Aging Expert Dr. Alex Zhavoronkov Discusses Future of the Longevity Space

November 27th, 2020

LifeScite interviewed Dr. Alex Zhavoronkov to get his insights on the aging field, its most recent developments and upcoming ventures. Aging is a relatively new research field that focuses on identifying the multitude of factors that contribute to a persons decline and intervening in the hopes of extending longevity.

To learn more about aging and longevity, read our article about the field HERE. 

Transcript of the interview. 

LifeScite: Today we have Dr. Alex Zhavoronkov here to share his insights on the current state of longevity medicine and the next wave of aging research strategies. Dr. Zhavoronkov is the CEO of Insilico Medicine, which is a company that’s using artificial intelligence, for drug discovery and aging research. He is also one of the leading longevity experts cited in over 130 papers and has published two books. Thank you for joining us Dr. Zhavoronkov.

Dr. Zhavoronkov: Thank you for having me.

LifeScite: Can you give our listeners a quick overview of the longevity and aging field.

Dr. Zhavoronkov: It will be difficult to make a short intro into the longevity industry because it is broad and encompasses many fields that also relate to general biotechnology, pharmaceutical and healthcare.

I would define longevity medicine as a field of AI powered preventative medicine focused on biomarkers of aging. Recently, the longevity industry has advanced quite dramatically. Just in the last ten years, we have seen convergences that integrate soft sciences like information technology with biotechnology. This union resulted in the discovery and rapid adoption of a technology called aging clocks or biomarkers of aging.

Aging clocks were originally developed on methylation data, so epigenetic data by Steven Horvath and the Hannam group from 2011-2013. Our group picked up the trend and converged it with artificial intelligence and developed a range of deep biomarkers of aging or deep aging clocks.

We have a variety of aging clocks built on blood tests, transcriptomic data, proteomic data, methylation data and aging data. Pretty much any data that changes in time. This allows us to tangibly measure aging. I believe that this introduction will be the next-generation of the longevity industry.

LifeScite: How about the therapeutic side? What are some drug candidates targeting aging?

Dr. Zhavoronkov: I like to break therapeutics down into 5 areas.

1. Rapalogues, derivatives or analogues of rapamycin. This was an old drug used in transplantation, in cancer and in immunology. While it sounds scary because of the severity and toxicity of those diseases, rapamycin is rather mild and many rapalogues have substantial promise in aging and multiple age-related diseases.
2. These are drugs that target senescent (old) cells and allow for cells to be replenished, to be recycled. So, think of it as a universal recycling method that does not allow the old cells to stay and pollute the microenvironment. There are multiple approaches to this kind of challenge of recycling and there are multiple senolytic companies that are emerging. Recently, there was a paper in Nature Biotechnology on senolytics called, “Send in the Senolytics”.
3. NAD boosters. Multiple groups worldwide discovered that elevating the level of NAD+ molecule at the cellular level results in increases in health and lifespan in model organisms. Now there are experiments on the way in humans and molecules like nicotinaminde riboside or nicotinamine nucleotide are actively now consumed as supplements but also are used in clinical trials.
4. This is an old diabetic and pre-diabetic drug and now people of all ages are also taking it for longevity. There is a clinical trial on the way called TAME that targets aging.
5. Alpha-ketogluterate (or AKG). This includes work out of the Buck Institute and several other top research facilities. AKG is off patent and thus difficult to get IP protection, similar to many of those molecules like nicotinaminde riboside or nicotinamine nucleotide. It looks like it holds a lot of promise in aging and age-related diseases as well.

LifeScite: In addition to the five promising pharmaceutical areas you mention, there is also increasing interest in the field of regenerative medicine. How do you see this contributing to longevity?

The main drivers of regenerative medicine are stem cells, organ transplants and endogenous regeneration. Aside from the consumer application of stem cells, primarily in China, we do not see large companies getting into the stem cell therapeutics field. It is still at the early research stage, even thirty years after the first treatment with stem cells. I am hoping the next decade will yield dramatic advances in regenerative medicine and stem cell therapy.

There is also gene therapy that is at the early research level. We will not see dramatic clinical advances in gene therapy for aging for the foreseeable future. I would say maybe ten years.

LifeScite: You mention that some of the areas in aging are in the early research stages. What are your expectations for the aging field in the next decade?

We are starting to see companies and even clinical centres combining diagnostics and therapeutics. Unfortunately, we do not see this industry being perceived as credible by the insurance industry and by large pharmaceutic industries, yet at least. We’re getting there but we still have a long way to go.

I think that in general, the longevity industry is pretty early in its development, so we don’t see the hype in longevity yet. We do see the venture capital industry getting into the field, so early stage venture capital companies are getting in. There is an emergence of those companies. They are funding all kinds of projects, credible and uncredible and its great. This investment reminds me of the social networking era, or the era of computing where people were betting on all kinds of projects during the dotcom boom.

I think that we are going to see a major boom in aging within the next decade or two. So, if you are a young pharmaceutical executive or if you are a medical student, I would take this industry as a priority for career development. On this front, we just recently launched a course called Longevity Medicine. This is an introduction to longevity medicine for physicians. It’s available at www.longevity-medicine.org and you can take it via Udacity or LabXchange or other platforms.

We are going to be putting more and more courses for people to get into this industry, for both physicians, general public and even investors. You will be able to take it as a continuing program to improve your skills.

Large tech companies are getting into the field and are on the borderline of longevity and digital medicine so all those apps and trackers that track you in time, measure very useful data that we can use for longevity research. But I haven’t seen anyone openly coming out and saying, “we are going to use this to extend human life.” Except for our company, Deep Longevity, which is very actively involved in this biomarker development process and of course we are very vocal about the focus of the company.

LifeScite: Up until now, drug development has been on treating age-related diseases. How do you and your company, and other companies in the field go about preventing age specifically. Some may argue that you’re fighting Mother Nature.

Dr. Zhavoronkov: Nature is not your friend on a personal, or even species level. It wants you to come into this world, reproduce and then die. It wants you to compete for survival, not necessarily improve. So, we are not fighting Mother Mature, we are improving it because nature is imperfect. We need to find design flaws and try to fix them, or completely rewrite them. Unfortunately, it’s not easy, so we are trying to do it in a very credible way.

In our company, we are not trying to diagnose diseases. Rather, we are trying to develop biomarkers that tangibly track age. You can actually think of aging as a disease with hundreds of stages. With artificial intelligence and more advanced statistical tools, we can tangibly track the progression from one stage to the other and rank them by importance. We can see which most important features are causal in aging and try to intervene. Essentially, we can understand the symphony of aging and try to direct it.

That’s what we’re doing at Insilico. We are developing a variety of interventions that are comprised of something that’s already available, you like eating well, sleeping adequately and exercising. We can now work with those lifestyle behaviours and optimize them for longevity.

We can also start incorporating some of those advances that I mentioned, into more clinical regimens. However, it’s not easy to conduct a clinical study for aging. Unfortunately, you have to go after some disease to be able to make a business case. With some of the very advanced pharmaceutical companies, we are working on protocols for clinical trial enrollment using aging clocks.

LifeScite: Aging clocks are a relatively new concept that have been helping in longevity research and aging in general. Is the data being used to compile aging clocks accessible to the average person? If so, how can somebody access such information?

Dr. Zhavoronkov: It’s now very accessible to use due to an app launched by Deep Longevity, called Young.AI. You can log in a substantial amount of anonymous information about yourself and it will turn it into clocks. You can also upload a variety of data types for your age to be predicted and for the aging clocks to be interpreted.

LifeScite: This past August, a well-known longevity company called Unity saw that its lead drug candidate failed. How do you think this affected the longevity industry? And what do you think other companies learned from this hiccup?

Dr. Zhavoronkov: I think the experts in the field and the pharmaceutical companies, this failure did not really make a difference. If you are in big pharma, you know that more trials fails than succeed. In phase 2, you usually have a 70% failure rate.

Second, it’s the first trials of its kind, so the company needed to choose a disease indication that is relevant to their treatment. It’s not necessarily the best choice of disease because the intervention they chose is hard to track. I don’t think that the target they chose is right. I don’t think that the trial was perfect. However, I do think the company deserves a second, even a third chance.

On the surface, for uneducated investors and industry outsiders, it’s very negative. I think that the most negative was another failure by a company called ResTORbio where they used a PI3K inhibitor and their phase 3 trial failed. That probably affected the industry more than sinolytics.

LifeScite: Recently, your company, Insilico, signed two collaborations with pharma companies Taisho and Jansen of Johnson and Johnson. How do you view these collaborations and are they a sign that big pharma is expressing more interest in the field?

Dr. Zhavoronkov: Insilico itself is more of an AI company focused on drug discovery. It does tend to support companies and age-related diseases in areas that are associated with aging. We specifically spun out Deep Longevity out of Insilico to be focused on aging without investors and pharma companies. Some of them don’t want to partner with an aging company or don’t support the longevity industry because it is still a fresh and unproven field. So, the partnership with JnJ doesn’t have anything to do with aging.

Taisho Pharmaceutical has everything to do with aging because we are tasked to both discover novel targets for senescence and also produce novel molecules for senescence. Taisho is big business. It’s a moderately big company, top 100 in the world. Of course, this partnership is worth more than you can think of, in terms of potential for humanity. If it works, it’s going to be huge.

LifeScite: With this collaboration, specifically for your company, or the aging field in general, what do you expect to see in the next 3-5 years?

Dr. Zhavoronkov: For Insilico, I think that we are going to see some of our molecules going into clinical trials within the next 3 years. Specifically going into clinical trials for an age associated condition. We are looking for fibrosis and several others.

For Deep Longevity, we are already supporting the longevity industry in a big way. We launched the apps, the set of tools to track aging and we developed several artificial intelligence systems.  They help identify those features that make you look older or younger to the digital network and intervene. We are tangibly going after age reversal.

LifeScite: I learned that you function on about 3 to 4 hours of sleep a night. How do you supplement that lack of sleep? How is it that you stay sharp and healthy even with a fraction of the recommended sleep hours?

Dr. Zhavoronkov: That is definitely not very healthy, and I wouldn’t recommend it for anybody. But, I must say that I feel I am contributing to the field and every time I go to sleep, I feel that I am wasting time. Every second of the time that you are awake, somebody dies of aging.

In general, it’s also a huge economic problem so if we don’t figure out a way to significantly extend protective longevity, the economy is going to collapse and a lot of people are going to die.

So, what else is there to do? We need to accelerate and I’m just very dedicated to the field. I wish more people were doing that because you can convert time into money, but you cannot convert money into time.

We as human beings are very good at finding some kind of objective function to start maximizing towards a specific objective. In life, we optimize for money to give us some arbitrary measure but at the end of the day, there is nothing more important than time. Healthy time. We cannot really add that, at least not yet.

Would I trade places with Warren Buffet or some other people who have lots of money over more years to live? Even though they are incredibly wealthy, I don’t think so.

I think that the best strategy right now is to just work as much as possible to get this field off the ground. If you look at what’s happening in the field, there are not that many people who are trying to get it to the consumer and also to accelerate the research. In academia, people are trying to publish papers and are still working on diet and exercise so there is no sense of urgency there. In business, people are very skeptical its going to work.

Think of it as electric cars before Musk. If there are no Musks, you won’t have the industry. At the end of the day, you realize you have to work very hard to create this industry. There are a few of us there but there are not many.

LifeScite: Your dedication and your sacrifices are very much appreciated.

Dr. Zhavoronkov: I’m not sacrificing anything. I’m just optimizing. I’m actually very happy doing what I’m doing. I don’t think that there is anything better to do. I don’t need to sacrifice for something that I deeply love.

LifeScite: Thank you Dr. Zhavoronkov for all your insight and your knowledge. I really appreciate you taking the time to be here.

Dr. Zhavoronkov: Thank you and let’s promote longevity research in general. It’s great that you are doing it towards pharma. Those are the guys we need to play the big game.