Throughout history, humankind has been concerned with ensuring longevity and perpetual youth. In Norse mythology, Idun is the keeper of apples and the giver of eternal youth. In Japan, there is the legend of Habyako Bikuni, the 800-year-old nun who remained young. All her life after eating mermaid meat by mistake.
We also find that the same idea was an obsession with the greatest thinkers, philosophers, and novelists throughout our history, and of course since the advent of contemporary medicine, the same concerns were strongly present, except that a study published a few days ago in the prestigious "Cell" journal takes this idea to a truly unique new area. In this study, old mice that were blind regained their sight, their brains became smarter and younger, and their bodies built muscle tissue and healthier kidneys!
There is even stranger things, as David Sinclair, professor of genetics at the Blavatnik Institute at Harvard Medical School, and his colleagues in their experiments were able to accelerate aging rates in mice so that they reach old age a few weeks after their birth!
But most important of all is the hypothesis Sinclair pioneered more than a decade ago, which, if confirmed, would be seen as a revolution in gerontology.
Picture of Sinclair's twin mice, the mouse below has been treated to age faster compared to its sibling.
(communication Web-sites)
What really is aging?
Traditionally, theories explaining aging have been based on one basic idea: we age simply because our DNA wears down with time.
DNA is simply the code of life that you inherit from your parents.
Imagine your body as a movie shown on the screen. This film originally consists of a long tape, on which the scenes are encoded. Here the hero meets his beloved for the first time, and here he confesses his love to her, and in a third place on the tape she leaves him to his sorrows alone.
Our human cells also contain a two-meter long strip of chemical units that represent DNA. Each group of these units represents a gene. Here is a gene that expresses the color of your hair, here another gene that expresses the color of your eyes, and there is a gene that expresses the length of your bones...etc, down to the smallest detail. Molecular morphologies and chemical reactions in our bodies.
Over time, this long tape of information experiences a set of mutations. Usually these mutations are not useful and allow gradual damage to the DNA. If one of the films you love was loaded on a compact disc, the frequent use, exposure to weather conditions, and the nature of the material of the disc itself pushes it with time. To become less good, it will work slowly, its reaction will be delayed, and from time to time some scenes may stop or break, and at some point it will stop working completely.
Likewise, our DNA is damaged with time, and accordingly, the functions of the cells are damaged, and at some point everything stops, and we die.
However, Sinclair believes that this hypothesis is completely wrong. It is not the information loaded on our DNA that is damaged (and by extension, this is an almost impossible error to fix), but something else.
This brings us back to DNA again. As we mentioned, it is very long compared to the very small size of the cell. It is enough for you to know that every square centimeter of your skin contains 100,000 cells. How can all this tape be placed within this very narrow space?
road signs
Because our DNA is so long, it gets wrapped around proteins called histones. In the same way that you wind a string on a pulley, those histones are grouped into larger clumps called chromosomes.
green for histones, blue for DNA (communicating sites)
The problem of scientists has always been to ask why the body's cells are so diverse. There are approximately 200 types of cells with a variety of anatomy and functions, while we have the same DNA in every cell.
So how does the DNA of each cell know that it wants to make that particular cell and not the other?
How does he know that we want a "liver" here, a "lung" there, and a "bladder" there?
This has to do with what we call gene expression, which is simply the process of converting that information loaded into our DNA into proteins and then into the actual cells that make up our bodies.
But this is done selectively, through a group of chemical tags that can bind to DNA to activate or inhibit one gene at the expense of another.
For example, when we want to make a “liver”, the concentration of those chemical markers responsible for activating the pieces of DNA that make liver cells will be high in those cells specifically that are supposed to make a liver. Those chemical markers opened the door to a new science that we call epigenetic science or Epigenetics, which studies the effects of these chemical markers on our genes.
The effect of these different chemical marks on the same DNA is similar to writing the same sentence with different punctuation marks.
A well-known story on social media says that a judge sentenced a man to death, and sent him to the police with a sign around his neck that reads: "Pardoning him is impossible. He is transferred to prison and executed." But the man on the way to the police managed somehow to change the punctuation marks in the sentence, so they became: "Pardon him. Impossible. Transfer him to prison and execute him."
Delighted to share with you our latest paper.
Here, we test the hypothesis that aging may be driven by DNA damage-induced changes to the epigenome.
Might be due to a glitch in the software of the body that causes it to malfunction, which can be fixed with a reboot? 👇 1/ pic.twitter.com/HYmIbidO1v
— David Sinclair (@davidasinclair) January 12, 2023
Aging... a hypothesis for information
However, there are already problems facing the aging hypothesis through the accumulation of mutations, for example, that the rate of mutations in the case of aging may be lower at times, and there is no clear direct proportion between the pathological symptoms of aging and the rates of mutations within the body.
Here appears Sinclair's hypothesis, which he confirms with his most recent study (and his previous work as well). Our genetic content, this book that contains the codes for the work of all our cells, does not change, it remains the same, but what is disturbed with time are those chemical signs.
This is where a completely new possibility emerges that differs from the aging hypothesis due to mutations, because these chemical markers are easier to manipulate.
At that point, we can look at the matter from a different angle, and it is an informational vision derived from an idea pioneered by the American mathematician, Claude Shannon, and one of the most important founders of information theory in the thirties of the last century, as Shannon was interested in the chaos that occurred during the transmission of radio messages from one region to another. Because those messages do not reach their place every time, and this affects communication between ships and planes, especially in a military field.
In response to this problem, our friend developed a system that controls the communication between the "sender" and the "receiver" by adding an intermediary factor, the "observer", who monitors the signal, obtains a copy of it, and re-transmits it if it does not reach the receiver.
Currently, the protocol that runs the entire Internet relies on that protocol, which is why you're originally reading this now (what we now know as "TCP/IP").
Sinclair and his team ask Shannon's own question: If there was a signal intact in our childhood, but over time it deteriorates and causes aging, could our bodies have a backup copy of it that still contains the essential information from the chemical markers that bind to DNA?
The man's answer is that it exists, and it can be restored. Here Sinclair gives an example: If your copy of "Windows" is damaged, this will not make you terrified, such as if there is a failure in the computer's processor, random access memory (RAM) or hard drive, because you can Any time you run the backup and restore Windows to its original state, in this approach, the error in the copy of Windows is a genetic error, while the error in the computer itself is a genetic error. Fortunately, aging, according to Sinclair, is not a damage in the latter, but in the first .
Yamanaka factors that turn the clock back
Well, now we can talk about the findings of the new study, where the team was able to develop a way to reboot the backup copy of the 'epigenetic' instructions, thereby removing the erratic signals that set cells on the path to aging.
The experiments started by inserting breaks in the DNA of young mice at 20 locations (as we set the example with punctuation marks a short while ago). aging trend.
Within a few weeks, she was already beginning to show signs of aging, not only in her hair starting to turn gray or skin that had wrinkles, but also in her metabolism and body systems.
The mice are now ready to go, as they have become old, and Sinclair and his team have to work on the backup, in the form of gene therapy that causes cells to reprogram themselves, and to turn on the epigenetic markers that identify them.
This gene therapy, which was given to mice, was based on the so-called "Yamanaka stem cell factors", a group of 4 genes discovered by Japanese Shinya Yamanaka and for which he was awarded the Nobel Prize in Medicine in 2006.
These factors can turn the clock back on adult cells, turning them back into “embryonic stem cells” ready to differentiate again. They are the same cells that were found in embryos before their bodies developed over time, and epigenetic factors begin their work. They have to become organs, from the liver, lung, spleen and brain.
But you certainly don't want to reverse the direction of the cells in these mice to go back to zero, you will die immediately, no doubt, but the idea of Sinclair and his colleagues was not to erase the epigenetic history of the cells completely, but to restart it enough to reach the original version.
With much experimentation over the past decade, this team has found that using 3 of the 4 factors causes the cellular clock to rotate back by 57%, enough to make mice young again!
Will we witness the reversal of aging soon?
(Shutterstock)
Well, at that point in particular we must pause a little to look at the other side. What Sinclair and his team accomplished was only a step to prove the validity of a new theory, but scientists are not completely sure of its validity. For example, did the mice affected change immediately after adding Those breaks in their DNA is aging, or is it an aging-like symptom?
This is an important question, no doubt, because basically we can't very accurately, at the functional and molecular level, define aging, and so this calls into question the new theory of aging.
Besides, scientists in this field do not fully understand the implications of using Yamanaka agents, it is expected that there may be harmful effects at the cellular level after applying them on a larger scale, and the matter needs to be studied in more depth and under different experimental contexts In addition, the results of studies in this field, even if they are substantial, the cases of improvement were moderate, and the cells did not return to their backup copy by 100%.
This does not mean that this type of research will stop at some point, but what will happen is the opposite often, but it is a necessary rectification to clarify that we need more time and study to reach at some point a better version of this type of revolutionary treatment, which can be applied in the future to humans.
Sinclair agrees with that idea as well, but notes that real uses of this new knowledge may begin within years to treat some diseases.
But it remains that this theory will undoubtedly change the way we look at the aging process, and the idea that the body can remember how to regenerate and become young again by returning to its backup copy will remain amazing, pushing more scientists day after day to enter this range.
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Sources:
1- Loss of epigenetic information as a cause of mammalian aging
2- Lifespan: Why We Age―and Why We Don't Have To, 2019 – David A. Sinclair, Matthew D. LaPlante)