mice.
Even more remarkable, when administered to older mice, whose hearts show the same changes as older patients, the gene rewinds the heart’s biological clock by the human equivalent of more than a decade.
Professor Madeddu, Professor of Experimental Cardiovascular Medicine at the Bristol Heart Institute at the University of Bristol and one of the study’s 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 varies from person to person. Smoking, alcohol and a sedentary lifestyle speed up the aging clock. While eating right and exercising slow down the heart’s aging clock.
“In addition, having good genes inherited from parents can help to stay young and healthy. Genes are sequences of letters that code for proteins. Coincidentally, some of these letters can mutate. Most of these mutations are insignificant; in some cases, however, the mutation can make the gene function worse or better, such as for the mutated anti-aging gene that we studied here on human cells and older mice.”
The three-year study was also conducted in human heart cells in a test tube in Italy. Researchers at the MultiMedica Group in Milan, led by Professor Annibale Puca, injected the gene into heart cells from elderly patients with serious heart problems, including transplants, 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 work said: “The cells of the older patients, particularly those that support the construction of new blood vessels called ‘pericytes’, appeared to perform less and getting older.
“By adding the longevity gene/protein to the test tube, we saw a process of heart rejuvenation: the heart cells of older heart failure patients function properly again, which appears to be more efficient at building new blood vessels.”
Centenarians pass on their healthy genes to their offspring. The study shows for the first time that a healthy gene found in centenarians can be passed on to unrelated people to protect their hearts.
In the future, other mutations may be found with similar or even superior curative potential to the one investigated in this study. Professor Madeddu and Professor Annibale Puca of the MultiMedica Group in Milan believe this study could spark a new wave of treatments inspired by the genetics of centenarians.
Professor Madeddu added: “Our findings confirm that the healthy mutant gene can reverse the decline in heart performance in older people. We are now interested in determining whether giving the protein instead of the gene could also work. widely used to treat diseases caused by bad genes, however, protein-based treatment is safer and more viable than gene therapy.
“We have received funding from the Medical Research Council to test healthy gene therapy in Progeria. Also known as Hutchinson-Gilford syndrome, this genetic disease causes premature 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 elderly and diabetic mice, respectively.”
Annibale Puca, head of the laboratory of the IRCCS MultiMedica and professor at the University of Salerno, added: “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 enhancement of the therapeutic potential of the gene/protein. We hope to soon test its effectiveness in clinical trials in patients with heart failure.”
Professor James Leiper, Associate Medical Director at the British Heart Foundation, who funded the research, said: “We all want to know the secrets of aging and how to slow down age-related diseases. Our heart function declines with age, but this research has revealed extraordinary that a variant of a gene commonly found in long-lived humans could halt and even reverse heart aging in mice.
“This is still early stage research, but could one day be a revolutionary way to treat people with heart failure and even prevent the debilitating condition from developing in the first place.”
financing: The study is funded by the British Heart Foundation and the Italian Ministry of Health.
About this news about genetics and heart disease research
Writer: Joanne Fryer
Source: University of Bristol
Contact: Joanne Fryer – University of Bristol
Image: The image is in the public domain
Original research: Open access.
“The longevity-associated BPIFB4 gene supports cardiac function and vascularization in cardiomyopathy of aging” by Paolo Madeddu et al. Cardiovascular examination
Longevity-associated BPIFB4 gene supports cardiac function and vascularization in aging cardiomyopathy
The aging heart is naturally accompanied by a progressive decline in function and perfusion that the available treatments cannot stop. However, some exceptional individuals maintain good health into the very late stages of life due to a favorable gene-environment interaction. We have previously shown that carriers of a longevity-associated variant (LAV) of the BPIFB4 gene enjoy longer health spans and fewer cardiovascular complications. In addition, supplementation of LAV-BPIFB4 via an adeno-associated viral vector improves cardiovascular performance in limb ischemia, atherosclerosis and diabetes models. Here we asked if the LAV-BPIFB4 gene could fill the unmet therapeutic need to slow the spontaneous aging of the heart.
Methods and results
Immunohistological studies showed a marked reduction in pericyte vascular coverage in failing hearts explanted from elderly patients. This defect was attenuated in homozygous carrying patients LAV-BPIFB4 genotype. In addition, pericytes isolated from aged hearts showed low levels of BPIFB4, reduced pro-angiogenic activity and loss of ribosome biogenesis. LAV-BPIFB4 supplementation restored pericyte function and pericyte-endothelial cell interactions through a mechanism involving the nucleolar protein nucleolin. Other way around, BPIFB4 silencing in normal pericytes mimicked the heart failure pericytes. Finally gene therapy with LAV-BPIFB4 prevented cardiac deterioration in middle-aged mice and rescued cardiac function and myocardial perfusion in elderly mice by improving microvasculature density and pericyte coverage.
We report the success of the LAV-BPIFB4 gene/protein in improving homeostatic processes in cardiac aging. These findings open to the use of LAV-BPIFB4 to reverse the decline in cardiac performance in older people.