Researchers studying the hearts of healthy people over the age of 100 have identified specific genetic mutations that appear to play an important role in maintaining cardiovascular function in old age. Through a series of laboratory and animal studies, researchers have demonstrated how a new form of gene therapy can rejuvenate the aging heart.
For over 15 years, a team of Italian researchers has studied the cardiovascular profile of abnormally healthy people over the age of 100. These “very old” are people living past 100 who have a lower incidence of heart disease than the average her 70 or 80.
A breakthrough discovery in 2018 revealed that many heart-healthy super-agers carry specific and unique genetic mutations. In a gene called BPIFB4, longevity-associated variants (LAVs) were found to be associated with significantly reduced incidence of cardiovascular disease. Subsequent animal studies revealed that delivering the gene to mice exerted a protective effect in a model of heart disease.
In this new study, the research team continued to explore the potential therapeutic benefits of this new gene, first in a laboratory test using human heart cells and then in an aged animal model. Monica Cattaneo, lead author of Physiotherapy, said the first lab experiments showed that gene therapy offers great potential for rejuvenating old heart cells.
“We found that the cells in older patients, especially those called ‘pericytes,’ which support the building of new blood vessels, were declining and aging,” explains Cattaneo. “By adding longevity genes/proteins to the test tube, we observed the process of heart rejuvenation. Proven.”
In addition to this finding, the researchers also showed that older people with heart problems often have reduced expression of BPIFB4 in cardiomyocytes and endothelial cells. suggests that this general age-related decline in cardiovascular cells can be prevented.
But perhaps the most compelling finding in the new study was how gene therapy delivering LAV-BPIFB4 to aged mice actually reverses some signs of cardiac aging.
“Recent studies in which LAV-BPIFB4 was administered to 18-month-old mice confirmed improvements in systolic function and coronary flow reserve, which were restored to levels recorded in middle-aged mice,” said the researchers. writing. new research. “Translated to human conditions, the restoration of the contractile index seen in aged mice corresponds to unwinding the cardiac biological clock by more than a decade.”
James Leiper, Associate Medical Director of the British Heart Foundation, pointed out the surprising implications of these new findings. Leiper, who is not working on new research, said these findings could pave the way for treatments to reverse heart aging in older adults.
“Our heart function declines with age, but this study is highly suggestive that mutations in genes commonly found in long-lived people can halt and even reverse cardiac aging in mice.” “While this is still early stage research, it may one day provide an innovative way to treat people with heart failure and even stop the onset of the debilitating condition in the first place.” ”
Dr Paolo Madedu of the University of Bristol was careful not to overstate the findings, suggesting that much work remains to be done before new types of cardiac therapy are used in the clinic. Some of the next steps in research are investigating whether administration of BPIFB4 protein directly improves heart health in mice and moving to early-stage trials in humans.
“Our findings confirm that a healthy mutant gene can reverse the decline in heart function in the elderly,” said Madedu. Gene therapy is widely used to treat diseases caused by bad genes, but protein-based therapy is more effective than gene therapy. It’s safe and viable.”
The study was published in a journal cardiovascular research.
Source: University of Bristol
