Scientists have borrowed a trick from people who live past 100 to tackle one of medicine’s cruelest puzzles: a disease that makes children age at warp speed. In a study that sounds almost like science fiction, researchers injected mice with a “longevity gene” taken from supercentenarians and watched the rodents’ damaged hearts begin to heal.
The disease is Hutchinson-Gilford Progeria Syndrome, or HGPS, and it turns childhood into a race against time. Kids with progeria develop wrinkled skin, lose their hair, and suffer cardiovascular problems that typically kill them before they reach voting age. The culprit is a mutant protein called progerin that warps the nucleus of cells, the command center where DNA lives and genes get their marching orders.
Only one drug has FDA approval for progeria: lonafarnib, which slows progerin buildup but doesn’t stop the damage. A clinical trial launched last October is testing whether pairing lonafarnib with another compound might work better. But what if, instead of just blocking the bad protein, doctors could teach cells to shrug off its effects?
The Supercentenarian Solution
That’s where the longevity gene comes in. Dr. Yan Qiu and Professor Paolo Madeddu at the University of Bristol teamed up with Professor Annibale Puca’s group in Italy to test whether a gene variant found in people who live past 100, called LAV-BPIFB4, could protect progeria patients from progerin’s toxic effects. Previous work had shown this gene helps keep hearts and blood vessels healthy during normal aging, so the researchers wondered if it might do the same trick in progeria, where aging happens on fast-forward.
They engineered mice to have progeria and watched the animals develop heart problems eerily similar to those seen in human children with the disease. By seven or eight months of age, the mice showed signs of diastolic dysfunction, meaning their hearts couldn’t relax and fill with blood properly. It’s the same problem cardiologist Ashwin Prakash and colleagues documented in kids with HGPS, and they suspected scar tissue in the heart muscle was to blame.
Then came the intervention. A single injection of the longevity gene, delivered via a viral vector that homes in on heart tissue, started to turn things around. Two months later, the treated mice showed improved heart function. Specifically, their hearts could relax better and fill more efficiently with blood.
“Our research has identified a protective effect of a supercentenarian longevity gene against progeria heart dysfunction in both animal and cell models. The results offer hope to a new type of therapy for Progeria; one based on the natural biology of healthy aging rather than blocking the faulty protein.”
The gene didn’t just improve how the hearts pumped. When the researchers examined heart tissue under the microscope, they found less scarring around blood vessels and more tiny new vessels sprouting to feed the muscle. They also counted fewer senescent cells, the worn-out cellular zombies that accumulate with age and pump out inflammatory signals.
Protecting Cells Without Removing Poison
To figure out how this protection works, the team turned to human cells from progeria patients. These cells showed lower levels of their own BPIFB4 compared to cells from healthy people, suggesting progerin somehow suppresses the gene. The cells also churned out markers of aging and fibrosis: proteins like collagen, elastin, and a growth factor called epiregulin that’s linked to scarring.
When the researchers added the longevity gene to these sick cells, the markers of aging and fibrosis dropped. But here’s the twist: progerin levels stayed exactly the same. The gene wasn’t removing the poison; it was helping cells cope with it.
That’s a fundamentally different approach from existing treatments. Instead of trying to eliminate progerin, which has proved difficult, the longevity gene seems to shield cells from its worst effects. The mechanism likely involves the cell’s nucleolus, the ribosome factory inside the nucleus where LAV-BPIFB4 is known to interact with RNA-binding proteins. By supporting ribosome assembly and other nucleolar functions that progerin disrupts, the gene may help cells maintain critical operations even in a toxic environment.
“This is the first study to indicate that a longevity-associated gene can counteract the cardiovascular damage caused by progeria. The results pave the way for new treatment strategies for this rare disease, which urgently requires innovative cardiovascular drugs capable of improving both long-term survival and patient quality of life.”
The study, published in Signal Transduction and Targeted Therapy, is the first to show a supercentenarian gene can slow heart aging in a progeria model. It’s a proof of concept that genes from the longest-lived among us might hold keys to treating diseases of accelerated aging, and possibly normal aging too.
The researchers note that gene therapy isn’t the only way to deliver LAV-BPIFB4. Future treatments might use proteins or RNA-based methods instead, potentially making the therapy easier to administer and control. And while progeria affects only about 400 children worldwide at any given time, the lessons learned could apply more broadly to age-related heart disease affecting millions.
The work takes on added poignancy in light of Sammy Basso’s death last October at age 28. Basso was the oldest known person with progeria, a testament to how far some patients can push against the disease with current care. The hope is that treatments like this could give more children with progeria the chance to do the same.
Signal Transduction and Targeted Therapy: 10.1038/s41392-025-02416-3
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