The desire to live longer has created a strong and fast-growing longevity-focused industry trying to unlock the secrets of immortality. Alex Zhavoronkov is giving insights on his journey of tracking and hacking the mechanisms of aging using AI.
Alex Zhavoronkov has been interested in aging and longevity since he was a child. Today he is one of the key players in the emerging field of longevity biotechnology and medicine. He is founder of two global companies - Insilico Medicine, where he is a CEO and Deep Longevity, where he has an honorary title of a Chief Longevity Officer. Insilico Medicine is an AI company dedicated to extending human productive longevity by biomarker discovery and drug development for a number of diseases and aging, and immuno-oncology. Deep Longevity, now a part of publicly traded company, Ensurance Longevity (HK:0575), aims to develop explainable AI systems to track the rate of aging at the molecular, cellular, tissue, organ, system, physiological, and psychological levels. The company established a research partnership with one of the most prominent longevity organizations, Human Longevity, Inc. to provide a range of aging clocks to the network of advanced physicians and researchers. Alexander Zhavoronkov is also strongly engaged in networking, communication, and education. He has co-developed and launched the CME-accredited Longevity Medicine Course, which was developed to facilitate the adoption of the latest trends in aging research in the medical community, now taken by over 5,000 medical professionals, and launched on several national platforms for upskilling the physicians including HDR UK. Also, he is also co-organizing the Aging Research and Drug Discovery Meeting allowing renowned experts in the pharmaceutical industry to share their latest insights into the research of aging.
Alex, you are wearing the drug discovery hat in the morning and daytime, and a smaller deep longevity hat in the evening. You are the person to ask this question: Will immortality be achievable in our lifetime?
My answer is clearly – no. Not with the current technologies and not with the pharmacological interventions. I had a very rosy outlook on this question 18 years ago, when I entered the field of biotechnology. With technology progressing exponentially in every field, I thought that longevity must be the next big thing. My expectations were very ambitious. Even in 2014, when we founded Insilico Medicine, I had the impression that longevity escape velocity was just right around the corner. I noticed that this happens very often to the scientists and entrepreneurs who switch from IT into biotech. We all initially think that we can move at the same pace of innovation. However, working with the pharmaceutical industry has made me realize that human biology and physiology is incredibly complex and that pharma is facing many challenges. Just to put you into perspective, it takes about 12 years to discover and develop a novel drug - from the time that you identify a novel target to the time you can place the drug on the market - and the failure rate is around 90 %. So even with a correct disease hypothesis and good molecules in your hands, the success rate is not high. The actual time to develop a drug for novel disease mechanisms from scratch and to bring it on the market may take even longer, it may take a couple of decades. Just look at the progress in Alzheimer’s disease, ALS, and many others – we do not even understand the origins of disease. With many drugs, including one of the most popular drugs on the market discovered 100 years ago, Metformin, we do not understand how it works. And there are many great scientists working in the field. That's why I have become more realistic with time. And please do not misunderstand me, we are working very hard to identify new therapeutic interventions to extend healthspan and lifespan and develop advanced AI-based biomarkers. But the pharmaceutical industry teaches you to be modest and realistic.
Which expectations regarding longevity do you consider to be realistic and achievable in our lifetime?
Many people believe that we are going to cure aging just by throwing money at it. Unfortunately, this is not going to be the case. Of course, we do see a huge tangible progress in the industry. It has never been faster, it has never been more fun and there have never been so many people entering the field. However, it is still not moving fast enough. In order to achieve longevity escape velocity, we need orders of magniture more people worldwide to focus on this field. Currently, there is no sense of urgency in our society when it comes to aging and longevity. Just watch the recent Netflix „Don’t Look Up“ movie and think about aging. Most people are distracted by other attention-grabbing stress factors rather than focusing their attention on biotechnology.
There are still many regulatory barriers and an absence of good disease and aging models. The ability to experiment on humans and primates is not moving quickly enough. We need to utilize every resource in order to accelerate but the regulations are there for a reason. Just a Phase I study, where we test safety in healthy volunteers can take a year. And these volunteers are usually university students, not the elderly, making it very difficult to see any effects of the drug on aging biomarkers. That's why we have to be realistic when formulating our expectations. If we want to experience it within our lifetime, we need to become, as the wonderful CEO of Intel, Andy Grove once said, paranoid to survive. We need to go after aging from every angle and we should not feel safe and count on the others. You should not expect others to solve the problem, but tackle it yourself. That's the target I have set for myself. And nowadays, there are so many resources to learn and to get into the field. There are free online courses, including the courses that I helped develop, to get a better understanding of aging, most recent research advances. The industry needs more people from a diverse set of backgrounds and new ideas and approaches. At the pace the industry is moving now, we should not expect to see longevity escape velocity anytime soon. But we should all try. If you are in IT developing addictive time-wasting video games or an entertainment app, it is a good time to re-think your life and look for ways to get into biotechnology.
Alex, what is your personal secret for solving the problem of aging?
I do not regard it as a personal problem, but rather as a societal and socio-economic problem. In fact, it's everyone's problem. Because of the aging population, the economy is under pressure. We are on the clock. I personally contribute to this problem by developing better diagnostic solutions for aging using AI, identifying new biological targets implicted in aging and age-associated diseases, and developing tools to accelerate drug discovery. We have been working on aging biomarkers for a very long time and my group was the first to publish on deep aging clocks - aging biomarkers developed using deep learning. In 2016, we published the first clock and now, we have more than two dozen. We also develop therapeutics for those clocks. Using different data types of proteomics and transcriptomics, we can define the most important features that contribute to the accuracy of these clocks. Features that can be linked to protein therapeutic targets, and then we seek for novel molecules that hit those targets. In conclusion, we are trying to link those targets and molecules for aging to specific diseases. The development of aging therapeutics is economically still not tractable. Linking them to diseases is a path to place them on the market. So I am basically doing both diagnostics and therapeutics.
Very exciting. While waiting for the right kind of drugs and therapeutics to be on the market, what can each of us do to live a little bit longer?
My first advice is: get educated. A clear understanding of the basic aging processes and the products for diagnostics and therapeutics currently available will help you to make the right decisions. At the moment, there are no clinical protocols for longevity defined yet and their development within the next 10 years is unlikely. So use the things that are already available. Be proactive and get educated. Join the longevity biotechnology industry and make a contribution. For medical doctors, who pursue clinical research or science, our Longevity Medicine Course is highly recommended. Also, a number of industry and science conferences can be attended by the general public. Altogether, my recommendation is to get closely affiliated to the field.
Apart from the aspect of education, what can any individual do for a better life quality and thus, for longevity? What are your health routines on a daily basis?
In my opinion, it is very important to maintain a healthy muscle mass, because that's something that you are going to lose gradually over time. It is critical to do resistance training, which I think is even more important than cardio. Getting enough sleep is fundamental. And as I have mentioned before, stay on top of all the recent discoveries in the aging research field. But I would not put too much hope into diet, exercise and sleep. Do everything in moderation, fast from time to time, and you will be fine. Over the many centuries people tried all kinds of diets and fasting. In fact, most of the world’s religions preach fasting. But we do not see many 120-year old monks, yogis, or athletes. A rule of thumb here is simple – if you can’t see at least a couple abs, time to cut down on callories and exercise. Consider that the current longevity record is held by Jeanne Calment, who has reached the age of 122. She quit smoking at the age of 107 and she has continued to drink into her death. She and most of the other supercentenarians did not follow any fitness, exercise or diet protocol. Clearly, a genetic profile that allows you to be a little bit more resilient can help. And also, a little bit of luck.
So everything in moderation, and the main hope is on the progress in biotechnology. Get educated, get involved, and become the venture capitalist of your life. There is no silver bullet at this time. Not yet.
How important are genes for longevity? Are they defining our lifespan?
Certainly, great genes and predisposition to longevity may increase the probability of longer lifespan. But at this time we can not contol this genetic predisposition.
But what we can control is our attitude and behavior. My main recommendation for everyone is trying to set a very ambitious longevity goal. I am convinced that psychology plays a much higher role than any kind of fitness, diets, or exercise routines. If you maintain a healthy young mindset, you won't give in to psychological aging, which does accelerate physical aging processes. Longevity optimism is a very important skill to develop. Try to outrun the current champion, Jeanne Calment. We need to make longevity very competitive to have the desire to live longer.
But there is nothing to get …
Well, it is not about that. We are also participating at the Olympics to just marginally break the record. It is just a temporary pleasure of reaching the top. So we are not getting anything anyway and we need to cope with that. Unfortunately, that's a fact of life. And humans are, to my knowledge, the only species that do realize that they are aging and dying. That's why we naturally develop psychological defenses against that realization. With aging, we get comfortable with ourselves, it is called hedonic adaptation. In my opinion, you should not be happy with being old, you should try to live longer, and everything else will fall into place. And if you have such a desire, you will have to learn. There is no easy way to achieve extreme longevity. If you want to die early, that's easy.
Alex Zhavoronkov is the founder and CEO of Insilico Medicine, a company which uses AI to discover drugs and biomarkers. Alex is also the founder and CEO of Deep Longevity, which seeks biomarkers of aging and longevity. Under his leadership, Insilico opened R&D centers in six countries and regions and partnered with multiple pharmaceutical, biotechnology, and academic institutions and raised over $300 million from expert biopharmaceutical investors. Since 2012 he published over 150 peer-reviewed research papers, and two books including ‘The Ageless Generation’. He is an adjunct professor at the Buck Institute for Research on Aging.