Today's story is particularly interesting because it touches on a problem that is valid for all of us: the small matter of aging
Many theories have been proposed in the past - and are still being proposed - as a way to explain the phenomenon of aging. In recent years, a new theory has been added to them that explains aging. Apparently, there is nothing new in this, but just last week a fascinating study was published that demonstrated for the first time how aging can be reversed in tissues that have undergone appropriate treatment.
But before we get to the research, we need to first understand the biological basis for the epigenetic aging theory.
In 2013, Prof. Steve Horvath shocked the world of aging research. Here I should add a full disclosure: Steve is a friend I have had the pleasure of working with for the past two years, and he is a great combination of friendliness and uncompromising criticism. In other words, he is the ideal scientist, who accepts and even invites criticism, and uses it to find ways to strengthen his research.
Horvath discovered a new type of aging clock, which was more accurate than any clock that had existed up to that time. His two most relevant aging clocks are called the "Werewath Clock" and GrimAge, and they can determine the 'biological age' of any person.
But, ask now, what does "biological age" mean?
Each of us knows how old he is, according to the date of birth written on the identity card. But we all know healthy XNUMX-year-olds who do not suffer from any old age disease, and alongside them there are also those who already at the age of sixty began to suffer from old age diseases such as Alzheimer's, Parkinson's, cancer, arteriosclerosis and more. Each of these has a different 'biological age'. The healthy XNUMX-year-olds, for example, may have a biological age that is twenty years lower than their chronological age - that is, that measured by the passage of time only. And the patients in their sixties may have a higher biological age, by ten or even twenty years.
The problem is that until Horvath identified his epigenetic clocks, there was no good way to estimate the biological age of humans. There were various ideas for ways of measuring, but none of them were really successful. Horvath's epigenetic clocks, however, can predict a person's chances of developing senile diseases better than any other clock discovered to date—and are even more successful than relying on a person's chronological age. Horvath's epigenetic clocks that are about to revolutionize the study of aging
Horvath's most successful watch, as of today, is the GrimAge watch that was first demonstrated in 2019. Using this watch, you can predict the time to death, the time to cardiovascular disease, the time to the development of the first case of cancer, the time to muscle weakening and mass depletion the bone, cognitive deterioration and even linked to the age of menopause in women[1]. All of these, as mentioned, are predicted by the clock in a better way than relying on the chronological age of the person[2].
The discovery rocked the world of aging research, as it provided for the first time accurate clocks for determining the biological age of humans. And not only that, but Warath went on to demonstrate that the same clocks also work in mice and other animals, and even in monkeys. In other words, it is a universal mechanism for determining biological age.
All of this was impressive in itself, and opened the way for countless inventions to slow down and stop aging, because for the first time we had a clock that determined biological age. Until now, to find a solution to aging, companies had to conduct decades-long studies to see if the proposed material actually works. The result was that no pharmaceutical company even tried to conduct such long trials. But Horvath's clocks could, in theory, show how people's biological age changes following some intervention. In fact, they give us for the first time a way to gauge the success rate of drugs that may slow down aging, through experiments that will last less than a year. Indeed, studies from recent years have shown that it is possible to influence the biological age in humans and reduce it by approximately two years by restoring the functioning of the immune system[3].
This is all well and good, but then Horvath and others raised another question: Is it possible that the clocks he uncovered are not just indicators of biological age, but are themselves responsible for aging? Is it possible to restore the body through a direct effect on the clocks themselves?
The research I want to review today shows that the answer may be yes. If its results are also verified in humans, then it will open the way to restore tissues that have aged, and thus be a kind of fountain of youth that we can all enjoy. But to explain the research and its results, I first need to dive into the biology that explains how Horvath's clocks work.
The full name of the Wervath clocks is "an epigenetic clock based on DNA methylation". I know, scary name, but the explanation is not really that complex.
We know that DNA is found in almost every cell in the body, and provides the cell with the instructions it needs to continue functioning. You can think of DNA as a book, each page of which is a garden. And each such gene, or page, contains instructions for building proteins that do a large part of the actions in the cell.
In genetic engineering, researchers use tiny scissors (not really, but let me be poetic here) to cut entire pages out of the book and replace them with new pages. Or even cut out one word from the page and replace it with another word. But when the cell itself wants to turn off certain genes over time, it uses a different method: it methylates them.
What it means? Simple: certain proteins attach a group of atoms known as "methyl" to the DNA in that region. Then a miraculous thing happens: the DNA strand in that region curls up and folds so that the genes there can no longer influence the actions in the cell. If we stick to the metaphor of the book, then the cell actually glues several pages together, so that the instructions in them cannot be read.
This process - of gluing together columns of DNA - is what explains why embryonic stem cells become more specialized cells, such as muscle cells and nerve cells. Embryonic stem cells begin their lives with a minimum of methylation, and only when the cell 'turns off' certain genes, are they able to mature and become the cells from which the body is built. Such changes in the DNA structure are called "epigenetic changes".
Horvath's epigenetic clocks examine, in fact, the degree of DNA methylation in certain regions. For a reason that is not yet completely clear, it turns out that different methylation levels can reflect biological age.
And now we will return to the original question, but in a more detailed way: Is it possible to directly influence the degree of methylation of the DNA - in fact, to cut off the glued pages so that the cell can read them again - and thus rejuvenate the cells, and accordingly also the whole body?
The new study suggests that this is indeed the case.
The new study was published in Nature - one of the most prestigious scientific magazines. The researchers behind it, of which Horvath is one, wanted to affect the level of methylation in cells artificially. They hoped that in this way, they could make the cells become younger. They deliberately tried to make a minimal change, which would not turn back into embryonic stem cells - which would have caused all the body's cells to separate from each other.
The result, we'll tell you right now, was significant enough for the researchers to confidently state in the article that -
"We have shown here that it is possible to safely reverse age in a complex tissue, and to restore its biological activity in living organisms."[4]
But how did they do it?
The researchers created a virus that injected into the nerve cells of elderly mice (twenty months old) certain factors that affect the level of methylation in the cells. They focused on the nerve cells since almost all animals known to us experience a deterioration in the regenerative capacity of their nerve cells with age. More specifically, they chose to try and restore the optic nerves, which transmit information from the eyes to the brain. In the mice tested, those nerves suffered severe damage... until they went through the process that reduced the level of methylation in the cells. After that, they began to rapidly regenerate over several weeks, similar to the rapid recovery ability that characterizes any young animal.
To clarify the meaning of the discovery: today there is no treatment capable of causing rapid regeneration of the nerve cells after an accident. The researchers demonstrated exactly this feat in elderly mice, just by playing with the level of methylation in their cells.
Well, good and well: we managed to restore at least one tissue in mice. But does the treatment also work in humans?
We do not yet have a clear answer to this, nor will there be until the relevant clinical studies are conducted. But the researchers performed experiments in the laboratory on human nerve cells and discovered that yes - the same factors that succeeded in reducing methylation in the mouse cells, also lead to the same result in human nerve cells in the Petri dish, after they had suffered a severe injury.
But the researchers didn't stop at just renewing the optic nerves. They wanted to test whether the same treatment also helps to deal with glaucoma - the world's leading cause of blindness in the elderly. They performed the same treatment on the eyes of elderly mice, and in this way succeeded in restoring half of the visual acuity of the mice that was lost due to glaucoma. In fact, the researchers were able to restore even the visual acuity of 12-month-old mice in the exact same way.
Indeed, the researchers really showed that they could
"To safely reverse age in complex tissue, and restore its biological activity in living organisms."
The most important significance of the new study is that it provides significant support that Horvath's watches do not merely reflect the aging process, but directly cause it. If this is the case, then it is possible to rejuvenate cells in different tissues in relatively simple ways... at least on a conceptual level. On a technical level, much more research is required - the kind that takes many years - to develop the tools that can safely affect the level of methylation in human cells.
If we discover that the same treatment also affects humans and restores their old tissues, then this will be the beginning of a huge revolution: a way to help the body fight off the damage of aging and extend life significantly. At the very least, such a reversal of the biological age will greatly extend the time until the development of some of the aging diseases that destroy the quality of life of the elderly.
But even if it turns out that all this is nothing but a flower owl, we still know one thing: Horvath's clocks work and have already been tested and verified in dozens of different studies. This means that for the first time we have a good way to estimate the effects of treatments of all kinds on biological age. Until now we have tried to develop treatments to stop aging without being able to really know if they work. We were like basketball players trying to improve their ability to shoot the basket, without knowing whether the ball they threw managed to hit the basket. It is no wonder that the treatments so far have not shown much success in humans.
Now we finally have a way to understand which treatments 'hit the basket'. We can know which treatments affect the biological age and perfect and optimize them even more, in an attempt to slow down, stop, and maybe even reverse the aging process.
We will not see the results of this development in the next five years, and perhaps not even in the current decade. But if you're under sixty, you probably have time. It can be hoped that the more effective treatments that will be developed through Horvath's clock studies will not only slow down the aging process but - as the new research has demonstrated - reverse it and make the patients really young.
So even if you are really elderly - it's worth staying alive for another decade or two. For the first time in human history, there is a real chance that when you reach the end of that period, you will be younger than you started it.
Successfully!
More of the topic in Hayadan:
- The robot that will fix me: nanotechnology in the human body - from Dr.Roey Tsezana's book "The Guide to the Future"
- Stopping Death Chapter 1: The Road to Eternal Life: About aging, and the ways to prevent it
- The fountain of youth? Researchers have discovered a new class of drugs that delay aging and extend active life in mice
[1] https://academic.oup.com/biomedgerontology/advance-article-abstract/doi/10.1093/gerona/glaa286/5992253
[2] https://pubmed.ncbi.nlm.nih.gov/30669119/
[3] https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13028
