By Morgan Nwanguma
Scientists have uncovered a major breakthrough in understanding — and potentially treating — Hutchinson-Gilford Progeria Syndrome (HGPS), a rare disorder that causes children to age at an astonishing pace. The discovery centers on a “longevity gene” found in people who routinely live past 100, and in some cases beyond 110, known as supercentenarians.
In a new study published in Signal Transduction and Targeted Therapy, researchers from the University of Bristol and IRCCS MultiMedica report that this gene can reverse key aspects of heart ageing in models of Progeria. When introduced into Progeria-affected cells and into mice engineered to develop the disease, the gene restored heart function, reduced tissue damage, and slowed the progression of aging symptoms.
Progeria is caused by a mutation in the LMNA gene, which produces a toxic protein called progerin. Progerin destabilizes the cell nucleus — the command centre of the cell — leading to widespread cellular damage, especially in the heart and blood vessels. Most children with Progeria die from cardiovascular complications in their early teens. A few live longer, including Sammy Basso, the oldest known person with the disease, who passed away on October 24, 2024, at age 28.
While the only FDA-approved treatment, lonafarnib, slows progerin accumulation, it does not fully stop disease progression. Researchers are now evaluating a combination therapy that pairs lonafarnib with an experimental drug called Progerinin.
Seeking a new approach altogether, Dr. Yan Qiu and Professor Paolo Madeddu of the Bristol Heart Institute partnered with Professor Annibale Puca’s team in Italy to test whether genetic variants carried by exceptionally long-lived individuals could counteract Progeria’s cellular damage. They focused on a gene called LAV-BPIFB4, already known to support heart and blood vessel health during aging.
In Progeria-model mice, a single injection of LAV-BPIFB4 significantly improved diastolic heart function — the heart’s ability to relax and fill with blood. It also reduced fibrosis (scarring), lowered the number of prematurely aged cells, and stimulated the formation of new microvessels. When applied to human cells derived from Progeria patients, the gene decreased cellular ageing and fibrosis without reducing progerin itself, suggesting it strengthens cells’ natural defenses against the toxic protein rather than trying to eliminate it.
This longevity-gene strategy represents an entirely new way to treat both Progeria and age-related heart decline. By harnessing biological traits that naturally protect long-lived humans, scientists hope to pave the way for safer, more effective therapies — and possibly reshape how we think about treating not only rare genetic diseases but also normal aging.
Dr. Yan Qiu, Honorary Research Fellow in the Bristol Heart Institute at the University of Bristol, said: “Our research has identified a protective effect of a “supercentenarian longevity gene” against Progeria-related heart dysfunction in both animal and cell models.
“These findings point to a new kind of therapy for Progeria — one that taps into the natural biology of healthy aging rather than simply targeting the faulty protein. In the long run, this strategy may also offer benefits for treating age-related heart disease.”
“Our research brings new hope in the fight against Progeria and suggests the genetics of supercentenarians could lead to new treatments for premature or accelerated cardiac ageing, which might help us all live longer, healthier lives.”
Looking Ahead: Toward New Anti-Ageing Therapies
Professor Annibale Puca, Research Group Leader at IRCCS MultiMedica and Dean of the Faculty of Medicine at the University of Salerno, added: “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. Looking ahead, the administration of the LAV-BPIFB4 gene through gene therapy could be replaced and/or complemented by new protein- or RNA-based delivery methods.
“We are currently conducting numerous studies to investigate the potential of LAV-BPIFB4 in counteracting the deterioration of the cardiovascular and immune systems in various pathological conditions, with the goal of translating these experimental findings into a new biologic drug.”
English