Turning back the clock on heart cells

Feeling pumped – enabling the heart to gain regenerative capabilities could offer hope for heart attack victims and those suffering from cardiovascular disease.

It’s World Heart Day and what better way to mark the day than to report on the latest longevity heart research? Researchers from the Max Planck Institute for Heart and Lung Research have demonstrated they can return adult cardiomyocytes to a foetal-like state in mouse models. Cardiomyocytes are the cells responsible for generating contractile force in the heart.

Longevity.Technology: This research could have wide-reaching consequences It raises the hope that it will eventually be possible to repair or regrow muscle lost in heart attacks or heart disease. Given that every year an estimated 17.9 million people die globally as a result of cardiovascular diseases (CVDs) [1], being able to repair heart damage should make a dent in this total. Beyond the heart, these rejuvenation techniques may also be applicable to other organs or tissues.

Heart cells are some of the most inflexible cells in the body and unlike liver or muscle cells, they do not regenerate when they are injured. Add into the mix the fact that cardiomyocyte replacement can be extremely slow in adult hearts – almost as if they actively resist cell division – and any sort of healing of damaged myocardium post-injury, becomes difficult.

However, foetal hearts are able to regenerate because their cardiomyocytes are less mature and can still proliferate.

Lead researcher Thomas Braun and his team bio-engineered mice so that they can express Yamanaka factors, but only as a result of being fed a particular antibiotic. The four genes selectively expressed – Oct4, Sox2, Klf4 and c-Myc (OSKM) – lead to cell renewal, but it’s a tricky process, as too much expression can lead to dangerous tumours.

The research meant that the team where able to induce a gene expression programme in the hearts of adult mice to have the capability for cardiomyocyte regeneration.

When the mice suffered induced heart attacks, the heart-specific expression of OSKM for a short period of time either before or immediately after aided the regeneration of cardiomyocytes. The researchers also noted a significant reduction in scar sizes and improved cardiac function.

However, only mice that had been pre-treated, or those receiving the antibiotic straight after an attack showed improved levels of cardiac function. Mice that received the antibiotic trigger six days after the heart attack did not show any significant improvement.

“Short-term OSKM expression before and during myocardial infarction ameliorates myocardial damage and improves cardiac function, demonstrating that temporally controlled dedifferentiation and reprogramming enable cell cycle re-entry of mammalian cardiomyocytes and facilitate heart regeneration,” explained the research team [2].

This research is in its infancy, but is further evidence that Yamanaka factors and rejuvenation at a cellular level hold great promise for longevity.
[1] https://www.who.int/health-topics/cardiovascular-diseases/#tab=tab_1
[2] https://www.science.org/doi/10.1126/science.abg5159

Image by S. Hermann & F. Richter from Pixabay