Future longevity

Everything that kills us. Humanity is on the verge of unraveling the secret of longevity, which it has been working on for centuries — excerpt from the book

Peter Diamandis and Steven Kotler have been researching modern technologies and their development for many years, and with it, transformations that bring progress with them. They outlined all their knowledge and forecasts about the near future in the book "The future is closer than it seems." How technology is changing business, industry and our lives.

In it, the authors predict how the main areas of our life will change over the next 10 years, in particular, transport and movement, retail, advertising, education, healthcare, entertainment, food and finance. NV publishes (translated into Russian — VM) an excerpt from the book "Maybutne near, nezh zdaetsya. Yak technologii zminyuut biznes, promislovist i our life", published by the Laboratory publishing house, which is dedicated to the future of longevity.

The Nine Horsemen of our Apocalypse

We have already said that by extending the duration of a healthy human life, we will significantly accelerate the pace of change in our world. Everything is as simple as possible: the longer a person lives, the longer he works at the peak of his capabilities and, accordingly, makes a significant contribution to innovation. That's just until now we haven't stopped in detail about how to make this a reality. Having considered innovations in the field of healthcare in the previous chapter, it would be logical to focus on the problem of longevity and understand the twists and turns of the race between technology and death.

Let's start, in fact, with our biological clock, known as aging. "Aging is not just a run of the system," explains researcher and head of the National Institutes of Health Francis Collins. — This is a programmed process. Evolution has made sure that some biological species do not live forever. The older generation should free up space for the younger one so that he has enough resources."

To do this, evolution has invented an uninterrupted mechanism known as aging. Scientists identify nine main causes of this decline, the nine horsemen of our inner apocalypse. The remaining sections will be devoted to attempts to overcome them. However, first you need to get to know these riders better and find out the answer to the key question: what is killing us?

1. Genome instability. DNA is not always duplicated according to plan. As a rule, errors in gene expression are fixed and corrected, but not always. Over time, these misfires accumulate and lead to the wear of our body. So, genetic instability harms us and shortens life expectancy. It's like a broken copier, only instead of unreadable documents, the wrong genes "print" diseases like cancer, muscular dystrophy and amyotrophic lateral sclerosis.

2. Telomere reduction. Inside the cell, DNA forms filamentous structures called chromosomes. Chromosomes have telomeres or short DNA fragments at the ends, which are duplicated a thousand times. These repetitions, like bumpers on cars, are designed to protect the nucleus of the chromosome. But when DNA is duplicated, telomeres become shorter. At a certain stage, the cell stops dividing, and we become less protected from diseases.

3. Epigenetic changes. The external world influences the internal one. During life, environmental factors can influence our genes, sometimes not in the best way. For example, contacts with carcinogens can blunt the gene that inhibits the development of tumors. Then the cells begin to grow uncontrollably, and as a result, cancer develops.

4. Loss of proteostasis. Inside the cell, proteins make the weather. They transport "materials", send signals, turn on and off various processes and maintain the structure of the cell. But over time, proteins lose their effectiveness, so the body recycles them. Unfortunately, over the years we sometimes lose this ability to proteostasis. The cellular scavenger is on strike, and we are suffering from a toxic dump of proteins, which can cause, for example, Alzheimer's disease.

5. Nutrient recognition failure. The human body needs more than 40 different nutrients to be healthy. In order for everything to work properly, cells must be able to recognize and process them. But with age we lose this ability. For example, one of the reasons for weight gain is that over the years our body no longer digests fat properly. And this in turn affects the production of insulin and can lead to diabetes.

6. Mitochondrial dysfunction. Mitochondria are such power plants. By converting oxygen and food into energy, they give our cells "fuel". But over time, their productivity drops. As a result, free radicals appear — a harmful form of oxygen that cripples DNA and proteins and causes many chronic diseases associated with aging.

7. Cellular aging. Under the influence of stress factors, cells periodically "age". At the same time, they simultaneously lose the ability to divide and die. These "zombie cells" cannot be removed from the body. They accumulate, infect neighboring cells and cause a real zombie apocalypse, weakening our defenses against inflammation.

8. Depletion of stem cells. With age, our stock of stem cells is reduced, sometimes by tens of thousands of times. Worse, those who remain become much less active. This means that the internal tissue and organ renewal system cannot do its job.

9. Changes in intercellular communication. In order for the body to work properly, there must be a connection between the cells. "Messages" are transmitted through the blood, immune and endocrine systems. Over time, the signals weaken. Some cells don't match, and some turn into zombies. The inflammations caused by them block further communication. Thus, messages do not reach the addressee, and the immune system cannot detect pathogens.

And now that we know what's killing us, let's find out what can save us.

The cosmic speed of longevity

Do you want to receive a Nobel Prize? Explore the worms. And not any, but round nematodes, also known as Caenorhabditis elegans or C. elegans.

This worm has many friends.

Six scientists have already received "Swedish gold" for working with these creatures. As a result, C. elegans became the first organism whose genome has been fully decoded and the structure of its nervous system fully described. However, despite such outstanding achievements, many believe that the greatest contribution of nematodes to science is yet to come, because C.elegans is the first animal to come together in a duel with death and win.

In a Petri dish, C.elegans lives for about 20 days. In 2014, scientists at the National Institute of Health decided to extend this period. Previous studies have shown that this can be done in two ways. If you remove the rsks-1 gene, the lifespan will last for 6 days, and if you get rid of daf-2, then for 20. But these scientists were wondering what would happen if they "knocked out" both genes.

"Scientists have suggested that such mutants should live for about 45 days," wrote Francis Collins, director of the National Institutes of Health, who funded the research. — However, to their surprise, some of these creatures were still alive after 100 days. An incredible increase in the lifespan of worms by 5 times. It's the equivalent of a 400-year-old man."

To apply this technique on a person is exactly what scientists who study the topic of longevity want. Of course, genetics plays a huge role here. Since the first work on C. elegans, other scientists have identified more than 50 genes associated with aging. Five of them seem particularly interesting. If you remove any of them, the life expectancy will increase by 20%.

But it's not just about genetics. Martina Rotblatt's mission to provide humanity with an endless supply of "spare parts" is also extremely important. As well as the availability of surgery, which will be provided by robots, and the development of a new drug, which is engaged in artificial intelligence and quantum computers. At the same time, there is no need to focus on one thing. Only the combination of all these approaches will lead us to a qualitatively new path.

The old way led us to a life of 35 years. This was the case from the Paleolithic era until the end of the Industrial Revolution. In the twentieth century, miracles such as antibiotics, sanitation and clean water allowed us to live longer. In 1950, the average life expectancy was 48 years, and in 2014 — 72. Today Ray Kurzweil and the expert in this field Aubrey de Gray started talking about "the speed of avoiding old age." They say that soon science will learn to prolong our life by one year in relation to everyone already lived. In other words, if we cross this threshold, we will literally be one step ahead of death.

Kurzweil believes that 12 years remain before this threshold, and Gray thinks that 30. Why should we believe them? One obvious fact: you can't take anything with you to the grave. All the money in the world has no meaning. So how much are rich people willing to pay for a couple of extra decades of healthy life? A lot. This explains the growth of investments in the development of anti-aging technologies. One of the most striking examples is Google's Calico company. And, most importantly, although prolonging the life of the elite is a dubious goal, as we have seen, over time, thanks to the merger of technologies, innovations are demonetized and democratized. This means that perhaps you and almost certainly your children will be able to live for decades longer.

Let's look at some of the most promising technologies in this area.

A cure for old age

Easter Island is a far exotic land of strange rumors, stone heads and strange rumors about stone heads. Some say that the elders of the island with the help of special spells can revive these heads and control them like a giant stone army. The rest say that the heads affect the vitality of people. They can both take it away and multiply it, giving power to the chosen ones. Eventually, in the mid-1960s, a small group of scientists discovered that the latter hypothesis could be something more than the usual strange rumors.

It all started when the tiny isolated community of Easter Island decided they'd had enough. Down with minuteness and isolation. They wanted to have an airport. Scientists fussed. One of the most environmentally friendly regions of the world is about to lose its purity and environmental friendliness. An international group of scientists was urgently sent there to collect samples of flora, fauna and microorganisms, including — and this is the most important part of our history — from the soil under one of the mysterious stone heads.

In the end, this soil ended up in the hands of a Canadian microbiologist named Suren Segal, who proved that it has magical properties. It kills the fungus. Segal isolated this component and named it rapamycin in honor of the original name of the island — Rapa Nui. Despite the potential of this discovery, Segal ran out of funds for further research, and he put the drug in a back drawer, where it successfully lay until the end of the 1970s, until a new wave of funding came. Repeated analysis revealed an even greater content of magic in this soil. Rapamycin was not just an antifungal agent. It inhibited the immune system, which created new opportunities for organ transplantation.

This potential has turned into an entire industry. Since then, rapamycin has been used for everything from heart surgery to preventing rejection of transplanted kidneys. And then the researchers made an even more impressive discovery regarding the magic soil: rapamycin inhibits the development of cancer.

The component blocks a protein that promotes cell division. If you give it to worms, flies or fungi, the result will not only contain cancer, but also prolong life. Then the following question arose: will this magic work on mammals?

In 2009, the National Institutes of Health gave an answer to it, demonstrating that rapamycin prolongs the life of mice by 16%. In 2014, all these discoveries led Novartis to decide to conduct tests on humans. This was the first official anti-aging drug trial conducted by a pharmaceutical company. However, when scientists realized that there really was something extraordinary in this soil, they began searching for other components to combat aging.

One of the results of these searches was the discovery of a drug called metformin. This is the most common remedy for diabetes in the world. It slows down sugar production and regulates insulin levels. It also slows down the rate of "combustion" of cells, protects the body from oxidative stress, resists cancer and, as we recently learned, significantly increases the life expectancy of worms, mice and rats. What about people? This question is still open, but scientists are trying to find an answer to it.

While rapamycin and metformin protect us from the destructive effects of age, other researchers are looking for components that will turn back time. We are talking about the so—called senolytic therapy - treatment with drugs that destroy zombie cells that cause inflammation. These cells are called one of the main causes of aging. Now half a dozen companies are developing drugs that destroy zombie cells, thus treating various diseases: from ordinary weakness and osteoporosis to cardiovascular and neurological disorders.

One of the most interesting such companies was Unity Biotechnology, which is developing not least thanks to the investments of Jeff Bezos, Paul Allen and Peter Thiel. The company's scientists have come up with a way to identify and kill senolytic cells. At least it works on mice. But it really works. The result of senolytic therapy performed on middle-aged mice was an increase in their life expectancy by 35%, as well as a significant improvement in their health. All the typical symptoms of aging, from lack of energy to cataracts and kidney failure, either do not appear at all, or occur much later. Unity is developing about a dozen drugs for many diseases caused by aging. Some have even passed the first phase of human testing. A strong player in the field of anti-aging.

And then there is Samumed, another active company dealing with longevity issues. It is a $12 billion enterprise based in San Diego, focused on the so-called Wnt signaling pathways. As the name suggests, this is the mechanism by which the body transmits its messages. In this case, these messages control a group of genes that simultaneously help the human embryo grow and play an essential role in the aging process. Failures in the Wnt signaling pathways are directly associated with 20 diseases, including cancer. Therefore, almost every major pharmaceutical company has been studying this issue for a long time. But Samumed may have managed to find the answer.

They focused their efforts on one specific Wnt signaling pathway regulating the behavior of adult stem cells. The company has developed 9 so-called regenerants. All are under the control of the US Food and Drug Administration. This list includes drugs for both hair loss and Alzheimer's disease. However, their success in the fight against arthritis and cancer attracted the most attention.

Let's start with arthritis, which affects 350 million people worldwide. There are no drugs for this disease yet. But in 2017, Samumed published the results of a small study on knee osteoarthritis. As part of the trials, 61 patients received a knee injection of a drug to balance Wnt. As a result, all participants noted a significant improvement. Repeated examination 6 months later revealed a significant reduction in pain, improved mobility in the joint, as well as an average build-up of almost 2 mm of new cartilage.

"The active substance stays in the body for six months," explains Osman Kibar, CEO of Samumed. "During this period, it forces stem cells to grow new cartilage tissues — as strong and elastic as a teenager's. The fact is that there are progenitor stem cells in the body of even an 80-year-old person, they just need to be given the right signal." But maybe this is just the beginning.

"Injecting the same active substance into the spine of rats with damaged intervertebral discs restores the entire disc," says Kibar. "If you look at the quality of the cells, this disc is younger and stronger."

However, the human body is a slightly different story. Very few drugs are moving from testing on mice to testing on humans, but some Samumed drugs that treat injuries to the shoulder girdle and Achilles tendon muscles have already passed the first phase of testing. And the knee arthritis drug is already going through the third. There is still a lot of work ahead, but as a result, we can get a drug that will give people a few extra decades of healthy mobility.

An equally fascinating part of Samumed's research is related to cancer. In fact, cancer occurs when there is a malfunction in the work of stem cells. By blocking the signaling channels that lead to this, Samumed drugs take aim at all types of tumors. Most of these drugs are still undergoing clinical trials or the first stages of testing for safety and efficacy, but within the framework of charity testing programs, Samumed allowed them to be given to terminally ill patients. And the results were brilliant.

Within one experimental group, thanks to a small regular dose of the drug, the growth rate of tumors was slowed down by 80%. During another study, which involved patients with pancreatic cancer, long-term use of the drug managed to contain this usually fatal ailment. "No medicine helped this woman," says Kibar about one patient. — She weighed about 30 kg, and doctors sent her home to die. And now, after a year of using our drug, she is normal. She travels, goes on a date, weighs 54 kg and lives a normal life. Of course, these are only the first successes in this direction, but the beginning is very promising."

The Bloody Fountain of Youth

In the early 2000s, a group of Stanford researchers began to look for the source of youth in an unexpected area: in the legends of Dracula. Similar stories existed in ancient Greece, were mentioned in Ovid's poetry, and then transformed into Gothic stories about vampires, in which we are talking about the rejuvenating effect of young blood. Stanford scientists decided to test this theory on mice.

Reproducing the terrible ancient technique of parabiosis, they connected the cardiovascular system of young and old mice and began to drive the blood of the first through the body of the second. The result was visible to the naked eye. The young blood actually revived the older individual.

But that's not all. Some tissues and organs of an old animal have adopted the properties of a young and healthy one. Further studies have confirmed and shown that the process also works in the opposite direction. If you drive the old woman's blood through the body of a young animal, her biological clock will run forward.

This work aroused great interest. Over time, scientists began to understand why such rejuvenation occurs. The team from Harvard has found that young blood promotes the formation of new neurons in the brain and stops the thickening of the walls of the heart, accelerating aging. Also, these scientists have discovered a substance known as "growth/differentiation factor 11" or GDF11, which is behind at least several of these processes.

In 2014, another group of researchers proved that injections of GDF11 make mice stronger, improve their memory and blood supply to the brain. Other studies have demonstrated that GDF11 has a positive effect on the cardiovascular system, accelerates muscle recovery, increases endurance and improves brain function.

All these efforts have attracted the attention of business. For example, the Elevian company, led by Dr. Mark Allen and a quartet of Harvard regenerative biology specialists, is also looking for the secrets of longevity in GDF11 and other aging-slowing substances. Meanwhile, Alkahest is working on developing a plasma mixture for the treatment of Alzheimer's disease.

Wired magazine called it "finding a needle in a haystack," because blood plasma contains more than 10 thousand different proteins. But in fact, it's more like looking for a needle in a pile of gold. The search for rejuvenating proteins has led to a real biological "gold rush". Startups work hard, not to mention pharmaceutical giants. In 2017, the National Institute for Research on Aging allocated $2.35 billion to scientists engaged in such research. So in the XXI century, not only flying cars and robots are real, but also Count Dracula.

For thousands of years we have been searching for the source of youth. All the above—mentioned studies show that the subject of our searches is more time than place. The Fountain of Youth is a specific period of history when technology challenges mortality. Yes, the question of whether we will ever live forever is still open. But the transformation of a hundred—year-old man into a sixty-year-old is already a matter of time.

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