Renewing the Heart - Cardiac Regeneration Through Metabolic Reversal

The human heart is an organ with limited regenerative capacity.
With age, the heart's ability to repair itself after injury decreases, leading to cardiovascular diseases.
New and intriguing research offers a novel approach to treating the aging heart: reducing mitochondrial function in the heart muscle to stimulate regeneration of heart muscle cells (cardiomyocytes).

Metabolic Reversal:

Unlike existing therapeutic approaches, the current study does not focus on enhancing mitochondrial function, but rather on reducing it.
Researchers discovered that reducing the RISP protein, essential for mitochondrial function, causes a metabolic shift in adult cardiomyocytes.
This shift leads to a decrease in oxygen consumption and an increase in glucose consumption, and triggers a process known as "hyperplastic remodeling."
During this process, proliferation of heart muscle cells occurs without an increase in their size.

Therapeutic Effects:

In experiments on mice, reducing RISP not only caused cardiomyocyte regeneration in a healthy heart but also the migration of new heart cells to damaged areas following a heart attack.
These findings indicate enormous potential for treating damaged hearts using this approach.

Molecular Mechanisms:

The study points to several possible molecular mechanisms leading to cardiomyocyte regeneration:

• Epigenetic Changes: A decrease in alpha-ketoglutarate levels (required for TET-mediated demethylation) and an increase in S-adenosylmethionine levels (required for methyltransferase activity) may lead to increased DNA methylation, and consequently to changes in gene expression related to the development and proliferation of heart cells.
• AMPK and mTOR Activity: The absence of AMPK activation (energy supply was maintained) alongside mTOR activation may contribute to the regeneration process.

The current study opens the door to a new and promising therapeutic approach for treating the aging heart.
Reducing mitochondrial function may stimulate 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 efficacy and safety of this approach in humans, but the study findings raise great hope for more effective future treatment of heart diseases.

References: https://www.jci.org/articles/view/165482