Three theories of aging and ways to beat it

Excerpt from the book of the science pop star Michio Kaku

Alpina Non-fiction Publishing house publishes a new book by theoretical physicist and popularizer of science Michio Kaku.

TASS publishes an excerpt about how scientists hope to stop aging.

In the science pop, the American Michio Kaku occupies a place next to Stephen Hawking and Richard Dawkins, that is, somewhere at the very top. Each of his books is an event. While Kaku was still engaged in science, and not only its popularization, he climbed into the very wilds: string theory and other areas on the border of physics and fantasy with a sophisticated mathematical apparatus. His texts for readers without special training are sustained in the same spirit: it is not immediately clear where science ends and science fiction begins in them. But that's what they are good for.

In the "Future of humanity: Colonization of Mars, traveling to the stars and gaining immortality" Kaku conducts an audit of the latest knowledge and tries to imagine what this knowledge will allow us to do. His prognosis is optimistic. A settlement on Mars? It is possible, but what if we fly to other stars? Kaku believes that truly great achievements await humanity ahead.

In this he is old-fashioned. The same enthusiasm was possessed by the most prominent minds of the modern era, who believed in endless progress, in the fact that nature can be fully cognized and subdued. Like scientists of the past, Kaku is not very interested in whether it is necessary to do this and what is the downside of progress. But the XX century, when people were sterilized and exterminated according to the scientific postulates of eugenics, and the world almost burned down in the flames of nuclear bombs, showed that knowledge does not always bring good.

In the above excerpt from Kaku's new book, we are talking about how to improve a person for traveling to other star systems. Scientists will have to try: even to the nearest star will have to fly hundreds, or even thousands of years.

Can modern science reveal the secrets of aging processes by slowing down or even stopping the biological clock altogether and increasing life expectancy almost indefinitely?

Humanity has been striving for this since time immemorial, but there is also a new factor – currently this idea has attracted the attention of many of the richest people on the planet. More and more Silicon Valley entrepreneurs are investing millions in the study of aging processes in order to defeat this process. Not satisfied with uniting the whole world into a single network, they set themselves a new goal – to live forever. Google co-founder Sergey Brin hopes to find nothing less than a "cure for death." And the company Calico under Brin's management may eventually pour billions of dollars into a partnership with the pharmaceutical company AbbVie to deal with this problem. Oracle co-founder Larry Ellison believes that coming to terms with human mortality is "unthinkable." PayPal co-founder Peter Thiel dreams of living a modest 120 years, while Russian Internet magnate Dmitry Itskov wants to live up to 10,000 years. With the support of people like Brin and access to technological innovations, we may finally be able to channel the full power of modern science to unravel this ancient mystery and increase our life expectancy.

Not so long ago, scientists revealed one of the deepest secrets of the aging process. After many centuries of false starts, we have only a few reliable, testable theories that seem promising. Among them are calorie restriction, telomerase and aging genes.

Of the above, only one method has already proven the ability to prolong the life of animals, sometimes even double its duration. This method implies a serious restriction of the caloric content of the animal's food.

On average, those animals that eat 30% fewer calories live 30% longer. This has been demonstrated on yeast cells, worms, insects, mice and rats, dogs and cats, and now on primates. Strictly speaking, this is the only method accepted by all scientists: everyone recognizes that it changes the life expectancy of all animals, without exception, on which tests have been carried out so far. The only significant animal on which this method has not yet been tested is a human.

The theory is that animals in the wild lead a half-starved life. In fat times, they use their limited resources to prolong the race, and in lean times they enter a state close to suspended animation in order to save resources and survive the hungry period. Reducing the diet triggers the second variant of the biological response of the body, and the animal lives longer.

The only problem with calorie restriction, however, is that with a low-calorie diet, animals become sleepy, sluggish and lose interest in sex. And most people will balk if you offer them to eat 30% fewer calories. Therefore, the pharmaceutical industry would very much like to find chemicals that control this process and master the power of calorie restriction, while avoiding its obvious side effects.

Not so long ago, a promising chemical called resveratrol was isolated. This substance, found in red wine, helps activate the sirtuin protein, which has been shown to slow down the oxidation process – a fundamentally important component of aging – and therefore can partially protect the body from aging-related damage to molecules.

I happened to interview Leonard Garente, a researcher at the Massachusetts Institute of Technology, who was the first to demonstrate the connection between these chemicals and the aging process. He was surprised by the number of fanatics of new diets who attacked these compounds as a source of eternal youth. Garente was skeptical about this, but admitted that if a real cure for aging is ever found, then these substances may play a role here. He even became one of the founders of the company Elysium Health, engaged in such research.

Another key to the problem of aging may be telomerase, which helps regulate the course of our biological clock. With each cell division, the ends of the chromosomes, called telomeres, become slightly shorter. Over time, after about 50-60 divisions, telomeres become so short that they disappear altogether, and the chromosome begins to fall apart. As a result, the cell becomes decrepit and loses the ability to function normally. There is a limit for the number of cell divisions, called the Hayflick limit. (I once interviewed Dr. Leonard Hayflick, and he laughed when I asked him if there was any way to circumvent the Hayflick limit and protect yourself from death. He was highly skeptical and considered this biological limit to be the main one in the complex and diverse biochemical process of aging. We don't know much about it yet and are far from being able to change this limit in the cells of the human body.)

Nobel laureate Elizabeth Blackburn is more optimistic: "All signs, including genetics, say that there is a causal relationship between telomeres and those unpleasant things that happen as you age." She notes that there is a direct link between shortened telomeres and some diseases. For example, if your telomeres are shortened (as in the lower third of the population), the risk of developing cardiovascular diseases is 40% higher for you. "It is the shortening of telomeres, apparently, that underlies the risk of those diseases that kill us... these are heart disease, diabetes, cancer, even Alzheimer's disease," Blackburn concludes.

Recently, scientists have been experimenting with telomerase, an enzyme discovered by Blackburn and her colleagues that prevents telomere shortening. This enzyme is able, in a certain sense, to "stop the clock". Skin cells washed by telomerase can divide indefinitely, going far beyond the Hayflick limit. I once interviewed Dr. Michael West, who worked at Geron Corporation. West experiments with telomerase and claims that he can "immortalize" a skin cell in the laboratory, so that it will live forever. Skin cells in his laboratory can divide not 50-60, but hundreds of times.

It should be pointed out, however, that telomerase should be handled very carefully, since cancer cells are also immortal and also use telomerase to achieve immortality. One of the differences between cancer cells and normal ones is that they live forever and multiply without any limit, giving rise to tumors that kill us. So an undesirable by-product of using telomerase can be cancer.

Genetics of aging

Another opportunity to defeat aging is related to genetic engineering.

The fact that genes strongly influence aging is obvious. Butterflies after leaving the cocoon live only a few days or weeks. Mice that are studied in laboratories usually live only about two years. Dogs age about seven times faster than humans and live a little more than ten years.

Studying the animal kingdom, we find creatures that live so long that their life expectancy is difficult to measure. In 2016, the author of an article in the journal Science reported that the Greenland polar shark lives on average 272 years and exceeds the life expectancy of the bowhead whale (on average 200 years). This makes the Greenland shark the longest-lived vertebrate animal. Scientists calculated their age by analyzing the layers of tissue in the shark's eye, which grows in layers like an onion. Moreover, they found one shark, which was 392 years old, and another, which may have been as much as 512 years old.

Thus, different biological species with different genetic apparatus differ greatly among themselves in life expectancy. Studies show that even among humans, although our genes are almost identical, twins and close relatives in general have a close life expectancy and that people selected randomly differ much more on this basis.

But if aging is at least partly controlled by genes, it is very important to identify the genes that control it. Several approaches are possible here.

One promising approach is to analyze the genes of young people and then compare them with the genes of old people. By comparing two sets of genes using a computer, you can quickly identify the places where the most genetic damage caused by aging is observed.

For example, the aging of the car occurs primarily in the engine, where corrosion and mechanical wear are most affected. In a living cell, the role of the "engine" is played by mitochondria. It is in them that sugars are oxidized with the release of energy. A detailed analysis of the DNA inside the mitochondria indicates that errors, indeed, are concentrated here. It is hoped that someday scientists will be able to use the cell's own repair mechanisms to reverse the process of accumulation of errors in mitochondria and thereby prolong the useful life of the cell.

Thomas Perls of Boston University, based on the assumption that some people are genetically predisposed to a longer life, analyzed the genes of centenarians and described 281 markers for genes that seem to slow down the aging process and somehow make centenarians less vulnerable to diseases.

Little by little, the mechanism of aging becomes clear to us, and many scientists are cautiously optimistic that in the coming decades it may become manageable. Studies show that aging, apparently, is just an accumulation of errors in DNA and cells, and someday we may learn to stop or even reverse this process. Moreover, some Harvard researchers are so optimistic that they have already created commercial companies in the hope of making money on the results of research on aging processes.

The fact that genes play an important role in determining the duration of our life is beyond doubt. The problem is to determine which genes are involved in the process, separating their action from the action of the environment, and change the necessary genes.

Conflicting theories of aging

One of the oldest myths associated with aging says that you can preserve eternal youth if you drink the blood or absorb the soul of the young, as if youth can be transmitted from person to person, as in the legends of vampires. A succubus is a beautiful mythical creature that remains eternally young because it sucks youth out of your body with a kiss.

Modern research shows that this idea may contain a grain of truth. In 1956 Clive McKay from Cornell University connected and stitched the blood vessels of two rats – an old wreck and a young energetic individual. He was amazed to find that after the operation, the old rat began to look younger, and the young one, on the contrary, older.

A few decades later, in 2016, Amy Wagers at Harvard University re-tested the results of this experiment. To her surprise, she found the same rejuvenating effect in mice. After that, she isolated a protein called GDF11, which, apparently, was the basis of this process. Wagers' results were so remarkable that Science magazine named them among the top ten breakthrough discoveries of the year. However, in the following years, other groups of researchers, trying to verify her startling statement and repeat the experiment, received mixed results. It is still unclear whether GDF11 will become an important weapon in our anti-aging campaign.

Another contradictory result is associated with human growth hormone (HRH), which for some time caused almost a craze. Unfortunately, information about the effectiveness of HGH in the fight against aging is based on a very small number of reliable studies. In 2017, the results of a large–scale study at the University of Haifa (Israel) involving more than 800 patients indicated rather the opposite result - in fact, HRH can reduce life expectancy. Moreover, the results of another study show that a gene mutation that causes a reduced level of this hormone may prolong a person's life. This means that taking HGH can cause negative consequences.

The results of these studies are a useful lesson for all of us. Wild statements made about the causes and nature of aging often faded upon closer examination and careful analysis. Today, researchers demand that all research results, without exception, be verifiable, reproducible and refutable, which is a sign of real science.

Almost before our eyes, biogerontology is being born – a science that should reveal the secrets of the aging process. The growth of scientific activity in this area can be called explosive, now many promising genes, proteins, processes and chemicals are being investigated, including the FOXO3 gene, the DNA methylation process, the mTOR protein complex, insulin growth factor, Ras2 genetic modification, acarbose, metformin, alpha-estradiol, etc. Each of these areas of research has aroused great interest scientists, but so far we have only preliminary results. Time will tell which of these approaches promises the best results.

The search for the source of eternal youth – what mystics, charlatans and madmen used to do in the old days – is led by the best scientists in the world. Although there is still no cure for aging, scientists are considering a variety of approaches to the problem, and some of them seem very promising. They can already extend the life span of some animals, but it is unclear whether it will be possible to transfer these techniques to humans.

Research is progressing at an incredible pace, but we are still very far from solving the mystery of aging. Over time, we may be able to find a way to slow down or even stop the aging process by combining several approaches being developed. Perhaps the next generation of scientists will make breakthrough discoveries in this field. Gerald Sussman once lamented: "I don't think the time has come, but it's already close. I am afraid that, unfortunately, I belong to the last generation to die."

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