Researchers report that a variant of the BPIFB4 gene enriched in long‑lived people improved markers of heart health in mouse and cell models of Hutchinson–Gilford progeria syndrome, suggesting a potential new path for therapy.
Progeria, or Hutchinson–Gilford Progeria Syndrome (HGPS), is a fatal disorder caused by mutations in the LMNA gene that produce an abnormal protein called progerin. Progerin destabilizes the cell nucleus and drives premature aging, with most deaths due to cardiovascular disease in the second decade of life. (medlineplus.gov)
The only U.S. Food and Drug Administration–approved medicine is lonafarnib (Zokinvy), a farnesyltransferase inhibitor used as standard care. A Phase 2a trial now enrolling at Boston Children’s Hospital is evaluating progerinin alongside lonafarnib versus lonafarnib alone. (progeriaresearch.org)
In a peer‑reviewed letter published September 29, 2025, in Signal Transduction and Targeted Therapy, scientists from the University of Bristol and IRCCS MultiMedica tested a longevity‑associated variant of BPIFB4 (LAV‑BPIFB4) in progeria mouse models and patient‑derived cells. After a single AAV9‑mediated injection of LAV‑BPIFB4, mice showed improved diastolic function, reduced perivascular fibrosis, fewer p16/p21‑positive senescent cells, and increased small‑vessel density; systolic function was unchanged. In patient fibroblasts, LAV‑BPIFB4 reduced senescence and fibrotic signaling without lowering progerin itself, indicating protection from progerin toxicity rather than its removal. (dx.doi.org)
The study builds on prior work linking LAV‑BPIFB4 to healthier cardiovascular aging and vascular support in preclinical settings. (heart-institute.bristol.ac.uk)
“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 ageing rather than blocking the faulty protein,” said Dr. Yan Qiu of the Bristol Heart Institute, according to the University of Bristol. (bristol.ac.uk)
Professor Annibale Puca of IRCCS MultiMedica added that the findings point to “new treatment strategies for this rare disease,” noting that gene therapy delivery could be complemented by protein‑ or RNA‑based methods in the future. (eurekalert.org)
The research also references the late Italian biologist and advocate Sammy Basso, who lived with classic progeria to age 28 and died on October 5, 2024. His life underscored both the disease’s burden and the gains from modern care. (progeriaresearch.org)
While these results are preclinical, they suggest a complementary approach to existing therapies—enhancing cellular resilience to progerin’s damage rather than directly suppressing the protein. Clinical translation will require safety and efficacy studies of gene‑, protein‑, or RNA‑based delivery of LAV‑BPIFB4.