A gene linked to exceptional longevity has been shown to reverse heart aging in models of Progeria. The finding could inspire new therapies based on the protective genetics of supercentenarians. Credit: Shutterstock
Scientists have uncovered a breakthrough in the fight against a rare genetic condition that causes children to age much faster than normal. The discovery involves "longevity genes" found in people who live exceptionally long lives, often beyond 100 years. Researchers from the University of Bristol and IRCCS MultiMedica found that these genes, which help maintain the health of the heart and blood vessels during aging, could reverse some of the damage caused by this devastating disease.
The study, published in Signal Transduction and Targeted Therapy, is the first to show that a gene from long-lived individuals can slow down heart aging in a model of Progeria. Known scientifically as Hutchinson-Gilford Progeria Syndrome (HGPS), this rare and fatal disorder causes children to exhibit signs of "accelerated aging."
Progeria stems from a mutation in the LMNA gene, which leads to the creation of a harmful protein called progerin. This protein disrupts normal cell function, particularly in the heart and blood vessels. Most affected children die in their teenage years from heart complications, though some, like Sammy Basso -- the oldest known person with Progeria -- live longer. Sammy passed away on October 24, 2024, at the age of 28.
Progerin harms cells by destabilizing their nucleus, the "control center" that manages cell activity. This damage accelerates aging, especially in the cardiovascular system.
At present, the only drug approved by the United States Food and Drug Administration (FDA) is lonafarnib, which reduces the accumulation of progerin. Researchers are now testing a combination of lonafarnib with another experimental drug, Progerinin, to determine whether the two work better together.
Testing Longevity Genes from Supercentenarians
To explore new treatments, Dr. Yan Qiu and Professor Paolo Madeddu of the Bristol Heart Institute collaborated with Professor Annibale Puca's team at IRCCS MultiMedica in Italy. Their goal was to determine if genes from people who live to extreme old age -- supercentenarians -- could protect against the cellular damage caused by Progeria.
The scientists focused on one particular gene, LAV-BPIFB4, which previous research has shown supports healthy heart and blood vessel function during aging.
Using genetically engineered mice that develop Progeria, the researchers observed early heart problems similar to those found in children with the disease. After a single injection of the LAV-BPIFB4 longevity gene, the mice showed improved heart function, particularly in the way the heart relaxes and fills with blood (a process known as diastolic function).
The gene treatment also reduced heart tissue damage, known as fibrosis, and lowered the number of "aged" cells in the heart. In addition, it promoted the growth of new small blood vessels, potentially improving heart health and resilience.
The team then tested the gene on human cells derived from Progeria patients. These experiments revealed that introducing the longevity gene reduced cellular aging and fibrosis without altering progerin levels directly. This suggests that the gene helps cells withstand the toxic effects of progerin rather than eliminating it. The approach strengthens the body's natural defenses instead of attacking the defective protein itself.
A New Approach to Treating Progeria and Heart 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 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. This approach, in time, could also help fight normal 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 aging, which might help us all live longer, healthier lives."
Looking Ahead: Toward New Anti-Aging 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."
