Age catches up with us all eventually, but in some people the right genes can make that chase into our twilight years a relatively leisurely one.
A few years ago Italian researchers discovered something special about people who live well into their 90s and beyond: they commonly have a version of a gene called BPIFB4 that protects against cardiovascular damage and keeps the heart in good shape for a longer period of time.
By introducing the mutated gene into older mice, the scientists have now seen how the variant rewinds markers of biological heart aging by the equivalent of more than 10 human years.
In middle-aged mice, the same therapy was shown to halt the decline of heart function.
How quickly the heart and its nearest blood vessels typically decay depends on numerous factors, including how much we drink and whether or not we smoke. Based on the study’s results, mutations in protein-encoding genes also have a key part to play.
The longevity-associated variant (LAV) of the BPIFB4 gene that the researchers looked at is already associated with longevity in people, and is frequently found in individuals who live longer than normal, including those in their late 90s and beyond. This finding prompted the researchers to take a closer look at the variant’s physiological effects.
As well as the tests on mice, the team added the gene to human heart cells in a laboratory setting to see what the effects would be. The cells had been taken from 24 elderly patients with severe heart problems, including some who had previously experienced heart transplants.
The results suggested that LAV-BPIFB4 plays a significant role in maintaining pericyte cells. The job of these cells includes building new blood vessels and keeping them well-maintained, which in turn keeps the heart functioning well for longer.
“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,” says Monica Cattaneo, a cardiovascular researcher from the IRCCS Multimedica Group in Italy and lead author of the study.
“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.”
While centenarians will naturally pass on the BPIFB4 gene mutation to their kids, the thinking is that this could be adapted as a therapy for people whose parents haven’t lived to a grand old age, and who are experiencing heart issues.
Transferring the BPIFB4 gene into mice has already been shown to stop atherosclerosis, diabetes, and other complications, and in the future, clinical trials could be used to see if the same sort of preventative effects happen in humans too.
The researchers are also exploring the possibility of applying the BPIFB4 protein as a treatment, rather than the BPIFB4 gene that generates it. While both options are possible, applying proteins is safer and more straightforward.
“Our findings confirm the healthy mutant gene can reverse the decline of heart performance in older people,” says Madeddu. “We are now interested in determining if giving the protein instead of the gene can also work.”
The research has been published in Cardiovascular Research.