A gene that teaches cells to survive, rather than removing the threat
In the quiet persistence of those who have lived past a century, scientists have found an unexpected gift for children whose bodies age far too fast. Researchers at the University of Bristol and IRCCS MultiMedica have identified a longevity gene — LAV-BPIFB4 — drawn from supercentenarians, and shown for the first time that it can shield young hearts from the ravages of progeria, a fatal rapid-aging disease that claims most of its sufferers before adulthood. Rather than fighting the disease's toxic protein directly, this approach asks what the longest-lived among us already know — and borrows their biology as medicine.
- Progeria gives children the hearts of the very old, and most die of cardiac failure in their teens, making every year without a new treatment a year the disease wins.
- Current therapies target the faulty protein progerin itself, but even the best available drug, lonafarnib, only slows the damage — it does not teach the body to endure it.
- A single injection of the centenarian gene LAV-BPIFB4 improved heart relaxation, reduced scarring, cleared aged cells, and sparked new blood vessel growth in progeria mice — without touching progerin levels at all.
- The same protective effects appeared in human progeria cells in the lab, suggesting the gene helps cells cope with toxic stress rather than simply removing its source.
- Scientists are now working to translate this into deliverable gene therapy, exploring RNA- and protein-based methods that could move toward clinical trials.
- The implications reach far beyond progeria — a gene that keeps centenarian hearts resilient may one day slow ordinary age-related heart disease in millions of people.
Scientists at the University of Bristol and IRCCS MultiMedica have made a striking discovery: a gene associated with exceptional human longevity appears capable of protecting children's hearts from progeria, a rare and fatal disease that forces the body to age at a devastating pace. The finding, published in Signal Transduction and Targeted Therapy, is the first demonstration that a longevity gene can slow cardiac aging in progeria models.
Progeria arises from a mutation that produces a toxic protein called progerin, which corrupts the cell's nucleus and triggers premature aging throughout the body. Most children with the condition die of heart failure in their teens. Sammy Basso, the longest-known survivor, died last year at 28. Existing treatments, including the FDA-approved drug lonafarnib, work by reducing progerin buildup — but they remain a partial answer to a relentless disease.
The Bristol and MultiMedica team, led by Dr. Yan Qiu and Professor Paolo Madeddu alongside Professor Annibale Puca's group in Italy, chose a different strategy entirely. They turned to LAV-BPIFB4, a gene found at elevated levels in supercentenarians and previously linked to cardiovascular health in normal aging. When injected into progeria mice, the gene produced remarkable results: improved heart function, less tissue scarring, fewer aged cells, and new blood vessel growth — all from a single dose. Crucially, the same protective effects appeared in human progeria cells, and none of it required lowering progerin levels.
This is what makes the approach genuinely novel. Instead of attacking the faulty protein, the longevity gene appears to help cells endure its effects — drawing on the natural biology of healthy aging rather than fighting disease on its own terms. Dr. Qiu described it as a new type of therapy rooted in how resilient bodies actually work.
The road to clinical use requires solving the delivery problem — how to safely administer the gene to patients — and researchers are exploring RNA- and protein-based methods as alternatives to direct gene therapy. Professor Puca's team is already extending the work to other cardiovascular and immune conditions. The broader promise is significant: if the genetic signatures of the longest-lived humans can protect young hearts racing toward failure, they may also hold clues for slowing the heart disease that quietly burdens millions in ordinary old age.
Researchers at the University of Bristol and IRCCS MultiMedica have identified a gene linked to exceptional longevity in people over 100 years old that appears capable of reversing damage caused by progeria, a rare genetic disease that forces children's bodies to age at an accelerated pace. The discovery, published in Signal Transduction and Targeted Therapy, marks the first time scientists have shown that a longevity gene can slow heart aging in progeria models—a finding that offers a fundamentally different approach to treating a condition that has long seemed intractable.
Progeria, formally known as Hutchinson-Gilford progeria syndrome, stems from a mutation in the LMNA gene that produces a toxic protein called progerin. This protein damages cells by disrupting the nucleus, the cell's control center, triggering premature aging throughout the body. The disease is relentless: most children with progeria die in their teens from heart failure, though a few have lived longer. Sammy Basso, the oldest known person with the condition, died last year at 28. The current FDA-approved treatment, a drug called lonafarnib, can reduce progerin buildup, and researchers are now testing whether combining it with another drug called Progerinin might work better. But these approaches still aim to block or reduce the faulty protein itself.
The Bristol and MultiMedica team took a different path. Led by Dr. Yan Qiu and Professor Paolo Madeddu at Bristol Heart Institute, working with Professor Annibale Puca's group in Italy, they asked whether genes from supercentenarians—people who have lived exceptionally long lives—might protect progeria patients from progerin's damage. They focused on a gene called LAV-BPIFB4, known from previous research to help keep the heart and blood vessels healthy during normal aging.
Using mice genetically engineered to have progeria, the team injected the longevity gene and observed striking results. A single injection improved heart function, particularly the heart's ability to relax and fill with blood—a measure called diastolic function. The treatment reduced scarring in heart tissue, decreased the number of aged cells in the heart, and stimulated growth of new small blood vessels that could nourish heart tissue. The researchers then tested the gene in human cells taken from progeria patients and found similar protective effects: the gene reduced signs of aging and tissue damage without directly lowering progerin levels.
This distinction matters profoundly. Rather than trying to eliminate the toxic protein, the LAV-BPIFB4 gene appears to help cells withstand progerin's effects—a strategy rooted in how healthy bodies naturally manage aging. Dr. Qiu noted that this approach "offers hope to a new type of therapy for progeria; one based on the natural biology of healthy aging rather than blocking the faulty protein." Professor Puca emphasized that the findings "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 path forward involves translating these laboratory results into clinical reality. Researchers are exploring how to deliver the LAV-BPIFB4 gene through gene therapy, and considering whether protein- or RNA-based delivery methods might eventually replace or complement direct gene administration. Puca's team is already conducting multiple studies to investigate whether this longevity gene might protect the cardiovascular and immune systems in other disease conditions. The implications extend beyond progeria: if a gene that enables people to live past 100 can protect young hearts from rapid aging, it might also offer insights into slowing age-related heart disease in the general population—a condition that affects millions. The research suggests that the secrets of longevity, written in the genes of the longest-lived people, may hold answers for those whose bodies are racing against time.
Citas Notables
This approach offers hope to a new type of therapy for progeria based on the natural biology of healthy aging rather than blocking the faulty protein.— Dr. Yan Qiu, Bristol Heart Institute
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.— Professor Annibale Puca, IRCCS MultiMedica
La Conversación del Hearth Otra perspectiva de la historia
Why does a gene from people who live past 100 help children whose bodies are aging too fast?
Because the gene doesn't fight aging itself—it teaches cells how to stay healthy despite damage. Supercentenarians have figured out how to live long, and their genes reflect that wisdom. We're borrowing it.
So you're not curing progeria, you're making the body more resilient to it?
Exactly. The toxic protein progerin will still be there, but the cell learns to cope. It's like giving someone tools to live with a problem rather than removing the problem itself.
That sounds like it could work for other aging diseases too.
That's the real hope. If a longevity gene protects young hearts in progeria, what might it do for an 80-year-old's aging heart? The researchers are already asking that question.
How close are we to actually treating children with this?
Still in the early stages. They've shown it works in mice and human cells in a lab. Gene therapy delivery is the next hurdle—figuring out how to safely get the gene into a child's body. That's years away, probably.
Why does it matter that Sammy Basso lived to 28?
Because it shows progeria isn't absolutely uniform. Some people's bodies resist it longer. Understanding why—and whether this gene played a role—might tell us something about individual variation in the disease.