Anti-aging gene shown to set back heart age by 10 years

Anti-aging gene shown to set back heart age by 10 years
Anti-aging gene shown to set back heart age by 10 years

Summary: Researchers say a gene found in many centenarians can reverse the biological age of the heart by ten years. The results offer a potential target for patients with heart failure.

Source: University of Bristol

An anti-aging gene discovered in a population of centenarians has been shown to delay the biological age of the heart by 10 years.

The breakthrough, published in Cardiovascular research and led by scientists from the University of Bristol and the MultiMedica Group in Italy, offers a potential target for patients with heart failure.

Associated with exceptional longevity, carriers of healthy mutant genes, such as those living in the blue zones of the planet, often live to be 100 years or more and remain healthy. These people are also less prone to cardiovascular complications.

Scientists funded by the British Heart Foundation believe the gene helps keep their hearts young by protecting against age-related diseases, such as heart failure.

In this new study, the researchers demonstrate that one of these healthy mutant genes, previously shown to be particularly common in centenarians, can protect cells taken from heart failure patients requiring heart transplantation.

The Bristol team, led by Professor Paolo Madeddu, found that a single administration of the mutant anti-aging gene halted the deterioration of heart function in middle-aged mice.

Even more remarkably, when given to aged mice, whose hearts show the same alterations seen in elderly patients, the gene rewound the age of the heart’s biological clock by the human equivalent by more than ten years.

Professor Madeddu, Professor of Experimental Cardiovascular Medicine at Bristol Heart Institute, University of Bristol and one of the study’s authors, explained: “The function of the heart and blood vessels comes into play with age. .

“However, the speed at which these harmful changes occur is different in different people. Smoking, alcohol and physical inactivity accelerate aging. While eating well and exercising delays the heart’s aging clock.

“Plus, having good genes inherited from parents can help keep you young and healthy. Genes are sequences of letters that code for proteins. Luckily, some of these letters can mutate. Most of these mutations are insignificant; in a few cases, however, the mutation can make the gene work worse or better, such as the mutant anti-aging gene we studied here in human cells and older mice.

The three-year study was also carried out in human heart cell test tubes in Italy. Researchers from the MultiMedica group in Milan, led by Professor Annibale Puca, administered the gene into heart cells of elderly patients with serious heart problems, including transplantation, and then compared their function with those of healthy individuals. .

Monica Cattaneo, researcher at MultiMedica Group in Milan, Italy, and first author of the work, said: “Cells from elderly patients, particularly those that support the construction of new blood vessels, called ‘pericytes’, have been shown to be less efficient and older.

“By adding the longevity gene/protein to the test tube, we observed a process of cardiac rejuvenation: heart cells from elderly patients with heart failure began to function properly again, proving to be more efficient at building new vessels blood.

Centenarians pass on their healthy genes to their offspring. The study demonstrates for the first time that a healthy gene found in centenarians could be transferred to unrelated people to protect their hearts.

Other mutations may be found in the future with similar or even greater healing potential than that investigated by this research. Professor Madeddu and Professor Annibale Puca of the MultiMedica group in Milan think the study could fuel a new wave of treatments inspired by the genetics of centenarians.

Professor Madeddu added: “Our findings confirm that the healthy mutant gene can reverse cardiac performance decline in the elderly. We now want to see if giving the protein instead of the gene might also work. Gene therapy is widely used to treat diseases caused by bad genes. However, protein-based treatment is safer and more viable than gene therapy.

In this new study, the researchers demonstrate that one of these healthy mutant genes, previously shown to be particularly common in centenarians, can protect cells taken from heart failure patients requiring heart transplantation. Image is in public domain

“We have received funding from the Medical Research Council to test a healthy gene therapy in Progeria. This genetic condition, also known as Hutchinson-Gilford syndrome, causes early damage to the heart and blood vessels of children. We were also funded by the British Heart Foundation and Diabetes UK to test the protein in elderly and diabetic mice, respectively.

Annibale Puca, head of the IRCCS MultiMedica laboratory and professor at the University of Salerno, added: “Gene therapy with the healthy gene has already been shown in mouse disease models to prevent the onset of atherosclerosis, vascular aging and diabetes complications. , and to rejuvenate the immune system.

“We have further confirmation and expansion of the therapeutic potential of the gene/protein. We hope to test its effectiveness soon in clinical trials on patients with heart failure.

Professor James Leiper, Associate Medical Director at the British Heart Foundation, which funded the research, said: “We all want to know the secrets of aging and how we could slow down age-related disease. Our heart function declines with age, but this research has amazingly revealed that a variant of a gene commonly found in long-lived people can halt and even reverse heart aging in mice.

“This is still early-stage research, but it could one day provide a revolutionary way to treat people with heart failure and even prevent the debilitating disease from developing in the first place.”

Funding: The study is funded by the British Heart Foundation and the Italian Ministry of Health.

About this genetics and heart disease research news

Author: Joanne Fryer
Source: University of Bristol
Contact: Joanne Fryer – University of Bristol
Picture: Image is in public domain

Original research: Free access.
“The longevity-associated BPIFB4 gene supports cardiac function and vascularization in aging cardiomyopathy” by Paolo Madeddu et al. Cardiovascular research


Summary

Longevity-associated BPIFB4 gene supports cardiac function and vascularization in aging cardiomyopathy

Goals

The aging heart naturally experiences a gradual decline in function and perfusion that available treatments cannot reverse. However, some exceptional individuals remain healthy until very late in life thanks to a favorable gene-environment interaction. We have previously shown that carriers of a variant associated with longevity (LAV) of BPIFB4 gene benefit from prolonged health and fewer cardiovascular complications. In addition, supplementation with LAV-BPIFB4 via an adeno-associated viral vector improves cardiovascular performance in models of limb ischemia, atherosclerosis and diabetes. Here we asked if the LAV-BPIFB4 may address the unmet therapeutic need to delay spontaneous heart aging.

Methods and results

Immunohistological studies have shown a remarkable reduction in vascular coverage by pericytes in failing hearts explanted from elderly patients. This defect was attenuated in patients carrying the homozygote LAV-BPIFB4 genotype. Additionally, pericytes isolated from older 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. Conversely, BPIFB4 silence in normal pericytes mimicked heart failure pericytes. Finally, gene therapy with LAV-BPIFB4 prevented cardiac deterioration in middle-aged mice and rescued cardiac function and myocardial perfusion in older mice by improving microvasculature density and pericyte coverage.

conclusion

We report the success of the LAV-BPIFB4 gene/protein in improving homeostatic processes in the aging heart. These results pave the way for the use of LAV-BPIFB4 to reverse cardiac performance decline in the elderly.

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