Heart diagram

[Medical Illustrations by Patrick Lynch, generated for multimedia teaching projects by the Yale University School of Medicine, Center for Advanced Instructional Media, 1987-2000. Via WikiMedia Commons]

A recently published paper in Cardiovascular Research found that a gene frequently found in centenarians could safeguard heart functionality.

In a rodent model, a team of researchers found that the bactericidal/permeability-increasing fold-containing family-B member-4 gene (BPIFB4) gene protected against deterioration of heart function in middle-aged mice (14 months old).

The researchers, led by Professor Paolo Madeddu of the University of Bristol, found that delivery of the gene through an adeno-associated virus (AAV serotype 9) with a liver-specific promoter led to robust protection against cardiovascular disease in rodents.

The study focused on the cardiac index and vascular density.

The BPIFB4 gene, when administered to elderly mice (18 months old), reversed the decrease of heart performance by the equivalent of 10 years in humans.

The researchers found that older failing hearts were deficient in the BPIFB4 protein and had a corresponding scarcity in capillaries and surrounding pericytes, cells found along the walls of capillaries.

“Most [genetic] mutations are insignificant,” Madeddu said in a press release. “In a few cases, however, the mutation can make the gene function worse or better, like for the mutant anti-aging gene we have studied here on human cells and older mice.”

The researchers noted that long-lived individuals are more likely to carry the longevity-associated variant of the BPIFB4 gene, which expresses high levels of the BPIFB4 protein in the blood. In addition, the protein may have anti-inflammatory properties.

The researchers also tested the BPIFB4 gene in an in vitro study involving human cardiac cells.

“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,” said Monica Cattaneo, a researcher of the MultiMedica Group in Milan, Italy, in a press release.

The BPIFB4 protein protects heart function and appears to also play a role in the immune response, helping clear bacteria and other pathogens from the bloodstream.

In 2020, a research paper published in the International Journal of Molecular Sciences concluded that BPIFB4 could help treat hypertension, atherosclerosis, diabetic cardiopathy and other conditions.

A 2019 paper published in European Heart Journal projected that the same gene could protect against chronic ischemia.