Winding back the clock on your old ticker
Researchers at the University of Bristol (Bristol, UK) and the MultiMedica Group (Milan, Italy) have found genetic mutations in centenarians can be utilized in gene therapy to rejuvenate damaged cardiac tissues. This has the potential for the future treatment of heart disease.
From the age of 20, your heart muscle starts to decline in function due to the aging process. This leads to the decline of athletic ability and ultimately can lead to cardiac issues such as heart failure. There are patterns across the world of areas referred to as ‘blue zones’ where people often live past the age of 100 and these groups of individuals are also less prone to cardiac issues. Previous research has shown that centenarians from these ‘blue zones’ carry genetic mutations, which scientists believe protect the heart muscle from age-related diseases.
Researchers from Bristol University, in association with the British Heart Foundation, recently published a paper in Cardiovascular research showing a gene therapy using one of these advantageous genetic mutations was able to improve the cardiac functionality of aged mice. The researchers administered an adeno-associated virus carrying a longevity-associated variant (LAV) of the bactericidal/permeability-increasing fold-containing-family-B-member-4 gene (BPIFB4) to both middle-aged and elderly mice.
The results of the study showed that the middle-aged mice experienced stagnation of the aging process after a single administration. Further to this, when the gene therapy was applied to elderly mice with similar loss of function seen in elderly patients’ hearts, the level of invigoration to the mouse hearts observed was estimated to be equivalent to a reduction of ten years of age in the human heart.
Furthermore, the MedMedica research group carried out a three-year in vitro study showing equally promising results. Recombinant LAV-BPIFB4 protein was administered to heart cells taken from elderly patients with various cardiac issues and the functionality of these cells was then compared with those of healthy individuals. It was observed that the pericytes, which are cells involved in the production of new blood vessels, had increased function leading to the rejuvenation of the cardiac cells.
Paolo Madeddu, head of the Bristol team, had this to say about the results of the research: “Our findings confirm the healthy mutant gene can reverse the decline of heart performance in older people”.
The researchers have high hopes for the future; they believe that other gene mutations could also be found in centenarian populations, which may have a similar or superior ability to reverse the functional decline of the heart muscle in patients.
Annibale Puca, Head of the laboratory at the Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) MultiMedica and Professor at the University of Salerno (Baronissi, Italy), commented: “We have a new confirmation and enlargement of the therapeutic potential of the gene/protein. We hope to test its effectiveness soon in clinical trials on patients with heart failure.”
The teams have also recently received funding from the Medical Research Council (UK), as well as the British Heart Foundation and Diabetes UK, for further treatments of genetic diseases such as Hutchinson-Gilford syndrome, a disease that causes premature aging of the heart and blood vessels in children, as well as diabetes.
The team also wants to transition into protein therapies. Madeddu added: “We are now interested in determining if giving the protein instead of the gene can also work. Gene therapy is widely used to treat diseases caused by bad genes. However, a treatment based on a protein is safer and more viable than gene therapy”.