Fight Aging!

A fair number of researchers are investigating the molecular biology of species capable of proficient regeneration without scarring, such as salamanders and zebrafish. It is suspected that mammals retain much of the necessary biology to accomplish feats of regeneration such as regrowing limbs, mechanisms that are in some way blocked in adults, because this sort of regeneration can occur during embryonic development. Researchers here discuss a novel line of research based on the forces exerted on cells due to animal size, and how cells react to those forces. Proficient regeneration occurs in small species, and perhaps that is an important detail.

So what is the difference between animals that can regenerate tissue without scarring, and those that scar? The answer, it turned out, stemmed from something few if any scientists had previously focused on: animal size and the physical forces on their cells. In some small animals - think zebrafish and salamanders - you don't need strong bonds between cells to help them glom onto one another, but when animals grow as large as elephants or dinosaurs, the bonds between cells must be much stronger. Without such strong bonds, even tissues of medium-sized animals, like cats or dogs, would never hold together on the animals' skeleton. It would be like trying to pile pudding on a coat hanger.

"All the animals capable of scarless regeneration have very small bones and their tissues are almost gelatinous. We wondered if these allometric scaling forces might be part of the reason that zebrafish can regenerate tissues, but humans cannot. Allometric scaling forces are known to change bone size and muscle strength, but no one had looked into how they affect tissue regeneration."

To investigate the role of these forces in scarring, the researchers disrupted sensors that all cells have to detect mechanical stresses in their environment. The scientists blocked a molecule called focal adhesion kinase, the most evolutionarily conserved component of this sensing system, and observed how it affected the tissue healing process in pigs, which have the most similar skin to humans, through a very small lesion on anesthetized skin. "To our surprise, simply blocking this one component allowed burn injuries that normally result in scars to heal with completely normal skin architecture and morphology, just like a salamander would."

The researchers are now pursuing clinical trials to reduce scarring in burn patients or also use techniques described in the previously published research to reduce scarring after accidents or surgery. They are also hopeful that looking at these same mechanisms might be useful in helping other organs, such as the lungs, liver and heart, to heal without scarring after injury or disease.

Link https://scopeblog.stanford.edu/2021/10/15/when-it-comes-to-healing-without-scarring-it-pays-to-be-small/