18 May 2021

How to look for a pill for old age

"We have discovered a drug that prolongs life by 25%"

Plus One

Scientists and experts are looking for ways out of the global climate crisis, one of them is the former top manager of RAO UES of Russia and the president of the company Longevica, Alexander Chikunov. He told me Plus-one.ru why the problem cannot be solved by the efforts of individual countries, as well as about their experiments to find life-prolonging drugs.


Experiments with the mortality curve

– You have been engaged in energy for almost six years and suddenly switched to finding a cure for old age. Why?

– Apparently, a genetic predisposition started talking in me (laughs): my mother was a pediatrician, and my grandmother was a Siberian healer. But seriously, after the reform of the Russian electric power industry was completed, there was a choice of what to do next. I was 45 years old, and I was at the peak of my career. Then I asked myself important questions: "Who am I? Why do I live? Can I create something important, useful for humanity?" After six months of studying global trends – from artificial intelligence to solar panels – I stopped on the topic of aging and the search for a cure for it. I was impressed by the scale of the task, and I was ready to spend several million dollars on it.

– An enthusiastic neophyte with a large amount of money in his pocket: weren't you afraid that you might invest in a failed project?

- no. I met Academician of the Russian Academy of Sciences Vladimir Petrovich Skulachev, who has been studying the issues of aging since the 1990s. His research was funded by Oleg Deripaska until 2008, but stopped due to the economic crisis. I came to Vladimir Petrovich's laboratory, he told me about the antioxidants he was working on, and I decided to support his developments. Every week Vladimir Petrovich lectured me about aging.

In 2009, I organized a seminar in Moscow, where I gathered scientists working on the same problem. So I met with a professor at Rutgers University (New Jersey, USA) Alexey Ryazanov. Alexey suggested taking mice and testing all pharmacological preparations known to man on them – about 10 thousand officially registered names. Thus, it is possible to identify drugs that shift the so-called mortality/survival curve, characteristic of any population, to the right, that is, increase life expectancy. And then to unravel the mechanisms – how exactly they did it. I was so impressed with this idea that I immediately agreed to finance it.

– How much did these experiments cost you?

– It turned out that to test 10 thousand drugs, you need about $ 100 million. I didn't have that kind of money, so I had to reduce the number of medications to 1,040 substances. The volume of investments decreased to $7 million. We signed a contract with the American The Jackson Laboratory.

– Tell us about the essence of the experiments.

– We called our experiment "Screening-1". A huge number (20 thousand) of long-lived female mice were divided into cohorts of 15 animals. One cohort – one drug. All mice of each group received one substance dissolved in water every day during their entire life from the beginning of the study. During the experiment, we wanted to find a drug that would shift the curve to the right by 20-30%. At the time when we conceived the experiment, it was known that calorie restriction prolongs the life of mice by 25%. Nothing else had such a significant effect. In July 2009, after the start of our experiment, the first publication was published about rapamycin (an immunosuppressant used in organ transplantation. – Approx. Plus-one.ru ) is the first drug with the proven effect of increasing life expectancy in long–lived mice. Experiments have shown that rapamycin extended the life of experimental animals by 12-14%.

After a year of our experiment, the budget increased by another $3 million. It turned out that the laboratory experts initially assumed that 30% of mice would die in the first year due to the toxicity of the drugs, but this did not happen.

– Were you ready for such a turn of events?

– No, but I decided to go all the way. We completed the experiment in mid-2013 and received 1,033 graphs (according to the number of mouse cohorts that reached the end), of which about 60 curves shifted towards an increase in life expectancy. However, no substance gave more than 25%. Approximately 30-40 substances demonstrated a shift to the left: the strongest of them reduced life by 20%. It was also interesting that not so many substances worked in the direction of reduction. In the remaining 900 schedules, the deviations were insignificant, that is, the drugs did not affect life expectancy in any way. We began to analyze substances that showed a shift towards increasing life, but they were all completely different.

– On what principle did you select the substances?

– Alexey Ryazanov suggested grouping substances by pharmacological classes (antibiotics, antiparasitic, antihistamines, and so on) and already looking at the correlation of life extension according to them. We collected 62 classes, and only two showed a correlation with life extension. Also, out of 1,033 substances, only five – Inulin, Pentetic Acid, Clofibrate, Proscillaridin A, D-Valine – showed an individually statistically significant effect of increasing life by 16-22%. Previously, only one drug in history has demonstrated similar results – the already mentioned rapamycin. In 2015, we moved from the substances themselves to the mechanisms of their action and began to "dig" in this direction – to study two selected classes.

– What are these mechanisms?

– Over the years, we have tested many different hypotheses. In 2020, we realized that the mechanisms of life extension that we discovered were directly related to food. Every day we take harmful substances with food – so-called toxins of a special kind. The detoxification system created by evolution – the kidneys and liver - is responsible for fighting them in the body of any living being. This system works 24 hours a day, but from the middle of life its efficiency decreases. As a result, harmful substances accumulate, causing multiple chronic inflammations and age-related diseases. It turned out that the operation of this system can be "improved" with the help of certain substances. For example, Inulin is a prebiotic that restores the gastrointestinal microbiome. The beneficial bacteria that he feeds produce metabolites that activate the detoxification system, which leads to the prolongation of life.

– How do you plan to monetize your discoveries?

– Now we are creating a set of dietary supplements from those substances that are safe, well-known and have shown a shift of the curve to the right. Let's start selling them with China, as one of the biggest markets. We will attract investors. We also plan to make "clean" food. Soils have been actively treated with fertilizers in recent decades. We know exactly which toxins in food shorten life, and we will strive to clean the soil and our products from them. In parallel, we will launch the development of one or more drugs against specific age-related diseases based on the mechanisms we have discovered.

Why electric cars won't save you from an environmental disaster

– You have been studying the topic of a possible global catastrophe of human civilization for many years. How much time do we have left to solve the accumulated problems?

– We have long entered the era of catastrophe. In the next 10 years, we need to radically change our habits – close coal-fired power plants, find a replacement for nitrogen fertilizers or figure out how to double the harvest without fertilizers. But this is unrealistic. This means that we will continue to move "along bad trajectories."

Unfortunately, we are fixated on, relatively speaking, "electric vehicles", which do not solve the climate problem as a whole. We need to think globally, to become one humanity. At the level of individual countries, as today, we will not solve the problems of the XXI century. In the near future, I want to create a new think tank where visionaries and world-class experts will look for a way out of this situation.

– Who can you call a visionary who can offer a way out of this crisis?

– For example, the Czech-Canadian scientist Vaclav Smil. I suggested translating two of his books into Russian in 2011. He is one of my gurus. People who grew up at his works cannot say that electric cars and "green" hydrogen will save humanity from an environmental catastrophe, as those who today occupy 90% of the public ether say. But in reality, we all have a difficult job ahead of us, because there are almost no positive scenarios for the XXI century.

Alexander Chikunov was born in Krasnoyarsk in 1963. From 2002 to 2008 he worked at RAO UES of Russia: he was a member of the management board and managing director of the energy holding. In 2009, he created the company Longevica, which is engaged in finding solutions to increase human life expectancy and prevent the development of age-dependent diseases. In 2011, he became one of the founders of the Institute of World Ideas, whose goal is to create a long–term vision of human development. In 2020, he launched the 4Waves project.

Apply for participation in the "Change Management. Visionaries" is available until July 2, 2021 on the event's website.

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