It is well known that "lizards can regenerate even if their tails are cut off", but there is another species on Earth with extraordinary abilities that can be called "regeneration champions". It is an amphibian "salamander". Not only can they regenerate their own legs, but they can also regenerate their own eyes, brains, hearts, and other organs, and they can do so repeatedly.
Researchers have long been fascinated by the salamander's fantastic regenerative abilities, but they are also said to be "out of the ordinary creatures", and many of their mechanisms remain a mystery.
Four years ago, however, a major discovery upended common sense in biology. The secret of regeneration is found in red blood cells. In mammals, red blood cells specifically carry oxygen, but in salamanders, it has been found that they may have a "time-reversal" effect on cells near wounds, allowing them to rebuild the body. What exactly is this unique regenerative ability of salamanders?
There are high hopes that if the secrets of salamanders' regenerative abilities can be unlocked, they can be used in regenerative medicine for humans.
Unconventional " forces, regenerated again and again
Salamanders can regenerate a lost leg in about five months and a partially damaged heart in about a month without leaving any scars. There is also evidence that the legs and eyes can even regenerate function. In addition, they can regenerate themselves multiple times in a lifetime, a mechanism that is unimaginable in common sense.
It is well known that lizards can regenerate even after their tails are cut off, but the mechanisms of lizards and salamanders are completely different. The lizard originally had a gap in its tail that would fall out when enemies appeared. This allows them to escape when the enemy is distracted.
New cartilage, shaped like a stick, grows out from the tail of the shedding lizard to balance the body. This is an ability that lizards acquire during their evolution.
On the other hand, the salamander's body does not have pre-designed shedding parts, and new tissue is born from the wound. It is uncertain whether other creatures originally possessed this amazing ability to regenerate, or whether, in the course of evolution, only salamanders suddenly acquired this ability.
Research is currently underway to study the regenerative system of salamanders from all possible methods, and it is hoped that if this "unique regenerative mechanism" can be elucidated, it may be applied to regenerative medicine in humans.
In fact, frogs and salamanders, which belong to the same amphibian family as salamanders, also have a strong regenerative capacity during their growth.
The key to this is the "stem cells" that actively work in the body during growth.
Cells in an organism divide from the so-called "fertilized egg" (a common type of cell) into "stem cells," such as bones and muscles. For example, muscle stem cells are further divided into palm and fingertip muscles. This is called differentiation, and once a cell differentiates and becomes a muscle in a certain part of the body, it does not revert to muscle stem cells.
We humans also say that stem cells are active in the fetus, and they regenerate even if the ventricles of the heart are damaged.
However, in many organisms, the regenerative power of stem cells weakens when they have grown up and their bodies are intact. In the case of salamanders, stem cell activity is also weakening, so why are only salamanders able to regenerate their bodies again and again in their lifetime?
Time Reversible "The Secret of regeneration systems
It is well known that once a stem cell is differentiated, it cannot become like the original stem cell, but this is not the case with salamanders.
For example, when the muscles of a salamander's arm are injured, cells that have differentiated into muscles in a specific area near the wound, the arm, can revert to "stem cell-like" cells of muscle. It's like the cells taking a step backwards, like going back in time.
From this state, they can be transformed into various muscles, such as the muscles of the fingertips. The resulting stem cell-like cells create a miniature prototype in the area near the wound, place the necessary muscle cells, and then grow to an honorable size. This remarkable phenomenon is called "de-differentiation.".
Studies to date have confirmed that dedivisibility occurs in the muscles of the legs and the nerves of the eyes. However, it is thought that it can occur throughout the body, including in the bones and skin.
The combination of "stem cells" and "dedifferentiation" is currently being studied to elucidate the detailed mechanism by which the combination of "stem cells" and "dedifferentiation" produces the amazing regenerative abilities unique to salamanders.
A great discovery in biology! It was the "red blood cells" that gave the order to dedivision!
Professor Chikafumi Chiba (University of Tsukuba) is trying to unravel the mystery of how salamander cells "de-differentiation". Qianye believes that the secret lies in genes, and spent six years studying all the genes in the salamander's body. He found that there was only one gene specific to salamanders, Newtic1, which no other animals had.
We named this gene "Newtic1", combined with "newt", which means salamander in English because it was the first gene we discovered. We hope that Newtic1 can play a key role in regeneration."
When Chiba photographed the regeneration of salamander wounds with a laser microscope, he found that a month later, the protein produced by Newtic1 (Newtic1 protein) had gathered in the area of active regeneration.
In addition, when the cells were viewed in three dimensions with a high-power microscope, it was found that the Newtic1 protein surrounded the nucleus like a rubber band.
What exactly are these cells?
In mammals, including us humans, red blood cells are supposed to be specialized in transporting oxygen and have nothing to do with body regeneration, but a closer look reveals that the red blood cells of salamanders have a "nucleus," which is not found in human red blood cells, and they produce all sorts of things. This is a discovery that subverts common sense in biology.
It's so out of the ordinary that the red blood cells are actively secreting something, a factor related to regeneration. I don't think it was unexpected, but a story that no one had imagined before."
A closer examination of salamander red blood cells revealed the presence of at least 10 important proteins involved in regeneration. In addition, a closer examination of the Newtic1 protein revealed that it looked like a rubber band surrounding red blood cells and was small and granular. From this, Chiba drew up a plan.
When red blood cells reach the wound, the proteins involved in regeneration enter the particles produced by Newtic1. These particles act as "carriers", so to speak, releasing proteins involved in extra-erythrocyte regeneration to where they are needed. This opens up de-differentiation and supports unparalleled regenerative capacity. While still in the hypothetical phase, we are starting to see some of the amazing regenerative abilities that researchers have been chasing.
Chiba also found that humans also have substances involved in regeneration, and Newtic1 is selectively transported from red blood cells. If this is the case, the miraculous mechanism of the salamander should be harnessed to provide regenerative medicine for us humans. Chiba is working to reveal more detailed mechanisms for application in regenerative medicine.
We researchers hope to prove the hypothesis of a salamander regeneration system and in the future find out the detailed formulation of the substances made by Newtic1 and the time they are delivered to the regeneration site to find out why humans have the same substance but can't regenerate like salamanders, and how we can do that." We also want to establish a medical technology that delivers the substances needed for regeneration to the wound by means of ointments, injections or intravenous drips" (Chiba).
On the other hand, he said, it is also questionable whether this amazing regenerative ability is beneficial to salamanders.
As mentioned above, a missing leg takes more than five months to retrow before being eaten by an enemy, which makes it have little to escape. In other words, they believe that their ability to regenerate is not very useful in nature.
Even humans, who have a strong regenerative capacity during the fetal period, lose this ability when they grow out of their mother's belly. It is thought that the evolutionary process made it more advantageous for humans to leave scars and close wounds on land. So, how do salamanders gain this regenerative ability? It's hard to imagine" (Chiba).
Genome-wide analysis reveals the secrets of regenerative power
The secret of the salamander's regenerative ability has been uncovered, and the latest research is now underway to find out its secrets through "whole genome analysis".
The Amphibian Research Center at Hiroshima University is conducting research on whole-genome analysis of salamanders, which has a unique facility called "Salamander Farms" with more than 1,000 salamanders at any one time.
The genome is all the genetic information, where genes are the blueprints of proteins, and by studying the function of parts other than genes, the aim is to find the key to the regenerative ability of salamanders.
Salamander farms raise salamanders are the Iberianto kai salamander, one of the largest salamanders in the world, living in Spain and other countries. They can produce up to 600 eggs at a time, grow rapidly, and can multiply in a short period of time, producing a large number of uniform eggs from the same parents, making it possible to effectively conduct genetic and other studies.
The decoding of the entire genome, which requires a lot of work, has been achieved overnight, and all the nucleotide sequences have been revealed.
Then, thanks to the detailed study of the sequence, what emerges is the phenomenon of "reverse transcription genes", in which parts of the genome are copied and pasted elsewhere. This happens so often that the salamander's genome has grown to more than seven times that of the human genome. The repetitive part of the genome produced by the reverse transcriptase son was previously considered a useless part that had no function.
However, it has now been found that the most regenerative salamander, like salamanders, has a very large number of genome repeats produced by reverse transcription genes, and it can now be considered that they have a very important role. Toshinori Hayashi (Professor at the Center for Amphibian Research at Hiroshima University), a researcher in regenerative biology, said
Some people say that the size of the genome of salamanders is due to the large amount of repetitive sequence junk, and the size of the genome is meaningless. By analyzing the entire genome in detail, Hayashi and his team are trying to uncover the secrets behind the extraordinary regenerative abilities of these creatures, for example, looking for common ground between them.
We don't know why salamanders have extraordinary regenerative abilities or whether other creatures have ever had them, but we are captivated by the salamander's mysterious mechanism. Thanks to years of hard work by researchers, part of the mechanism behind regenerative capacity has been revealed, and it may not be long before a new regenerative medicine that has never been seen before is born.
Follow us in our private message for more information on regeneration