Summary: According to researchers, a single gene found in several hundred years can change the biological age of the heart by ten years. The findings suggest potential targets for patients with heart failure.
Source: University of Bristol
An anti-aging gene found in centenarians has been shown to restore heart function by 10 years.
The findings, published in Cardiovascular research And led by scientists at the University of Bristol and Italy’s Multimedica Group, it makes a potential target for patients with heart failure.
Carriers of healthy genetic variants associated with exceptional longevity, such as the planet’s blue zones, often live to be 100 years or more and remain in good health. These people have fewer cardiovascular complications.
Funded by the British Heart Foundation, the scientists believe the gene could help keep the heart young by preventing age-related diseases such as heart failure.
In this new study, researchers have shown that one of these healthy mutations in the gene can protect cells collected from patients with heart failure after a heart transplant, which has already been confirmed in hundreds of people.
The Bristol team, led by Professor Paolo Madedu, found that a single administration of a mutant anti-aging gene halted the deterioration of heart function in middle-aged mice.
Amazingly, when given to old mice whose hearts show similar changes to those of elderly patients, the gene restores the heart’s biological clock by more than a decade in humans.
Professor Madeu, Professor of Experimental Cardiovascular Medicine at the Bristol Heart Institute at the University of Bristol and one of the study’s authors, explained: “Cardiovascular function is compromised as we age.
“However, the rate at which these harmful changes occur varies between people. Smoking, alcohol and a sedentary lifestyle speed up the aging clock. Eating well and exercising can delay the aging clock of the heart.
“Also, having good genes inherited from parents helps to stay young and healthy. Genes are sequences of letters that code for proteins. Incidentally, some of these letters can mutate. Most of these mutations are insignificant; In some cases, however, a mutation can make a gene function worse or better; For example, a mutated anti-aging gene that we studied here in human cells and aged mice.
The three-year study was conducted in test tubes of human heart cells in Italy. Researchers at the Multimedica Group in Milan, led by Professor Anibal Puca, analyzed the gene expression of heart cells from elderly patients with severe heart disease, including transplants, and then compared their function to healthy people.
Monica Cattaneo, a researcher at the Multimedica Group in Milan, Italy and the first author of the work, said: “Cells from elderly patients, specifically cells called ‘pericytes’, were found to support the formation of new blood vessels. Less performance and more aging.
“By adding a longevity gene/protein in a test tube, we observed a process of cardiac regeneration: heart cells in elderly heart failure patients continued to function properly and became more efficient at building new blood vessels.”
Centenarians pass on their healthy genes to their children. The study has shown for the first time that healthy genes can be transferred to unrelated people to protect their hearts.
Other mutations with similar or greater therapeutic potential than those investigated in this study may be discovered in the future. Professor Madedu and Professor Anibal Puca of the Multimedica Group in Milan believe that this study could lead to a new wave of treatments that could lead to hundreds of people being genetically motivated.
Professor Madedu added: “Our findings confirm that the healthy mutation gene can reverse the decline in cardiac performance in the elderly.” Now we are interested in whether giving a protein instead of a gene might work. Gene therapy is widely used to treat diseases caused by bad genes. However, protein-based therapy is safer and more cost-effective than gene therapy.
We have received funding from the Medical Research Council to trial healthy gene therapy in progeria. This genetic disease, also known as Hutchinson-Gilford syndrome, causes damage to children’s hearts and arteries as they get older. We were also funded by the British Heart Foundation and Diabetes UK to investigate aged mice and diabetic mice, respectively.
Anibal Puca, head of the laboratory at IRCCS Multimedica and professor at the University of Salerno, added: “Gene therapy with the healthy gene has already been shown to prevent atherosclerosis, vascular aging and diabetes complications in disease models.” , and to restore the immune system.
“We have new validation and expansion 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 of the British Heart Foundation, which funded the research, said: “We all want to know the mysteries of aging and how we can reduce age-related diseases. Our heart’s function declines with age, but this study found that a gene variant found in unusually long-lived people can stop and even reverse the aging of the heart in mice.
“This is still preliminary research, but one day it could provide a revolutionary way to treat people with heart failure and even prevent the condition from developing in the first place.”
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Financial support The study was funded by the British Heart Foundation and the Italian Ministry of Health.
So genetics and heart disease research news
Author: Joan Fryer
Source: University of Bristol
Contact: Joan Fryer – University of Bristol
Image: The image is in the public domain.
Preliminary study: Open Access.
“The longevity-associated BPIFB4 gene supports cardiac function and cardiacization in aging cardiomyopathy.” by Paolo Madedu et al Cardiovascular research
Draft
The longevity-associated BPIFB4 gene supports cardiac function and cardiacization in aging cardiomyopathy.
Objectives
The aging heart naturally causes a progressive decrease in activity and blood flow, which existing treatments cannot stop. However, some exceptional individuals maintain good health until late in life due to gene-environment interactions. We have previously shown that carriers of the variant are associated with longevity (LAV) of the BPIFB4 Genes enjoy long-term health and fewer cardiovascular problems. Moreover, the complement of via LAV-BPIFB4 Adeno-linked viral vector improves cardiovascular performance in models of limb ischemia, atherosclerosis, and diabetes. Here, we asked if. LAV-BPIFB4 Gene may address an unmet medical need to slow the premature aging of the heart.
Methods and results
Immunohistological studies showed a remarkable reduction in the pericyte vessel layer in the hearts of elderly patients. This defect is weakened in patients carrying homozygosity LAV-BPIFB4 Genotyping Furthermore, pericytes isolated from old hearts showed low levels of BPIFB4, depressed pro-angiogenic activity and loss of ribosome biogenesis. LAV-BPIFB4 Additional pericyte function and pericyte-endothelial cell interactions are restored through a mechanism involving the nucleolar protein nucleolin. On the contrary, BPIFB4 Silence in normal pericytes mimicked heart failure pericytes. Finally, gene therapy LAV-BPIFB4 Prevention of cardiac degeneration in middle-aged mice and improvement of microvascular density and pericyte coverage by improving cardiac function and heart rate in old mice.
Conclusions
We report the success of the LAV-BPIFB4 gene/protein in improving homeostatic processes in the aging heart. These findings open the door to the use of LAV-BPIFB4 to reverse cardiac performance decline in the elderly.