Scientists discover anti-aging gene that rewinds heart age by 10 years
A single administration of the mutant anti-aging gene stopped the decay of heart function in middle-aged mice.
Researchers at the University of Bristol and the MultiMedica Group in Italy discovered a certain gene in a population of centenarians that has helped keep their hearts young by protecting them against diseases linked to aging, such as heart failure.
This anti-aging gene was found in a group of people living in the blue zones of the planet. Blue zones are regions in the world where people are speculated to live longer than average. They include Okinawa, Japan; Sardinia, Italy; Nicoya, Costa Rica; Icaria, Greece; and Loma Linda, California, United States.
Individuals in these zones often live up to 100 years or more and remain in good health. They’re also less prone to cardiovascular complications. In this study, researchers demonstrated that one of these healthy mutant genes proved to be frequent in centenarians and can protect cells collected from patients with heart failure requiring cardiac transplantation, as per a release.
The anti-aging gene stopped the decay of heart function
The Bristol team, led by Professor Paolo Madeddu, found that a single administration of the mutant anti-aging gene stopped the decay of heart function in middle-aged mice. And when administered to elderly mice, the gene rewound the heart’s biological clock age by the human equivalent of more than ten years.
The three-year study was also performed in test tube human cardiac cells in Italy. Researchers from the MultiMedica Group in Milan led by Professor Annibale Puca administered the gene in heart cells from elderly patients with severe heart problems, including transplantation, and then compared their function with those of healthy individuals.
“The cells of the elderly patients, in particular those that support the construction of new blood vessels, called ‘pericytes,’ were found to be less performing and more aged. By adding the longevity gene/protein to the test tube, we observed a process of cardiac rejuvenation: the cardiac cells of elderly heart failure patients have resumed functioning properly, proving to be more efficient in building new blood vessels,” Monica Cattaneo, a researcher of the MultiMedica Group in Milan, Italy, and first author of the work, said in a statement.
It is a known fact that centenarians pass their healthy genes to their offspring. For the first time, this study demonstrates that a healthy gene found in centenarians could be transferred to unrelated people to protect their hearts.
A new wave of treatments inspired by the genetics of the centenarians
The researchers firmly believe that the study may “fuel a new wave of treatments inspired by the genetics of centenarians.”
“Our findings confirm the healthy mutant gene can reverse the decline of heart performance in older people. We are now interested in determining if giving the protein instead of the gene can also work. Gene therapy is widely used to treat diseases caused by bad genes. However, a treatment based on a protein is safer and more viable than gene therapy,” said Professor Madeddu.
“We have a new confirmation and enlargement of the therapeutic potential of the gene/protein. We hope to test its effectiveness soon in clinical trials on patients with heart failure,” added Puca, Head of the laboratory at the IRCCS MultiMedica and Professor at the University of Salerno.
The study is published in Cardiovascular Research.
Study Abstract:
The aging heart naturally incurs a progressive decline in function and perfusion that available treatments cannot halt. However, some exceptional individuals maintain good health until the very late stage of their life due to favorable gene-environment interaction. We have previously shown that carriers of a longevity-associated variant (LAV) of the BPIFB4 gene enjoy prolonged health spans and lesser cardiovascular complications. Moreover, 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 address the unmet therapeutic need to delay the heart’s spontaneous aging.
Immunohistological studies showed a remarkable reduction in vessel coverage by pericytes in failing hearts explanted from elderly patients. This defect was attenuated in patients carrying the homozygous LAV-BPIFB4 genotype. Moreover, pericytes isolated from older hearts showed low levels of BPIFB4, depressed 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 silencing in normal pericytes mimed 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 older mice by improving microvasculature density and pericyte coverage.
We report the success of the LAV-BPIFB4 gene/protein in improving homeostatic processes in the heart’s aging. These findings open to using LAV-BPIFB4 to reverse the decline of heart performance in older people.
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