A gene from 100-year-olds could help kids who age too fast
Researchers have made a significant discovery regarding a gene associated with exceptional longevity that demonstrates the ability to reverse cardiac aging in models of Progeria, a severe condition leading to rapid aging in children. By incorporating this gene from supercentenarians into cells and mice affected by Progeria, scientists successfully restored cardiac performance, minimized tissue injury, and mitigated symptoms of accelerated aging. This breakthrough paves the way for innovative treatments drawn from the inherent biological mechanisms of individuals who enjoy prolonged lifespans, potentially transforming approaches to managing rare disorders as well as typical age-related decline.
A gene connected to remarkable long life has proven effective in counteracting heart aging in experimental models of Progeria. This advancement may lead to novel therapeutic interventions leveraging the safeguarding genetic traits of those who reach supercentenarian status.
Experts have identified a major step forward in combating a uncommon genetic disorder that accelerates aging in young children far beyond normal rates. This involves genes dubbed ‘longevity genes’ present in individuals who achieve extraordinary ages, surpassing 100 years. Teams from the University of Bristol and IRCCS MultiMedica revealed that such genes, which sustain cardiovascular and vascular health through the aging process, possess the capacity to undo certain harms inflicted by this tragic illness.
The research, featured in Signal Transduction and Targeted Therapy, marks the initial demonstration that a gene derived from long-lived people can decelerate cardiac aging within a Progeria model. Clinically termed Hutchinson-Gilford Progeria Syndrome (HGPS), this infrequent and lethal ailment induces manifestations of swift aging in affected children.
HGPS arises from a mutation in the LMNA gene, resulting in the production of a detrimental protein known as progerin. This aberrant protein impairs standard cellular operations, with pronounced effects on the heart and vascular system. The majority of children with this condition succumb in adolescence due to cardiovascular failures, although exceptional cases like Sammy Basso, recognized as the longest-surviving Progeria patient, endured longer. Sammy Basso died on October 24, 2024, aged 28.
Progerin inflicts cellular harm by compromising the stability of the nucleus, the cellular command hub that oversees vital functions. Such disruption hastens aging processes, particularly within the cardiovascular framework.
Currently, lonafarnib stands as the sole FDA-approved medication, which works by diminishing progerin buildup. Ongoing trials are evaluating lonafarnib paired with an investigational agent, Progerinin, to assess enhanced efficacy in combination.
Testing Longevity Genes from Supercentenarians
In pursuit of novel remedies, Dr. Yan Qiu and Professor Paolo Madeddu from the Bristol Heart Institute partnered with Professor Annibale Puca’s group at IRCCS MultiMedica in Italy. Their objective centered on evaluating whether genes from supercentenarians could shield against Progeria-induced cellular deterioration.
The investigation targeted the LAV-BPIFB4 gene, prior studies of which have established its role in preserving optimal heart and vessel functionality amid aging.
Employing mice genetically modified to manifest Progeria, the researchers noted incipient cardiac issues mirroring those in pediatric patients. Following administration of a single dose of the LAV-BPIFB4 longevity gene, the animals exhibited enhanced cardiac performance, especially in diastolic function—the critical phase where the heart relaxes and replenishes with blood.
This genetic intervention further diminished myocardial fibrosis, decreased senescent cell populations in cardiac tissue, and stimulated angiogenesis, fostering new microvasculature that bolsters overall cardiac vitality and durability.
Subsequently, the researchers applied the gene to human Progeria patient-derived cells. These tests indicated that the longevity gene mitigated cellular senescence and fibrosis without directly impacting progerin concentrations. This implies the gene fortifies cellular resilience against progerin’s toxicity, bypassing the need to eradicate the faulty protein and instead augmenting innate protective mechanisms.
A New Approach to Treating Progeria and Heart Aging
Dr. Yan Qiu, Honorary Research Fellow at the University of Bristol’s Bristol Heart Institute, commented: “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, stated: “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.”
