Weizmann Institute of Science scientists discovered that the temporary aging of certain cells in the heart is essential for the regeneration of the body's blood pump
When it comes to blood circulation in the body, the heart muscle cells are the main players. Therefore, it is no wonder that the efforts in the field of heart rehabilitation are focused on trying to make damaged heart muscle cells regenerate. A study by Weizmann Institute of Science scientists, recently published in the scientific journal Circulation, draws attention to a group of cells that is less in the spotlight - the fibroblasts, cells known mainly for the structural support they provide to the heart muscle, and make up about half of the cells in this organ. It is now becoming clear that these cells may play a key role in heart rehabilitation.
Mammals, including humans, do not have the ability to regenerate their heart tissue. Therefore, as soon as the heart muscle cells are damaged, for example in the case of myocardial infarction ("heart attack"), they die and are replaced by scar tissue, which is unable to contract, and therefore cannot participate in the vital pumping action of the heart. The staff scientist, Dr. Rachel Serig, from Prof. Eldad Tzhor's laboratory in the Department of Molecular Biology of the Cell, studied unique situations in which the heart muscle can actually regenerate - for example, in the first week of a mouse's life or in the heart of adult zebrafish. Dr. Serig discovered Because under these conditions, some fibroblasts temporarily go into a state of a kind of aging (in English: senescence) in which they no longer divide, but also do not dead
Cellular aging is associated with the aging of the body and with various disease states. However, it is now known that in its temporary form it is essential for many processes related to fetal development. With the help of research student Racheli Rimer and other group members, Dr. Sarig found evidence that this transitory state of "temporary aging" may also be beneficial for heart rehabilitation.
The scientists identified "aging" cells in adult zebrafish and newborn mice, as well as in adult mice injected into their damaged heart muscle with agrin - a protein that was previously discovered in Prof. Zachor's laboratory as a cause of heart muscle regeneration. In the three cases examined, the signs of aging disappeared or decreased significantly after about three weeks.
"The aging fibroblasts can promote healing by secreting growth factors and other molecules that help healing, or by recruiting immune system cells that also contribute to healing," says Dr. Serig. "However, a state of cellular aging that lasts too long may also lead to inflammation chronic and other unwanted effects, therefore he must be under close control."
The timing of cellular senescence, which in each case coincided with the timing of heart regeneration, indicates that this transient state is essential for heart regeneration - just as it is essential for tissue regeneration in salamanders as well. The fact that temporal aging has been conserved throughout evolution, from zebrafish to mammals, also highlights the importance of this process.
The scientists found that the control of temporary aging in the heart muscle is done by the p53 gene, the tumor suppressor which is known as the "guardian of the genome", but also performs other functions in the cell. The activity of a particular version of p53 increased in cells that had undergone temporal senescence.
"Our findings indicate that p53 activity may serve as a marker for temporary cellular aging in the heart muscle," says Prof. Tzhor. "When we learn more about the mechanisms of this aging, it may be possible to control the process to promote heart muscle recovery."
The research group of Prof. Karina Yaniv from the Department of Biological Control was a partner in this project.
