Supercentenarian Gene Offers Hope for Children With Progeria

Hutchinson-Gilford Progeria Syndrome (HGPS) is one of the rarest and most tragic genetic disorders, caused by a mutation in the LMNA gene. This mutation leads to the build-up of a toxic protein called progerin, which weakens the cell’s nucleus and accelerates ageing. Children with HGPS develop signs of old age, such as wrinkled skin, hair loss, and heart disease, within just a few years of life, and most die in their early teens due to cardiovascular complications. The case of Sammy Basso, who lived until 28, stands as a remarkable exception.

Currently, Lonafarnib, an FDA-approved drug that slows progerin buildup, offers limited relief but not a cure. Currently, the research is focused on reversing the effects of ageing and going beyond simply controlling symptoms (1^✔ ✔Trusted Source
A longevity-associated variant of the human BPIFB4 gene prevents diastolic dysfunction in progeria mice

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The “Longevity Gene” from Supercentenarians

The genes of supercentenarians (individuals who survive past 110 in fine health) were the main driving force behind this research. Their exclusive type of gene, LAV-BPIFB4, has been demonstrated to extend the lifespan and enhance cardiovascular well-being in experimental animals.

Interestingly, HGPS cells contain low amounts of BPIFB4, which is probably inhibited by progerin. The hypothesis made by researchers was that replacing BPIFB4 could overcome the toxicity of progerin and enhance heart performance.

Gene Therapy Restores Heart Health in Progeria Mice

Using a gene therapy vector (AAV9-LAV-BPIFB4), scientists treated mice carrying the human LMNA mutation. The results were striking:

• Better heart function: The treated mice exhibited improved diastolic function.
• Less fibrosis: The hearts had fewer scar-like fibrotic tissues and healthier blood vessels.
• Reduced cell ageing: Markers of cell senescence (p16, p21) dropped significantly after treatment.

In lab-grown fibroblast cells from HGPS patients, the LAV-BPIFB4 gene reduced ageing-related damage and improved cell survival without changing progerin levels. It worked mainly by dampening harmful signalling pathways linked to fibrosis and inflammation.

How Does This Work?

The mechanism by which LAV-BPIFB4 restores some regularity to the nuclear and nucleolar processes—a domain implicated with progerin—seems to occur internally within cells. Additionally, it can send protective signals to the surrounding tissues and helps shield the heart muscle cells.

This is essentially a supercentenarian gene that keeps the cells resilient and youthful even in a situation mimicking progeria, or old age.

A Step Toward Reversing Premature Aging

This is the first study to show that a naturally existing longevity gene can protect the heart from progeria-related damage. Despite being in its early stages, the results are promising for the potential application of LAV-BPIFB4 gene therapy to enhance or augment existing therapeutic approaches, such as Lonafarnib, in the future.

As researchers continue to study gene therapy and DNA-base editing, it may be possible to slow down—or perhaps reverse—premature ageing by fusing precision medicine with even these supercentenarian-inspired genes.

The world's oldest and fittest individuals' biology led researchers to a discovery that might shield progeria sufferers' youthful hearts from the disease's assault and, eventually, the passage of time.

Reference:

1. A longevity-associated variant of the human BPIFB4 gene prevents diastolic dysfunction in progeria mice - (https://pmc.ncbi.nlm.nih.gov/articles/PMC12480688/)

Source-University of Bristol