Younger heart with longevity protein

Article by SoLongevity Research
A genetic variant very common in centenarians appears to have the ability to restore the function of certain heart cells, improving overall organ function and turning back the hands of the biological clock

What this article is about

  • LAV-BPIFB4 gene variant is frequent in people over 100 years old
  • By administering the protein encoded by this gene on cardiac cells, there is an improvement in their function
  • A similar effect occurs on old and middle-aged mice, whose hearts appear to be rejuvenated by ten years

What do studies on centenarians show?

Rejuvenation is a complex concept. And at the moment it is also an unachievable goal. Yet there are many research groups around the world working on individual organs and systems to understand what accounts for the longevity of some individuals, those ultracentenarians who, thanks to the characteristics of their DNA, live healthier than average. Thus, just by analyzing the genetic makeup of “super seniors,” a research team has discovered how to counteract theaging of the heart. Going so far as to “rejuvenate” it by almost ten years. The finding comes from a study published in Cardiovascular Research, coordinated by Hannibal Puca of the MultiMedica Group in Milan and Paolo Madeddu of the University of Bristol.

What is LAV-BPIFB4 protein and its long-lived variant?

The subject of the study, conducted both in an animal model (i.e., in mice) and in vitro, i.e., in cultured cells, is one of the so-called “longevity proteins“. It is called LAV-BPIFB4, and alongwith sirtuins, it appears to underlie long life. The gene encoding the BPIFB4 protein, in its LAV (Longevity Associated Variant) variant, is indeed common in people over 100 years old. This variant was identified by Hannibal Puca, laboratory head at IRCCS MultiMedica, who also discovered its potential in preventingatherosclerosis and rejuvenating the immune system.

The gene encoding the BPIFB4 protein, in its LAV – Longevity Associated Variant, is common in people over 100 years old

Is it possible to rejuvenate heart cells?

The in vitro analysis conducted by the Italian group compared heart cells from elderly patients with heart problems to those from healthy individuals. In the first group, pericytes, i.e., the cells that support the construction of new blood vessels, were found to perform less well and age more, the researchers explained. By adding LAV-BPIFB4 protein to these cells,” they add, “there was a rejuvenation process. The pericytes of elderly and sick patients resumed proper function, proving more efficient in inducing new blood vessels.

What does the mouse study add?

In parallel with this analysis, the Bristol group carried out the in vivo study in the animal model. The researchers administered the LAV-BPIFB4 protein to older mice to induce rejuvenation, and to middle-aged mice to prevent aging. And they noted improved vascularization, more efficient blood flow and decreased fibrosis. A phenomenon that, on humans, would be equivalent to having a younger heart by about 10 years. If this action were also confirmed by other studies, the authors conclude, therapy with LAV-BPIFB4 protein could be considered for rejuvenation not only of the vascular and immune systems but also of the heart pump.


Monica Cattaneo, PhD, Antonio P Beltrami, PhD, MD, Anita C Thomas, PhD, Gaia Spinetti, PhD, Valeria Alvino, PhD, Elisa Avolio, PhD, Claudia Veneziano, PhD, Irene Giulia Rolle, PhD, Sandro Sponga, MD, Elena Sangalli, PhD, Anna Maciag, PhD, Fabrizio Dal Piaz, PhD, Carmine Vecchione, MD, Aishah Alenezi, PhD, Stephen Paisey, PhD, Annibale A Puca, MD, Paolo Madeddu, MD, “The longevity-associated BPIFB4 gene supports cardiac function and vascularization in aging cardiomyopathy”, Cardiovascular Research, 2023, cvad008, https://doi.org/10.1093/cvr/cvad008.

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