Anti-aging gene shown to reverse heart age by 10 years

Summary: Researchers say a gene found in many centenarians can reverse the heart’s biological age 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 push back the biological age of the heart by 10 years.

The discovery, 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 planet’s blue zones, often live to be 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 that the gene helps keep their hearts young, protecting them against diseases linked to aging, such as heart failure.

In this new study, the researchers demonstrate that one of these healthy mutant genes, previously shown 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, found that a single administration of the mutant anti-aging gene stopped the deterioration of heart function in middle-aged mice.

Even more remarkably, when given to elderly mice, whose hearts exhibit the same changes seen in elderly patients, the gene turned back the heart’s biological clock by a human equivalent of more than ten years.

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 is put at risk as we age.

“However, the rate at which these harmful changes occur differs between people. Smoking, alcohol and a sedentary lifestyle speed up the aging clock. Whereas eating well and exercising slows down the heart’s aging clock.

“Also, having good genes inherited from parents can help you stay young and healthy. Genes are strings of letters that code for proteins. By chance, some of these letters may mutate. Most of these mutations are insignificant; in some cases, however, the mutation can make the gene function worse or better, as in the case of the mutant anti-aging gene that we studied here in human cells and older mice.”

The three-year study was also performed on test-tube human heart cells in Italy. Researchers at the MultiMedica Group in Milan, led by Professor Annibale Puca, administered the gene into heart cells from elderly patients with serious heart problems, including transplantation, and then compared its 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, in particular those that support the construction of new blood vessels, called ‘pericytes’, were to be less performant and more aged. .

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

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

Other mutations may be found in the future with a curative potential similar or even superior to that investigated in this research. Professor Madeddu and Professor Annibale Puca of the MultiMedica Group in Milan believe this 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 the decline in cardiac performance in older people. We are now interested in determining whether giving the protein instead of the gene might also work. Gene therapy is widely used to treat diseases caused by bad genes. However, a 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 frequent in centenarians, can protect cells collected from heart failure patients who need a heart transplant. The image is in the public domain

“We 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. We were also funded by the British Heart Foundation and Diabetes UK to test the protein in older 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 in disease models in mice 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 expansion of the therapeutic potential of the gene/protein. We hope to test its effectiveness soon in clinical trials in 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 can delay age-related diseases. Our heart function declines with age, but this research has remarkably 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 one day it could provide a revolutionary way to treat people with heart failure and even prevent the debilitating condition from developing in the first place.”

See too

It shows a brain

Financing: 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 FryerUniversity of Bristol
Image: The image is in the public domain

Original search: Free access.
“The BPIFB4 gene associated with longevity supports cardiac function and vascularity in aging cardiomyopathy” by Paolo Madeddu et al. cardiovascular research


Summary

Longevity-associated BPIFB4 gene supports heart function and vascularity in aging cardiomyopathy

Aim

The aging heart naturally incurs a progressive decline in function and perfusion that available treatments cannot stop. However, some exceptional individuals maintain good health until later in life due to favorable gene-environment interaction. We have previously shown that carriers of a longevity-associated variant (WASH) of BPIFB4 gene enjoy longer periods of health and less cardiovascular complications. Furthermore, the supplementation of LAV-BPIFB4 via an adeno-associated viral vector improves cardiovascular performance in models of limb ischemia, atherosclerosis and diabetes. Here, we ask whether the LAV-BPIFB4 The gene could address an unmet therapeutic need to slow the heart’s spontaneous aging.

Methods and Results

Immunohistological studies have shown a remarkable reduction in vessel coverage by pericytes in failed hearts explanted from elderly patients. This defect was attenuated in patients carrying the homozygote LAV-BPIFB4 genotype. Furthermore, pericytes isolated from older hearts showed low levels of BPIFB4, depressed proangiogenic activity and loss of ribosomal biogenesis. LAV-BPIFB4 supplementation restored pericyte function and pericyte-endothelial cell interactions through a mechanism involving the nucleolar protein nucleolin. On the other hand, BPIFB4 silencing 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.

Conclusions

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

Anti-aging gene shown to reverse heart age by 10 years

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