Researchers have identified a promising new approach to treating a rare and devastating genetic condition that causes children to age at an unusually rapid rate, drawing on the biology of people who live exceptionally long lives. The study shows that “longevity genes, commonly found in centenarians and supercentenarians, may help protect the heart and blood vessels from the severe damage caused by this life-limiting disease. By harnessing mechanisms linked to healthy ageing, the findings offer a fresh and hopeful direction for future therapies.
The research is the first to demonstrate that a gene associated with extreme longevity can slow heart ageing in a model of Hutchinson–Gilford Progeria Syndrome (HGPS). Progeria is a rare and fatal condition in which children develop symptoms of old age within the first years of life, despite appearing healthy at birth. The disease is driven by a mutation in the LMNA gene, which results in the production of a toxic protein called progerin. Over time, progerin accumulates in cells and causes widespread damage, particularly to the cardiovascular system. As a result, most children with progeria die in their teens from heart attacks or strokes, although a small number, such as Sammy Basso, have lived into early adulthood.
Progerin disrupts the structure of the cell nucleus, often described as the cell’s control centre, leading to premature cellular ageing. The heart and blood vessels are especially vulnerable, developing stiffness, scarring, and reduced function. Currently, treatment options are minimal. The only drug approved by the United States Food and Drug Administration is lonafarnib, which reduces the build-up of progerin and modestly extends life expectancy, but does not halt disease progression. Newer clinical trials are exploring drug combinations to improve outcomes.
Rather than attempting to eliminate progerin, the research team explored whether the protein’s damaging effects could be mitigated by strengthening the body’s natural defences. They focused on a longevity-associated gene, LAV-BPIFB4, previously shown to support cardiovascular health during normal ageing. Using genetically engineered mouse models of progeria, the researchers observed early heart problems similar to those seen in affected children. A single administration of the longevity gene significantly improved heart function, particularly the heart’s ability to relax and fill with blood. It also reduced fibrosis, lowered the number of senescent cells, and stimulated the growth of new small blood vessels.
The team then tested the gene in human cells taken from progeria patients and found comparable benefits. Markers of cellular ageing and tissue damage were reduced, even though progerin levels remained unchanged. This suggests the gene helps cells tolerate the toxic effects of progerin rather than removing it directly. The researchers believe this strategy, based on the biology of healthy ageing, could lead to a new class of therapies for progeria and potentially for more common age-related heart diseases. In the longer term, the findings point to the possibility of gene-, protein-, or RNA-based treatments that could improve both survival and quality of life for patients, while also offering insights into how we all age more healthily.
More information: Yan Qiu et al, A longevity-associated variant of the human BPIFB4 gene prevents diastolic dysfunction in progeria mice, Signal Transduction and Targeted Therapy. DOI: 10.1038/s41392-025-02416-3
Journal information: Signal Transduction and Targeted Therapy Provided by University of Bristol
