New in Longevity Studies: Centenarian Genes Shown to Rewind Heart Age by 10 Years

Researched and Co-Authored by Shivani Mishra

In a groundbreaking study published in the journal Cardiovascular Research, researchers found that centenarians could be used to help those with heart failure. Associated with exceptional longevity, carriers of healthy mutant genes, like those living in the blue zones of the planet, can protect cells collected from patients with heart failure requiring cardiac transplantation.  

Centenarians usually pass their healthy genes to their offspring, however, this study demonstrates that a healthy gene found in centenarians could be transferred to unrelated people to protect their hearts. In the future scientists may find other mutations with similar or even superior curative potential than the one investigated by this research.

Building on the discovery of the longevity-associated gene variant known as BPIFB4 in 2018, the researchers conducted experiments on human cells in test tubes and later on mice to see if the genes were still able to turn back the biological clock when introduced in a lab instead of being inherited. Funded by the British Heart Foundation, the study found that a single administration of the mutant anti-aging gene halted the decay of heart function in middle aged mice. Additionally, when given to elderly mice - whose hearts exhibit the same alterations observed in elderly patients - it was found that the gene rewound the heart’s biological age by the human equivalent of over 10 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 Bristol based team, led by Professor Madeddu, Professor of Experimental Cardiovascular Medicine from Bristol Heart Institute at the University of Bristol and one of the study’s authors, explained: "The heart and blood vessel function is put at stake as we age. However, the rate at which these harmful changes occur is different among people. Smoking, alcohol, and sedentary life make the ageing clock faster. Whereas eating well and exercising delay the heart’s ageing clock.

"In addition, having good genes inherited from parents can help to stay young and healthy. Genes are sequences of letters that encode proteins. By chance, some of these letters can mutate. Most of these mutations are insignificant; 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."

Monica Cattaneo, a researcher of the MultiMedica Group in Milan, Italy, and first author of the work, said: "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."

Professor Madeddu added: "Our findings confirm the healthy mutant gene can reverse the decline of heart performance in older people. 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. 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.’’

The researchers also found that those same cells seemed to have reduced expression of BPIFB4 as well. In other words, people who tend to develop heart problems may actually be missing this key longevity protein. As University of Bristol professor and co-author Paolo Madedu notes, these findings suggest that introducing a protein to the cells of patients with heart problems may be an alternative to gene therapy, which, in spite of being a promising branch of medical treatment, still carries a number of associated risks.

"Our findings confirm the healthy mutant gene can reverse the decline of heart performance in older people," Madedu said in the press release. "We are now interested in determining if giving the protein instead of the gene can also work."

Like any treatment of this kind, potential treatment will take many years to perfect — regardless, this could be a huge breakthrough and win in the war against heart disease.