The human heart is an organ with a limited ability to regenerate.
With age, the heart's ability to repair itself after injury decreases, leading to cardiovascular disease.
A new and interesting study offers a new approach to treating the elderly heart: reducing mitochondrial function in heart muscle to stimulate regeneration of heart muscle cells (cardiomyocytes).
Reverse metabolism:
In contrast to existing therapeutic approaches, the current research does not focus on strengthening mitochondrial function, but rather on reducing it.
Researchers discovered that the reduction of the RISP protein, essential for mitochondrial function, causes a change in metabolism in mature cardiomyocytes.
This change causes a decrease in oxygen consumption and an increase in glucose consumption, and leads to a process known as "hyperplastic remodeling".
During this process, a proliferation of heart muscle cells occurs without increasing their size.
Therapeutic effects:
In experiments in mice, reducing RISP caused not only the regeneration of cardiomyocytes in a healthy heart, but also the migration of new heart cells to damaged areas following a heart attack.
These findings indicate a huge potential for treating damaged hearts using this approach.
Molecular mechanisms:
The study indicates several possible molecular mechanisms leading to cardiomyocyte regeneration:
- Epigenetic changes: A decrease in alpha-ketoglutarate levels and an increase in S-adenosylmethionine levels may lead to changes in DNA demethylation, and accordingly to changes in gene expression related to the development and proliferation of heart cells.
- AMPK and mTOR activity: Decrease in AMPK activity and increase in mTOR activity may contribute to the regeneration process.
The current study opens the door to a new and promising therapeutic approach to the treatment of an elderly heart.
Decreasing mitochondrial function may stimulate the regeneration of heart muscle cells, both in a healthy heart and in a damaged heart after a heart attack.
Further research is needed to investigate the effectiveness and safety of this approach in humans, but the research findings raise great hope for more effective future treatment of heart disease.
References: https://www.jci.org/articles/view/165482
