Recently we launched a new podcast "The Future We Deserve" . The first issue was dedicated to longevity technologies. And for those who find it more convenient to read rather than listen, we have prepared a story based on the conversation between our guests: Maxim Kholin and Petr Fedichev, co-founders of Gero, which develops drugs for the systemic fight against aging using artificial intelligence.
Why slow down aging?
Pyotr Fedichev graduated from Phystech and continued his scientific research in the Netherlands and Austria in the field of theoretical physics. Since 2004, he moved to biotechnology projects. It soon became apparent to Peter and his colleagues that the problem with modern medicine is not that the pharmaceutical industry cannot match a drug molecule against a specific biological target. And the fact is that biologists and doctors often simply do not know against which proteins, genes and targets a medicine needs to be made in order to cure any disease. Thinking about how to solve this problem with the help of their knowledge and experience, scientists came to the conclusion that the only "disease" that today can be "solved" in terms of physics and mathematics is aging.
Researchers have developed algorithmsanalysis of large biomedical data for the effective search for markers and regulators of aging. Practical tools are proposed that use quantitative models of aging and combine the application of artificial intelligence and physics approaches borrowed from the physics of complex dynamical systems. New hypotheses are tested in laboratory on animals in leading foreign laboratories, and the research results are published in key scientific journals. Researchers have already succeeded in rejuvenating mice with experimental therapy against the target predicted by AI. Funds for this - $ 2.2 million - attracted the Russian-Singaporean company Gero, which specializes in the development of ways to slow down aging using AI.
The idea of developing a drug specifically against aging, and not some kind of disease, is rather unusual for the pharmaceutical and medical industries. Usually, you need to get sick first in order to be treated. And from aging you need to start to heal before you get sick. Until recently it was difficult to raise money for such projects, but now it has become easier to find investors. Populations in many countries are aging. For example, in a few years China will have 250 million people over 60. It is obvious that their work capacity will be limited, they will suffer from a whole bunch of age-related diseases. And due to the fact that in China previously only one child per family was allowed - now this restriction has already been lifted - the situation with the aging of the population will begin to improve only in 20 years. In developed countries, similar problems:if the number of old people increases at the same rate as today, and even against the background of a constant decline in the population, the burden on the pension and medical system will soon become exorbitant.
The main reason for the decline in labor productivity with age is a decrease in neuroplasticity, that is, the ability to learn and relearn. Today, this is required more and more often. Therefore, from a certain age, people become illiquid in the labor market, no one wants to hire them. We need to help them maintain their physical and cognitive abilities at their peak for as long as possible, this will have a huge economic effect. This problem is worth tens of trillions of dollars. And to solve it, an industry is actually being created whose task is to try to slow down aging and help people maintain their productivity, earn at least for themselves for the longest time possible. The baby boomer generation that is now starting to die en masse is the richest generation in the history of civilization. These people control and manage tens of trillions of dollars.Therefore, the creators of technological solutions that can somehow increase the quality of life of baby boomers will receive the most grateful audience and will be able to earn a lot of money.
Naked mole rats
Today, many companies, including tech giants, are actively investing in anti-aging technologies. Google created Calico, which has experimented with 6,000 naked mole rats, small burrowing rodents that live underground. They are slightly larger than a mouse, but if mice live 1.5 years, then naked mole rats - about 30, and throughout their life they do not observe visible age-related changes . These are animals with a developed form of social structure. They have an interesting reaction to stress: if it is very strong, then the diggers choose one of them and kill to relax. After all, someone must answer for the disgrace. Much like the response to fear in human society.
Gero scientists are inspired by the examples of the naked mole rat and other ageless animals (with so-called negligible aging ). The absence of visible signs of aging in a significant (and constantly growing) number of species makes one think that aging is not a law of nature, nature has already made many animals ageless. Even more interesting is that the turning off of aging occurred in different animals in different ways, which gives hope to us, humans.
In humans, the risk of death doubles every 8 years, starting at about age 40. If our health could be kept at the level of 30-40 years, then life expectancy would be 300-500 years. If you are now 30 years old, then you will most likely live another 40. If you are 70 years old, then you will live, probably another 10, if you are 80 years old, then you have a few years ahead of you. That is, life expectancy is constantly decreasing. And a mole rat at any age, according to the state of his body, has 30 years of life ahead. He does not age, that is, his body does not experience any functional deterioration in its condition.
Blood of the young and the dead
If you connect the circulatory system of a young and an old mouse, then the old one gets younger, and the young one gets old. That is, there is something in the blood of old animals - molecules or cells - that prohibits stem cells from participating in the regeneration of damage. For example, if you send young mice to the treadmill with stem cells from old mice, then the next day they will build muscles from these same stem cells. Older mice cannot gain muscle mass not because their stem cells are somehow damaged or not functional. Experiments show that surrounded by stem cells (most likely in the blood) there are aging factors - molecular signals that suppress the "desire" rather than the ability of stem cells to regenerate.
England is a thrifty country. There is also a bank of frozen blood of already deceased donors who donated blood several times over the course of 15 years. Scientists from Gero examined the content of more than 1000 proteins in each blood sample and, using machine learning, identified the proteins that were found to be the cause of donor aging. Scientists with the help of antibodies blocked these proteins in mice, and for the first time in the world, after one injection, they obtained the effect of systemic rejuvenation. As a result of experiments with very old animals, it was possible to achieve a delay in mortality, as well as an improvement in the condition of the animal, determined by the functional, molecular and cellular signs of aging. Experts hope that drugs developed against the proposed target could become a potent anti-aging agent in humans.
Data analysis
A huge role in the search for means of slowing aging is played by the accumulated statistical data sets on the health and lifestyle of the population - the so-called biobanks. For example, within the framework of one of the English projects, for almost 15 years now, information has been collected on the health indicators of 500 thousand citizens, the results of blood tests, diet, education, all kinds of diagnoses, dates of death of parents, genetic research exome sequencing) and much more. During the observation period, a significant number of participants died from various diseases. With such a set, researchers can find out what factors, including genetic factors, determine the likelihood of disease occurrence and the survival of the sick. This provides a starting point for the development of new drugs.
Estimation of biological age, i.e. the risk of mortality from all causes can be assessed even by the spontaneous movement activity of the user of a smartphone or other wearable device. In 2021, Gero made a free mobile application GeroSense that anyone can download and use, and also released an API.for the wellness industry, health food, insurance and any other player interested in monitoring the user's health changes in response to lifestyle changes or medical interventions. With the emergence of such technologies, the healthy lifestyle industry must transform and offer people products with proven effectiveness, including means of personalizing recommendations for improving their health and the products and services sold to them.
Nowadays, in order to sell something in wellness, the law does not require clinical trials confirming a positive effect on consumer health, and clinical trials themselves are expensive and in many cases economically unjustified due to the inability to patent the products sold. Many of the previously fashionable options, such as multivitamins, turned out to be not for everyone and not as useful as we would like to present them to manufacturers. Also, all people are different. Something that will help one will harm the other and will be a useless purchase and a waste of time and energy for the third. As a result, the consumer is forced to rely not on objective data, but on advertising, fashion and luck when choosing just for him. The chances of guessing are not great. GeroSense aims to change this situation,enabling all stakeholders to receive health feedback non-invasively and completely transform the market.
Any stress increases biological age. When removing the stress, if a person is healthy, a marker of biological age 2-3 months back to normal, and she returns to normal speed after stressful experiences - to put it in a scientific way "reziliens" - is an extremely important indicator of health status, and a biomarker of human aging
In order in order to comprehend what resilience is, in our latitudes it is useful to recall a hangover - a characteristic feature, i.e. one of the markers of aging. At a young age, it is almost unimportant what and in what order to drink. But by the age of 50, people switch to high-quality alcohol for a reason - health no longer allows drinking cheap.
Questions of determining biological age are far from idle academic interest. During a global pandemic, the risks of death as a result of complications increase for everyone, but most of all it concerns the elderly. Suffice it to say that the risk of death from COVID also doubles every 8 years , i.e. as fast as mortality due to aging.
The goal of anti-aging biotechnology is to control biological age in order to prevent it from growing, or better yet, to reduce it. To feel 30 at 50. By the way, the difference in life expectancy between people of different social classes in developed countries is about 15 years.
Age and healthy lifestyle
What age is the border after which no sport and healthy nutrition will help? Relatively speaking, up to 25 years a person leads a healthy lifestyle in order to look better, and after 35 - so as not to get a chronic illness. Many will be outraged by my words, but as long as you do not have a chronic illness, then if you quit smoking, your markers - functional, molecular, cellular - will return to normal in a few months. Insurance companies are well aware of this. The same applies to sports: while you are doing it, the markers will change a little, as soon as you throw it - they will soon return to their previous values. After 35, look for either a good doctor or a good gym. Sports can delay the onset of chronic diseases. Going to the gym 10 times to extend life by 5 years will not work. You need to do sports constantly,otherwise the effect will disappear.
In developed countries, oncology is now taking the first place in mortality instead of heart disease, as it was before. By the way, Moscow is very similar in the structure of chronic diseases and mortality to developed countries. The age of the first disabling disease, from which the quality of life changes traumatically, has passed over 65 years. And if tomorrow there is a pill that will cure all types of cancer in one day, then at first mortality will decrease, but life expectancy will increase by only 2-3 years. Because those who are dying of cancer now will die in a few years from another chronic disease. By the way, if there is a chance when cancer appears, the survival rate has exceeded 50%, then there is no cure for dementia at all. All experimental drugs have failed in clinical trials. So if we don't stop aging,then by curing cardiovascular diseases and oncology, we will get an epidemic of dementia around 70 years old, which will lead to monstrous costs of treatment and care.
If you are 70 years old and you happen to be healthy, then participating in any clinical study of any anti-aging drug is the right strategy. Information on clinical trials is available. If you are 20 years old, then there is a fairly high probability that an effective anti-aging cure will be developed within the next 20 years. An interesting dilemma arises for those people who are now about 50 years old. Those interventions that are currently at the stage of clinical trials will probably be available in 5 years, but first they will be applied to very sick people. It will take another 5 years for doctors to get used to the new drugs, understand how to use them, and begin prescribing to those who are 50 today and who are conventionally healthy. And if you lose your health within the next 10 years, then you will no longer have time to take advantage of the results of the revolution in longevity. Those,who are now 40, who have 15 years before the onset of their first chronic illness, can be relatively relaxed.
Let me give you an example. Former US President Jimmy Carter recently developed skin cancer at the age of 90 and metastases in the brain. 10-20 years ago it would have been a verdict. Carter received experimental therapy and was completely cured. And he was also lucky that he got cancer at 90, and not at 70-80, like others. During this time, technologies were developed that made it possible to heal Carter, who, perhaps, will live for another 10 years.
Never before has the effect of a healthy lifestyle been so strong. It is small in itself, 5-10 years of life, but given how rapidly technology is developing, the growth can grow exponentially due to the emergence of new medical technologies.... 5 years on avocado and celery, and a gym instead of fries and a bar - and there is a chance that you will stay healthy until the breakthrough technologies of longevity appear. This year, the results of the experiment were published: as a result of a year and a half intervention - the use of a combination of experimental drugs - it was possible to reduce the biological age of the subjects by 1.5 years .
Overpopulation and society
In longevity, two types of solutions are possible: anti-aging and anti-aging. Rejuvenation, as mentioned above, has already been confirmed experimentally. According to Gero experts, it would be advisable to use the maximum tolerated dose of the drug, but for a short time, and the side effects will disappear within a month.
In the 1970s, it was predicted that by 2025 there would be many more people than it actually turned out. Population growth has slowed down. Instead of explosive, exponential growth, the human population is approaching a stable level. Today it is estimated that this level will be about 12 billion people.
Peter advises to pay attention to the works of our great compatriot Sergei Kapitsa (son of the Nobel laureate Pyotr Kapitsa, popularizer of science, creator of the program "Obvious-Incredible"). The theoretical story of Professor Kapitsa is dear to us not only because it is incredibly techno-positive. First (and most importantly), the theory predicted and explained the demographic transition and stabilization of the world's population 50 years ago, when signs of demographic change were minimal, and most futurists feared overpopulation and disasters.
Secondly, according to Kapitsa's theory, the maximum possible number of people living on the planet is determined not by the amount of available food or the influence of the human mass on the climate. It is limited by the rate of maturation and the transfer of knowledge to the next generation of people, that is, completely biologically, socially and even genetically predetermined (and therefore modifiable!) Properties, first of all, by life expectancy. In Kapitza's theory, world problems at the point of demographic transition, which we are all going through now, find their solution in the field of biotechnology and medicine.
Thus, the real challenge is not overpopulation, but a catastrophic change in the age structure. The proportion of the elderly will grow. This phenomenon is called the "Silver Tsunami" and promises a drop in productivity in an increasing number of people as a result of the development of chronic diseases. It is easy to imagine a scenario when elderly people will not be able to financially support themselves in old age: not everyone has savings that will allow them to live indefinitely.
Therefore, the task of biotechnology is to fix people at a certain age so that they can continue to work effectively. It's not about immortality, people will still die, but at least they will be able to provide for themselves longer. It is likely that insurance companies will pay for rejuvenation procedures, which will be more profitable to support their clients in this way than to pay for expensive treatment for cancer, diabetes and other age-related diseases. Rejuvenation will affect not only the ability to work, but also the childbirth.
With neuroplasticity declining after age 40, the idea of lifelong learning is fiction, ageism, and discrimination. But if there are interventions that will fix neuroplasticity, then the idea of constant retraining - to be involved in new production processes - will become real.
Perhaps longevity technologies will be used not only to make our lives comfortable longer, but also so that people can survive in some extreme conditions like the exploration of the Moon, Mars or asteroids. No one promises that life in the future will become easier. Perhaps we will live as long as we do now, but work 10 times more.
How to get into the industry?
All governments have a stake in tackling chronic disease and aging. For example, in Singapore, with a population of about 6 million people, the director of a clinical center guiltily said to me: “ You see, we have only digitized 2 million people so far, excuse me, but by the end of the year all". In addition, products at the intersection of biotech, IT and medicine will create tremendous added value, which only increases the attractiveness of this industry both for investors and for those who are thinking about changing their line of business. I am confident that six to seven-figure salaries, options and shares of future biotech companies are available to specialists in mathematics, data processing and analysis, and machine learning. All participants in this market need such people. If you don't have a similar education, then as a first step, you can go to the online school GeekBrains, which recently launched a course on big data in medicine .
Forecast for the future
According to Peter, within 20 years, with a probability of more than 80%, it will be possible to achieve Longevity escape velocity - a situation where biotechnology can add more years of life to people on average than people will lose in the same time. Where it leads? The answer to this question is beyond the scope of engineering discussion. Taking into account the achievements of IT, we may find ourselves in a digital concentration camp in which we will live not for 50 years, but for 500 years. But I would like to hope that we will live not only for a long time, but also fun.