Science

A special gene found in centenarians rejuvenates the heart by more than 10 years

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In some regions of the world, called “blue zones”, the number of centenarians and “supercentenarians” is unusually large. Many studies are trying to unravel the secret of their longevity, in order to possibly develop anti-aging therapy. Based on genetics, a new study has identified a “mutated anti-aging gene” particularly common in long-lived people living in the blue zones. Implanted in mice with heart failure, the gene would push back the biological age of their hearts by 10 years (by transferring the effect to the time scale of the human heart). In what is undoubtedly a major breakthrough, the famous gene allowed slowing down the degradation of animal heart cells, as well as human heart cells isolated in the context of another trial.

In many Western countries where health care systems are strong, reaching the age of 80-90 is no longer uncommon. However, exceeding 100 years is still a feat, except in a few regions of the world. In these so-called Blue Zones, people are much more likely to reach their 100th birthday while remaining in good health.

The two most famous blue zones are in Sardinia (Italy), in several small mountain villages and on the island of Okinawa (in Japan). In particular, there is the highest density in the world of centenarians and ninety-year-olds in excellent shape, despite their advanced age. Past research has identified other regions, bringing the total number of blue zones to five today, adding: Loma Linda (in California), Ikaria Island (in Greece) and the Nicoya Peninsula (in Costa Rica).

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Previous research has shown that the secret to the longevity of these populations is partly due to their lifestyle. Although the habitats are very far from each other, nevertheless, they have common features in their lifestyle and living conditions. The first common point is that all these people live in sunny and well-ventilated areas, often located at a height.

Despite their differences, their diets usually include plenty of fruits and vegetables. Meat, fish or cheese is eaten in moderation or only on holidays. Some even practice voluntary calorie restriction. The consumption of alcohol, especially wine, is also reduced. As for physical activity, it is naturally practiced regularly, since it is associated with field and livestock work. There was also a low level of stress, in particular due to a simple life and closeness to nature, strong social and family ties, deep spiritual aspirations, etc.

Biologically centenarians living in these areas will also be endowed with “longevity genes”. Since the contribution of the genome to life expectancy is about 25%, scientists decided that genetics would be one of the best ways to study the secret of longevity. With this study in mind, a team from the University of Bristol (UK) and the MultiMedica group (Italy) identified a healthy mutant gene (which mutated to provide health benefits) that is partly responsible for the longevity of centenarians.

“A mutation can make a gene work worse or better, like the mutant anti-aging gene we studied here in human cells and old mice,” says Paolo Madeddu, professor of experimental cardiovascular medicine at Bristol and co-author of the new study. study published in the journal Cardiovassal Research. The gene, called LAV-BPIFB4, is thought to be a variant associated with longevity and confer long-term health along with reduced age-related cardiovascular disease.

The new study aims to understand how to apply the effects of this gene to patients suffering from heart failure. This gene, which is especially common in centenarians, is said to have the ability to protect and restore the function of heart cells in patients suffering from this disease. This will be the first study to show that a longevity gene found in centenarians can be implanted into other people’s cells without the need for a family connection.

The gene that reverses the decline in heart rate

Based on trials spanning almost three years, researchers in a new study implanted the infamous gene into heart cells taken from elderly patients with serious cardiovascular problems. These cells were then compared with heart cells from healthy people to evaluate the effect of the gene.

The research team was able to observe that the patients’ heart cells regained their functions, in particular, became more efficient in pumping blood. In particular, rejuvenation processes were observed at the level of pericytes, cells that support the restoration of damaged blood vessels.

In addition, the researchers also implanted the gene into middle-aged mice, in which they previously caused the same cardiac changes seen in older patients. Result: The gene slowed the deterioration of their heart function. Even more strikingly, their hearts would look younger by an average of more than 10 years (by transferring the effect to the time scale of the human heart). This rejuvenation would have the effect of preventing the onset of atherosclerosis, aging of the vascular and immune systems, and complications associated with diabetes.

“Our results confirm that a healthy mutant gene can reverse cardiac decline in older people,” Madeddu notes. To continue their research, the scientists will try to determine whether a protein (which encodes a gene) can be used instead of a gene. According to experts, treatment based on this protein will be more viable and safer than gene therapy. In addition, the researchers plan to test the effect of the gene on the heart cells of children with progeria (a genetic disease that causes abnormally accelerated aging).

Cardiovascular Research.

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