Building Support for the War with Death
Mikhail Batin of Open Longevity answers questions about the future of aging research

It's a simple question. One that has a simple answer or, rather, a myriad of simple answers. Healthy lifestyle habits. Digital healthy lifestyle habits. Technology to monitor multiple health markers. In a nutshell, we have to sleep well, exercise for an hour a day and live as far from Antarctica as possible. Having said that, this simple advice comes with a lot of nuances and refinements.

There are hundreds of anti-aging clinics around the world. I think the only good thing about them is that they distract people from eating by keeping them busy with essentially useless procedures. The real gold comes from physical exercise, reduced calories, and a calm daily regime.

On paper I've just answered your question, but in all honesty I haven't.

My answer was very superficial. Just as easily, I could have advised you to become extraordinarily rich and purchase the fountain of youth. Or, rather, you could try and build this fountain by employing thousands of scientists to work tirelessly at your behest.

Furthermore, by focusing merely on a healthy lifestyle, we lose sight of other dimensions of the issue. We get derailed in comparing different healthy lifestyle methods and lose sight of the bigger picture—a truly large-scale solution. That is what I would like to focus on here. There's a legion of health specialists out there who can elaborate on the topic of healthy lifestyles without my two cents.

Preventative medicine suffers from any lack of consolidated peer review or general guidelines for clinical trials. Frankly, the word "nutritionist" makes me sick to my stomach. I have yet to see any quality peer-reviewed papers on the subject of nutrition.

If we were to discuss nutrition, I would suggest organizing and participating in large-scale clinical trials of any given healthy lifestyle fad. This would enable us to collect large amounts of useful data about aging. The details of this trial would be scope for a separate interview in itself.

Our general anxiety about our health leads us to look for immediate and practical solutions. This is a trap that breeds ample customers for the market of useless supplements, hydrolyzed placental protein and other so-called "wellness" clinics.

I would like to highlight the fact that at present we are discussing the wellness of a generally healthy person, whose health deteriorates with age.

Let us finally leave the subject of "wellness". The next point in our discussion is the fact that our lifespan depends on the quality of medicine and the speed of technological progress in general.

Unless there is a nuclear holocaust, we are all destined to get some sort of age-related illness. So, let me reframe the question somewhat: is there anything we can do today to outsmart the impending deadly illness by the time it arrives. Is there a way to prevent it from becoming lethal? Perhaps there will be a vaccine or certain prophylactic measures put in place. It would be great if preventative healthcare could learn to reverse the process of aging.

When we think about tackling aging, we find ourselves between the world of uncertainty and the world of endless tools and possibilities. The next step is to choose which of these tools we can use.

However, before we begin trying to change the world for the better, before we create a world without illness or suffering, we must first answer one question: who is this "we" exactly? We all have different capabilities and skills. Who exactly will tackle the issue of longevity? If we don't decide on the "we", this issue will remain in the realm of ideas and good intentions.

We could make a large list of necessary clinical trials, forgetting to answer one simple question: who will sponsor them?

Alternatively, we could say that the government should allocate a budget for the study of longevity. Having said that, we should be aware that the government already has its hands full with other important tasks.

Progress comes from money. It is not at all clear where we can find a superhuman who will not only raise awareness about the issue of aging but also get hundreds of billions of investment into, let's say, regenerative medicine.

What about something simple like longevity-related promotional and educational content for Youtube? Who will create such content? Who has enough skills and funds for its production and promotion?

It comes down to this: when we ask ourselves who exactly is it that can make a change regarding the issue of longevity? No single human can overcome death alone. No amount of talent or initiative is enough to overcome social inertia. No one man.

United, however, the most regular people can achieve anything they want. This is not a novel idea. I credit Nikolay Fedorov way back in the 1900s for developing this concept in his work "Philosophy of the common cause".

Every generation faces the same challenge: will they be able to unite against death? So far year in and year out people have failed at this task.

The so-called "blue zones", areas where people live longer, are a credit to these very people themselves. They have organised a lifestyle that is conducive to longevity. Loma Linda in the US is a particularly interesting case. It has a very heterogeneous population: diverse in character, not in genetic make up. Their lifespan is 10 years above the US national average. This is an example of "accidental" cooperation in favor of longevity. It is our job to turn this "accident" into a large-scale, purposeful endeavor.

Part of the answer to longevity is to surround yourself with other people who are interested in your existence. To develop and test large-scale instruments of cooperation in favor of radical life extension.

Let me suggest some of these potential tools. Or rather some of the necessary tools:

These are overlapping fields. In truth, there are many ways to achieve longevity. However, it is a costly quest, one that holds no guarantees. On the other hand, a timely death is 100% guaranteed if we continue to do nothing.

Chew on this for a moment, barring Qin Shi Huang—the founder and first emperor of unified China—no one, nowhere, not a single country in the world has made life extension a government priority.

As far as governments are concerned, people are all equal and, in general, mutually replaceable. In fact, governments are founded on this disregard of individual human life.

It is enough to ignore what governments proclaim and to look at actual budget allocation. It becomes self-evident that saving lives is not of utmost priority.

"How to live longer?"—in brief, we must build a new society.

Any scientist worth his salt working in the field of aging will be the first to tell you that radical life extension is possible. They make no hard and fast promises, but they definitely see potential in this endeavor.

We have inspiring proof in the form of life extensions of laboratory animals. Furthermore, there is no physical law that we must overcome to achieve the same result in humans.

What can I say; evolution is excellent at creating "life extension". Life expectancy within a species can differ 20 times, and between species—in the millions.

Man is learning to do many things better than evolution itself. Just look at the creation of the wheel, not to mention space exploration.

I began to notice hundreds of biotech startups, mostly in California, primarily targeting mechanisms closely related to aging. I don't believe any of them will be successful in creating the "elixir of immortality". However, their mere existence is a good sign. They can act as initiators of large-scale governmental programs, although I would be delighted if free enterprises were able to tackle this exceedingly difficult task.

To state the obvious, the best argument in favor of potential radical life extension would be the very act of radical life extension itself. However, at the moment, we are just at the initial stages of data collection, creation and testing of theories. The scale of these current endeavours is dwarfed by the enormity of the task.

We are nowhere close to having done everything possible to extend the lives of the maximum number of people for the longest period possible. This fact is irrefutable. Many scientists failed to conduct experiments due to lack of funds. Others left science altogether. The number of Master's and Ph.D. programs in the biology of aging is insignificant.

On the other hand, it would be dangerous to underestimate the enormity of the task itself. There is no simple solution to aging and there cannot be one. It could very well be possible that the solution to aging is comparable in its complexity to terraforming on Mars.

It could even end up to be an insurmountable task. But wouldn't it be nice to know this for sure? Our folly is that we are not even trying to find out if we stand a chance at all.

Here we face the Great Wall of Death as a derivative of human culture itself. Throughout our history, humans have been aware of our mortality and have tried to come to terms with it. In a way, the fight against aging is absolutely counter culture. It suggests putting all our plans aside and solely focusing on fighting death. This is very similar to what Nietzsche said about the creation of the superman.

The idea of immortality goes against all our traditions, rituals, and stereotypical behaviors. I can name a hundred reasons why we are moving so slowly. Let me elaborate on one: people don't believe they can live long enough to witness the technologies of radical life extension. They don't believe that any of this can depend on them.

It is just easier to not dwell on dying. It is easier to take the familiar beaten path of death.

The fight for life is not a question of faith. It is a game of low odds but with incredibly high gains. Mathematical expectation will be on your side if you value your life high enough. Don't you find it strange that I find myself having to talk people into paying attention to life extension?

In regards to our biological makeup, the hard part is that we are made much like a disposable, useless thing, whose single evolutionary task is to spread its genetic material and disappear.

This likens our personality to a kind of parasite that resists the power of its own genome. So far, we are not even sure what exactly this personality, that we are trying to save from death, really is. We are as yet not aware of how our inner experiences work.

Yet another necessary task is the modeling of our brain functions.

We are always trying to understand what is the most important thing we can do to increase research.

First and foremost, we are a conscription service: we recruit people to fight death. We create and distribute a lot of content egging people on towards action. This creates a lot of mutual or independent projects. It's a growing field.

In a sense, we are old fashioned and believe in the power of books to change the world. I hope to soon see the publication of our work "Aging: it's complicated".

In the realms of science, we are interested in targets that can be manipulated to retard aging. Our next priority is the creation of an open database focused on aging.

By the way, the fight for longevity has its own trends. Last season was cellular senescence. Today it is transposons, which we are also interested in.

However, first and foremost, we are looking for future project leaders. Not so much in the fields of research as in projects aimed at changing public opinion and mentality.

A lot, actually.

There are quite large-scale efforts to create a method to diagnose aging. After all, we need to understand this process in a numerical format. We must have a reliable system for measuring age-related changes. The priority here today lies in various epigenetic clocks (a set of epigenetic DNA tags that can determine the biological age of a tissue, cell, or organ).

These diagnostics-related ideas breed a host of various advisory services. Instagram is littered with advice on rejuvenation. Occasional accounts even reference scientific articles. None of it looks particularly salubrious. There are no large-scale human clinical trials that can confirm or disprove the veracity of this advice. There are no consolidated opinions from the medical profession, nor are there any clinical recommendations. It's necessary for us to first and foremost agree on standards for diagnostic tools and preventative medicine.

The number of applications for mobile devices and various health-related gadgets is growing exponentially. Obviously, collecting and processing an avalanche of new data will bring tangible benefits. You don't have to be a big futurist to assume that disease prevention gamification is the next big step.

The emergence of longevity tech is another important trend. A hundred biotech startups with capital ranging from $10M to $3B have addressed hot topics in aging and are conducting clinical research.

Gene therapy and molecular design are gaining ground. The idea behind molecular design is to come up with unusual molecules with desired properties. For example, we need to come up with new ways to get rid of the crosslinks in collagen.

Also, I really hope that aging will soon attract people and technologies from the field of cancer research.

HARPA (Health Advanced Research Projects Agency) is a wonderful new initiative of this year, and it would be great to have this in healthcare. Perhaps the US Congress will give them $6.5B.

By the way, I can recommend the book "Immortality, Inc". There's quite a fascinating description of how the smartest and richest people came to grips with death. Surprisingly, the leaders of Google and Amazon are in on it.

Longevity lacks good big data. Therefore, I like the INSPIRE project, which aims to collect functional and omics data on aging and create a biobank in France.

Singapore has announced a life extension program, but little has been heard of it since.

As usual, there are some technologies which carry hopes for a slight increase in life expectancy. For example, transfusion of young blood plasma with albumin solution. However, putting one's hopes on simple solutions is not worthwhile.

Today, it's blockers of retrotransposons and inhibitors of reverse transcriptase. I will name a couple more areas: blockers, antibodies to oxidized phospholipids; fatty acid synthase inhibitors; we have yet to hear the last word regarding the field of senolytics and senomorphics.

Senolytics are drugs designed to kill senescent cells that interfere with the normal functioning of tissues. Senomorphics are drugs designed to act indirectly, blocking the actions of senescent cells.

Decaying cells were almost unknown to science 15 years ago. Today, not only are they being studied, approaches have already been proposed to block this aging mechanism. Let me say a few words about the three most unexpected solutions that have emerged over the past three years.

In the first case, American oncologist Scott Lowe and his colleagues used specially modified immune T cells to remove senescent cells, which express the so-called chimeric antigen receptor (CAR). As a result, they got the very same CAR-T cells that are now much talked about in professional circles.

Previously, they were actively used in immuno-oncology to remove degenerated cells. Now we are seeing a real boom in clinical research on CAR-T cells. According to ClinicalTrials.gov, several hundred clinical trials of related therapies are underway. Since the end of the 90s, there have been 5 generations of CAR-T cells designed.

Now, CAR-T cells have been successfully tested by oncologists as senolytics.

In the second case, scientists have shown the ability of extracellular vesicles to fight senescence. Vesicles are bubbles surrounded by a membrane. They are secreted by cells, in large numbers by stem cells.

Today, these vesicles are very actively studied as therapeutic agents for the transfer of healthy biological cargo, proteins, nucleic acids, and low-molecular-weight drugs. Their recently described role in senescence is interesting.

Back in 2019, English and Spanish scientists described how decrepit cells secrete vesicles with the IFITM3 protein, which literally infect normal cells with senescence, causing them to age.

There was a recently published study about the reverse process: vesicles from young cells reduced cellular aging in an old body, reducing lipid peroxidation. The key molecule carried by the "young" vesicles was the antioxidant enzyme GSTM2, a large amount of which is characteristic of long-lived species, for example, naked mole rats.

Before that, in 2019, there was the work of American biologists from Johns Hopkins University. They found an important antioxidant enzyme, peroxiredoxin, in extracellular vesicles from induced pluripotent stem cells (iPSCs). Most importantly, iPSCs are champions in the number of extracellular vesicles. They secreted them almost 20 times more than the other type of stem cells, the mesenchymal.

In my view, vesicle therapy is likely to become a fundamental new type of therapy.

The third approach to combat senescence was described quite recently, in May of this year. The Americans from the University of California were able to activate special immune cells that fight aging—invariant natural killer T cells (NK cells).

Tested in two animal models, obese mice with fibrosis, the activation used alpha-galactosylceramide (a-GalCer), a well-known lipid antigen that specifically activates these immune cells.

As a result, senescent (decrepit) precursors of fat cells were removed in obese mice. This is a potential approach to fighting obesity in old age and to prevent the development of diabetes.

And in the fibrous model, cleansing from senescent epithelial and mesenchymal cells led to a slowdown in profibrotic processes. This will allow virtually all older tissues to perform better.

I have just considered a small but important topic in aging—the fact that cells become decrepit and damage tissues and that cells can be cleaned.

There is potential for new therapies here, but there is no single institute for the exclusive study of senescence, there is no single-state program—the study of aging is as yet terra incognita. Even Nature thinks so, publishing in May another article, "An aged immune system drives senescence and aging of solid organs".

We will talk about scientific problems in more detail in our new book. Hopefully, it will come out this year.

We can say that this has been a hot topic for over a century, but, so far, there is no consensus on any issue. Even on the existence of aging itself, there is no consensus; maybe it is best to avoid using a term that could not even be defined?

When they say that aging is an increase of the likelihood of death, and they do not describe what happens physically, this reveals a lack of understanding of the very process.

It so happens that theories of aging follow the major discoveries in biology. They discovered immunity—there will be an immune theory of aging, hormones—the hormonal theory of aging, epigenetics—the epigenetic theory of aging.

Now, there are many works in the field of alternative splicing—we can totally put forward an isoform theory of aging in response.

At the same time, there are a lot of ethics involved in our understanding of aging: aging is something bad. It is a violation of physiological functions, a breakdown. Thus, aging begins to cover everything we know about the body. As a result, we begin to get bogged down in all this comprehensiveness.

Maybe, in order not to drown, we need to focus our attention on something: here is a chronic non-infectious inflammation, let's study it and do something with it; here is mitochondrial dysfunction, this subject is also clear; let's lower the level of non-enzymatic glycation and see what happens.

I emphasize that we do not yet know which strategy will be the most effective. There are roughly twenty branches of aging studies, and our knowledge is increasing.

The science of aging has achieved the following: we have learned a lot and are more confused. Since the dominance of the oxidative theory of aging, there has been less clarity. We can say that our ignorance is growing exponentially.

Basically, you need to take the most important interventions of the past twenty years, from rapamycin to IGF-1 inhibitors, and ask yourself why they didn't work? We need to focus on the inefficiencies and side effects of potential geroprotectors. What is it that is always in our way?

So far we have found out that a mouse is not a human and that 30% of life extension in mice does not carry over to humans. We need to understand why that is so.

At the same time, of course, we should avoid negative spell casting: "everything is so complicated, tangled and difficult". Yes, it is difficult, but we must rush head on into this complexity. All knowledge about aging should be well structured.

You can add stem cells. The first bone marrow transplant was performed 62 years ago by Georges Mathé, a French oncologist, but these are alien cells, of course, and if you just inject donor stem cells, rejuvenation does not occur. What does occur is profiteering off gullible patients. I wonder why there are still no high-profile criminal trials in Los Angeles regarding all of these procedures.

As for organ growing, I think we need to focus on therapeutic cloning. That is, growing clones of our own organs. After all, we can roll back a cell to a pluripotent state, and if so, theoretically there exists a combination of influences, including various growth factors, enabling the desired organ to grow from this cell. Of course, a new generation of bio incubators will be required. Regenerative medicine needs to move in this direction.

Yes, stem cells are shrinking, and this is true aging. If we could effectively increase their quantity (without losing quality), this would be a solution to one of the problems of aging, blocking one of the harmful mechanisms. The problem is that the existing products on the market do something completely different: foreign stem cells almost never take root, even the host's own cells rarely take root, since this process requires complex factors and conditions.

If such therapies do have an effect, then it is achieved due to the molecules secreted by these cells in those hours and days before they have died.

In particular, we are talking about the development of exosomal therapy. The cell can release into the surrounding space both free molecules and exosomes packed in special bubbles, also called vesicles (I have already spoken about them). Modern science is very interested in this delivery method. And by clinical research, I mean Longeron, not what is happening in the Bahamas, of course.

Perhaps there is a possibility of a non-trivial alternative approach. Aging is an extremely complex thing, and it is not yet clear how we can create a cocktail of drugs that prolong life. The idea is to try it out blindly. We need to organize and train a certain biological system that can have a suppressing effect on the aging of the body. Yes, the topic is quite speculative, but I think we need to go in this direction as well. Michael Levin suggests something similar.

Let's ask ourselves a question: what must happen before a cure for old age is found? Since the task is large-scale, probably some huge project should be created. When can this happen?

Let's consider the arrival of billionaires in this field as a marker of progress. Their number is growing, but they are focused on commercial projects, which seems to me to be a mistake. At some point, I think the concept of radical openness will prevail in aging research. To be precise, I am sure of it. It is necessary to build such a schedule and see at what point in time there will be 100 major players.

It will probably take another 10 years to create a megaproject. Then 10 more years for us to extract the first results on human life extension from the colossal amount of data. It will be sometime 2040–2045. The very same dates coincide with the forecasts on the possible emergence of a strong AI.

I would turn the conversation from predictions of when we learn to extend a person's life to talking about a plan to make it happen.

Who has the best plan in the world, and how long does it take to get it done? Calico? It seems unlikely, no. Facebook with its cell atlas? So far, no results have been heard of.

The clearest position has been and remains with Aubrey de Grey. Regardless of how we may feel about him, on the topic of aging, he is the most intelligible dude in the world. Until this year, he had a budget of $5M a year. When will he have 5 billion? This does not mean that it is he who will create the technology, but the budget of his SENS foundation is a marker of society's attitude towards the fight against aging.

Creating a cure for old age is about implementing a clear plan, a clear strategy. Create a strategy, and you have a deadline.

This is a very important thought: we need to be clear about the chain of events that must occur before the creation of technologies for radical life extension. It is on them that we must focus our attention. Let's say we believe that a cure for old age cannot be created without a major international project.

This means that in, let's say, the EU itself, some political processes must take place that will lead to the expansion of the Horizon program. What could drive such an initiative? First and foremost, civic engagement.

A large part of the fight against aging is in the collection of databases. If we are talking about the control of genes over lifespan, then we must have all these "lifespan" genes collected. We carry out a small part of this work, although it is subject to criticism. They say it is impossible to formalize all knowledge about genes associated with aging. Our position is quite simple: let's look at the whole picture, to the extent that it is available to us now. And then we will see how useful it is, for example, in selecting a combination of potential geroprotectors.

All DAMP, SASP, changes in immunity, lipid, various omics data, cell atlas, and the actions of potential geroprotectors and their side effects must also be transferred to the databases. Transcriptomes of different tissues of people, of different ages.

Datasets are needed to develop diagnostics of aging to understand the early pathogenesis of age-related diseases. We need open data on human aging.

As I said, the fight against aging is about getting good new data and careful processing of the data that has already been obtained. In particular, we need data on changes in the transcriptomes of every human organ, in different ages. Such work has not yet been carried out anywhere in the world. It costs several hundred million dollars. But without it, we would not know how a person grows old. It must be an open dataset. Who will pay for this? Who will pay for open-source aging projects? For all the primary data to be published and not to be under any patent protection.

I think, without open-source projects, we will not be able to revolutionize aging.

Of course they do. Research is ongoing on all fronts. If the technologies that are now being created in the fight against tumors can be used in the partial removal of senescent cells, and these, in turn, still turn out to be a serious cause of aging, then this will be a breakthrough. The same goes for epigenetic retracement. Pharma is working, and we are closely monitoring everything that happens, but we want more. What approach can overtake all biotech? Open data. Then there will be no hiding of data due to commercial interests, and we will have an increase in the speed of development and the level of expertise on what needs to be done in the first place.

We will proceed thusly: We initiate an open non-profit project in aging that we will declare as being the best. This will be true because it will be one of a kind. Then, we will propose others to create a project that would be better. Perhaps we will announce a prize. Thus, we want to launch an avalanche of non-commercial projects.

The point is that life extension is valuable in itself. It's nice to make money, of course, but it's better to stay alive. Therefore, we need to remove this weight of compulsory commercialization. Korolyov would not have launched Gagarin into space if he was required to pay off the flight around Earth.

Our task is to convince philanthropists that this approach is correct. The amount of money in a non-profit approach is generated from the number of volunteers who are willing to spend their personal time on the goals and objectives of the NGO. We have a big-enough problem here. Research on aging itself requires a lot of knowledge. This is not a volunteer garbage collection, when everyone can go clean up the park. We want volunteers to perform non-trivial tasks. What solutions can there be?

Raising awareness of how aging works. Timofey Glinin gave 12 lectures on the biology of aging and posted them on YouTube. There should be a thousand lectures of such that would most fully cover the field of aging research. There should be a unified course following the example of the Khan Academy.

Another approach could be patient-driven clinical trials. Of course, it is not the patients themselves who should conduct the research, but initiate it, and the research would take place in an organized manner. Perhaps what is now called biohacking may turn into patient research.

Nevertheless there is still no strong solution out there for those who would like to invest their time into radical life extension. We have to keep on experimenting.

There are many alternatives. For example, cyborgization of organs, artificial blood. We would get rid of half of the problems if we learned to artificially deliver oxygen and nutrients to the brain.

I think a head transplant, or rather a body transplant, is a good alternative. There is a rather important stage here: the maintenance of the vital activity of the head of a large mammal outside the body. It would be great to set a world record in this area. A simpler step is the exchange of circulatory systems between animals, so that the heart of one pumps blood for another. I wonder what would happen if these animals were clones.

Let's think about this. If we make the value of human life absolute, then inaction, missed opportunities to prolong life, becomes the true evil.

Religious figures often hide behind talk about bioethics in order to slow down progress. Just look at the ban on human cloning. Naturally, we should not clone a person if we are not sure that the clone will be healthy. But to prohibit cloning because of the assumption that a clone will not possess a soul is going too far.

Experiments on animals are a necessary evil, otherwise we would not have medicines and medical technologies.

Talking about heritage. If today, we were to set up a major international conference on aging in Europe, attended by participants from many countries, do you know what the most frequently asked side question would be? Why are there so many Russians? 30% of the participants would be Russian speakers.

This is that kind of continuity. The Russians are very much in favor of the idea of ??physical immortality. We do not notice this in Russia, but actually we are very strong in transhumanism. I think that in the next few years, organizations with Russian roots will reveal themselves.

I don't know about the result per se, but I began to like Sergey Young's activity more. It is picking up momentum.

I would like to believe in Gero's company, but I take it partially on faith, as I do not understand their complex physics.

Michael Greve from Germany announced today that he will invest $362M in rejuvenation startups. He comes across as the most competent investor in Europe.

Many scientists are doing interesting research.

I've just read Rochelle Buffenstein's article on epitranscriptomics today. Another universe of aging research has been discovered.

Separately, I would mention the main fighters against protein crosslinking in the extracellular matrix, David Spiegel and Jonathan Clark. These stitches are one of the key barriers separating us from longevity. Extracellular matrix proteins are crosslinked by sugars and stop working normally. The matrix becomes rigid and triggers entire chain reactions of pathological processes associated with epigenetics, genomic instability, mitochondrial dysfunction, stem cell depletion, and more. Spiegel and Clark, with the support of Aubrey de Grey's company, are actively studying this cross-linking of matrix proteins.

Last year, they managed to create an antibody that specifically binds to glucosepane, one of the main matrix cross-links. This will enable us to measure the amount of glucosepane in tissue.

A year earlier, Spiegel and his team tested the bacterial enzyme MnmC in action. Their work has shown positive results in breaking down two key glycation end products (AGEs) that also contribute to aging: carboxyethyl lysine and carboxymethyl lysine.

At the same time, we know that bacteria and fungi have a considerable evolutionary arsenal to combat AGEs: glycopeptides, metalloproteases, amadoriasis, and deglycases.

Let this be my refrain, but here too we need an institute, an international research program, and not just five laboratories with small budgets.

It is customary in our region to scold Calico, but I think they should finally be able to get somewhere with $3B.

You know, I also like what is happening in the Russian segment of Facebook on this subject. It seems to me that the right processes have been set in motion there, and wonderful collective intelligence is being created. I am one of the chefs in this kitchen of immortality. Subscribe to my Facebook account.

First of all, I would recommend spending 10% of the proposed investment on open research and on a non-profit approach. Or better, 100%.

Longevity startups are now dominated by an aggressively naive approach. These people believe they've caught God by the beard, so money is poured on simple solutions: like now we will remove bad cells or add a "longevity gene". There is no lack of funding for this kind of approach. Any given Stanford professor promising to find a cure for old age sometime a little later, but for now needing to conduct clinical research on a different nosology, albeit closely related to the mechanism of aging, will easily find funding.

There is little money available for the establishment of cause-and-effect relationships in aging, for the evolutionary-comparative biology of aging, for open data on human aging.

You can make money off the hype, but is this what we want? We need true life extension.

Aging as a problem is huge. There is no need to worry that you will not have time to profit from selling the elixir of immortality. If you're late and someone else is making money on radical life extension, that's great. This means your life expectancy has increased. Now there is time for further enrichment.

Nevertheless, I admit that I could be mistaken, and it is businesses who will prove capable of creating at least a weak cure for old age. Perhaps the conditions for particular financing are as follows: either commerce or nothing.

Then we have to answer the question: what do we, as startups, know that Calico or Pfizer does not know? They have no problems with money, they have the best specialists, and they work all the time. What is our strength?

First of all, you need to invest in improving the competence of the analysts who work for you. A very strong American full-time professor costs $200–300K a year. There should be several such people working exclusively for you.

Second step. Use the stock exchange as a way to test your competence. If your team is focused on research related to inflammation, then you should probably pick up a good package on the NASDAQ by reading the results of clinical studies. In pretty much every direction, wherever you go, there are already listed companies working on similar tasks.

Third step. It sounds strange. Choose a totem animal. It is possible that evolution has already solved the problem that you are solving in prolonging life. Maybe learning how she did it for a particular organism will help you develop technology.

I also think that when investing, you need to keep a certain focus. Don't get scattered into dozens of different directions, but invest in companies from the same sector working on similar tasks. This will increase the investor's own competence. Yes, it is better to know one topic than spread yourself too thinly. On the other hand, avoid depending on one single company; work with several different ones.

I naturally do not provide investment advice. I can only speculate about interesting research areas in which technology can be created.

We already mentioned splicing when we talked about the theories of aging. I should mention the main researcher of changes in splicing during aging, an English biologist Lorna Harries.

The story of splicing and aging began recently, in 2016, when several publications came out describing age-related changes in splicing in different species, from worms to humans. Before that, they already knew about the changes in splicing in various diseases.

What is splicing, and why is it important? RNA splicing is when introns and exons derived from a gene's DNA sequence are removed and combined into the final RNA sequence from which the protein will then be synthesized.

Introns are usually discarded, exons remain. They can be shuffled in a clever way, making it possible to synthesize different proteins from a single gene. This is called alternative splicing.

All these processes are disrupted during aging, which, of course, negatively affects the functioning of the body, and, as studies show, it may be one of the causes of aging.

Despite the complexity and importance of this area in the fight against aging, only one team, led by Lorna Harries, is engaged in this research. The biotech startup SENISCA was created for this. I must say, they already have had some successes; they were able to identify the key molecular players in these aging processes.

Of course, in the naked mole rat, splicing processes are very stable throughout almost its entire life. How could we leave it out of this discussion?

Another team of scientists who are doing a lot in the fight against aging are the Spanish biologists Reinald Pamplona and his colleagues. They became known in the early 2000s as the first to show that limiting the amino acid methionine has a positive effect on health and longevity, and then they actively studied the processes of lipid peroxidation.

Lipid peroxidation is when the lipids of cell membranes attack free radicals. Then, chain reactions occur, when some oxidized molecules oxidize the next, and so on. The metabolites of these reactions can form the end products of glycation.

The most susceptible to lipid oxidation in membranes were polyunsaturated acids. Scientists have traced an interesting correlation. The less unsaturated docosahexaenoic omega-three fatty acid there is in the membranes, the longer the species lives.

So, in mice, this acid in the membranes was 9 times higher than in naked mole rats. Based on this data, Pamplona and colleagues have put forward their membrane theory of aging. This suggests that the composition of membrane fatty acids, through its effect on lipid peroxidation, is an important factor in life expectancy. It sets the pace of aging and links metabolism to longevity.

Fighting lipid oxidation is a very promising topic, and I think new blockbusters will be created here. In general, there are many areas of work.

You probably want me to name the tickers of all the promising companies? I need to think more about this. We are currently conducting an in-depth analysis of all the biotech companies associated with longevity.

Academia too has its problems. Its structure is wildly archaic. It is like some sort of feudal slavery system. Graduate students from all over the world, young postdocs are humiliated. They essentially act as "science slaves" to their master, the "serious scientist". Low wages, lack of freedom, and a strict hierarchy make 90% of people leave science.

We are left with a lucky 1% who happen to be good at marketing and self promotion and have an eye for legal subtlety.

Basically, by the age of 40, a scientist feels he's been deceived: there's few perspectives and a lot of lost hope. Academia's efficiency is extremely low. The rat race for survival results in lots of trashy work; a lot of experiments cannot be reproduced in part because of false data that was supplied for the sake of receiving further funding.

Novel organisational solutions are the super task. A very good example is how Elon Musk created Neuralink.

In spite of all this, I am not only a longevity optimist, I also believe that we must strive for an unlimited lifespan, for the physical immortality of mankind. I believe in the incredible power of the human mind and the unquenchable desire to live. At the end of the day, the work of tens of thousands of people will bear fruit.

We need to closely monitor potential drivers of social processes. For example, it might be transhuman art. Art that evokes the desire to act in favor of extending the human potential.

As for the odds. We will stand a good chance when we have a good strategy. Look, the fight against aging is extremely difficult at the molecular level. But it is no less difficult at a social level. We need to press thousands of levers, spin millions of wheels of public order, to be able to radically change the situation in favor of prolonging life.

Enumeration won't solve these tasks.

What is the current solution for raising funds? By increasing the amount of content related to scientific achievements. It is believed that people with resources will read a lot about aging and start spending private and public money. It is working, but not at all to the extent that we would like it to.

There are no strong longevity lobbyists in the world because no one pays for such work. Private funding goes to venture capital.

We need some sort of devious strategy. We must use the scientific method not only in the laboratory but also in the organization of social change. Here, we also need big data, but of a different nature: what role the struggle for life holds in public minds and what the factors that can influence public opinion are.

Now, these are the direct tasks of our organization, Open Longevity.