Nicolai Tangen: Hello and welcome to In Good Company. I am Nicolai Tangen, CEO of the Norwegian Sovereign Wealth Fund. Longevity is one of the hottest topics in the world today. Billionaires are pouring money into it. When they were young, they wanted to be rich, and when they are rich, they want to be young. The wellness industry is selling it, and advice on how to live longer is everywhere. So, we wanted to know what the truth is. Is it just hype, and how close are we to becoming immortal? To help us understand, I am joined by Sir Venki Ramakrishnan, Nobel Prize winner in Chemistry, former President of the Royal Society, and author of the amazing book 'Why We Die'. Venki, welcome.

Venki Ramakrishnan: Thank you.

Nicolai Tangen: You start your book with the Egyptian pharaohs, who believed they could transcend death. Why did you start there?

Venki Ramakrishnan: Look, the story of the Pharaohs is very interesting because humans have always tried to avoid death in different ways. Plan A is to just somehow avoid dying. Plan B is to believe that even if you die, your entire body will be resurrected and you will go to some heaven. And Plan C is that even if your body rots, you will have an immortal soul that survives you, and you can enter other bodies, and so on.

Nicolai Tangen: So now, thousands of years later, how close are we to living forever?

Venki Ramakrishnan: I think there is no physical or chemical law that says our lifespan must remain what it is today. I mean, if you look at it today, we can expect to live to 110 or maybe 120 at most. There is only one person who has gone beyond 120. But there is no physical law. That doesn't mean anything can happen. Because there is also no physical law that says we cannot survive in other galaxies in the future, but if you look at the difficulties involved in just going to Mars, you will understand how difficult that is. And so, I put this extreme longevity—living for hundreds of years—in the same category, which is very unrealistic today, regardless of what you hear from the people creating the hype. But before going into depth, we should define what aging is.

Nicolai Tangen: Before going any deeper, tell us, how do you define aging?

Venki Ramakrishnan: Yes, aging, I would say it's the gradual decline in the functioning capacity of our systems. That is, due to the accumulation of damage and changes over time at the molecular, cellular, tissue, and whole-body levels, our body gradually starts to fail to work normally. I, like most scientists, would define aging this way. It shows many symptoms externally, like you don't walk as fast, you are not as strong, and you are more susceptible to infections. There are many external signs, but behind these phenomena is the accumulation of damage in our cells and tissues. And all of this ultimately starts at the molecular level. By the way, you are 74, but I don't see many external signs of aging in you.

Nicolai Tangen: Haha, I'm lucky because I have darker skin and live in a cold climate, which creates a superficial illusion of youth. But if you look inside my body, you'll see that it's actually quite old. But we can talk about that later. Now, it seems like two ideas are getting mixed up, right? Extending life means slowing down the aging process, whereas rejuvenating cells means making old cells young again. So what is the difference between these two?

Venki Ramakrishnan: Okay. Most anti-aging strategies are entirely about preventing damage or slowing down the rate of damage and dysfunction, right? But there is another class of strategies that tries to push cells backward in their development. To understand this, we need to know that a fertilized egg can turn into any tissue in the body, which is what it does, right? In the early embryo, there are many cells, but each of them can become any type of tissue. These are called pluripotent stem cells. But as the embryo develops, these stem cells become specialized. Some cells can only form blood cells, others can only form nervous system cells, and so on. There are many cell types. But this process normally never goes backward, except in real life reproduction. When older parents have a child, the clock resets to zero. A baby born to a 40-year-old woman is no older than a baby born to a 20-year-old woman. So at some point, resetting happens. And this resetting is highly selective. Cells that are damaged or don't develop properly don't end up forming a baby. So this is the process people are trying to reverse. The first proof of this came when John Gurdon took a skin cell from a frog, extracted its nucleus, and put it into an egg cell, developing a completely new frog that was a clone of the original. This showed you could reset the clock of a skin cell. Later, Shinya Yamanaka showed that putting just four genes into almost any cell could revert it back to the pluripotent stem cell state. People are trying to apply this logic. Of course, you don't want all your organs to turn back to pluripotent stem cells because that would cause chaos and tumors. But people are asking: can you push the program back just a little bit, so that the cell maintains its identity—a skin cell remains a skin cell, a muscle cell remains a muscle cell—but its age is set back? This is called partial reprogramming to reverse the aging clock, and it is a very exciting field. But how long it will take to make this safe and effective in humans remains unclear.

Nicolai Tangen: By the way, what is going on inside our cells as we age?

Venki Ramakrishnan: Well, many things happen. One thing is that our molecules start getting damaged, and a main cause of this damage is DNA damage. When this goes wrong, it has two consequences. First, the cell senses this damage and pushes itself into a program called senescence. There, it normally stops dividing and functioning and actually starts releasing inflammatory compounds. Early in life, this is a way to prevent cancer, because if you have damaged DNA, you don't want that cell to keep dividing, as it could mutate and become a cancer cell, right? So it's a way for the body to get rid of damaged cells. But if this damage persists, it can also alter the genes that are part of our genetic program and cause dysfunction. So molecular damage can cause systemic disruption. Another consequence of this damage is that the cell cannot control itself properly. In our cells, we have organelles called mitochondria which have their own DNA, but they also work with the rest of the cell, and these can be heavily damaged too. As you can see, damage is caused by all kinds of things, from exposure to chemicals. Even water alone can damage DNA. This was discovered by Tomas Lindahl, for which he received the Nobel Prize. So just the process of living causes damage. But we have repair mechanisms that keep fixing it. However, after a certain age, damage starts to accumulate. Those mechanisms are never perfect.

Nicolai Tangen: Speaking of this, a century ago most people died at 50 or before, and today the average age is around 80. You mentioned one person went beyond 120. So why hasn't that maximum limit moved further?

Venki Ramakrishnan: Right, we have to distinguish between average lifespan and maximum lifespan. What we have done over the last century is drastically reduce early and mid-life mortality. Through clean water, sanitation, vaccines, and antibiotics, we have allowed the vast majority of people to live to old age. However, we have not changed the fundamental rate of aging. We have simply allowed more people to reach the edge of the cliff. The reason the limit is around 120 and not higher is that we are not killed by a single cause. We are a collection of complex, interdependent systems, and by age 120, almost all systems are failing at the same time. It's like an old car where the engine, brakes, and gearbox all fail together; even if you fix the headlights, the car won't run.

Nicolai Tangen: So, which organ actually ages the fastest?

Venki Ramakrishnan: Haha, many people want to know which organ fails first. Actually, the answer is different for everyone. For some, it might be cognitive decline in their brain; for others, it could be the heart, kidneys, or immune system failing first. Our body is a network of complex systems, much like a chain whose strength is determined by its weakest link. If your immune system ages fastest, you might die of a severe lung infection before other organs fail. If your cardiovascular system is the weakest, you might succumb to a heart attack. So there is no single 'first organ to age', only the weakest link.

Nicolai Tangen: Talking about these markers or hallmarks of aging, which ones are the most important?

Venki Ramakrishnan: Scientists have identified several key 'hallmarks' of aging. The most crucial include genomic instability, where our DNA keeps getting damaged and repair slows down; telomere attrition, where the protective caps at the ends of chromosomes shorten with each cell division; epigenetic alterations, where the switches that turn genes on and off malfunction; loss of proteostasis, leading to an accumulation of misfolded proteins; deregulated nutrient sensing, meaning cells cannot manage energy properly; mitochondrial dysfunction, where the cell's powerplants fail; cellular senescence; and stem cell exhaustion, which prevents the body from regenerating. These hallmarks are all interconnected.

Nicolai Tangen: How is AI changing the pace of new discoveries?

Venki Ramakrishnan: AI is having a revolutionary impact on biology and medicine. The most famous example is AlphaFold, developed by Google DeepMind. In the past, determining the 3D structure of a single protein took months or even years of hard experimental work. Now, AI can predict the structure of almost any known protein in seconds with incredible accuracy. This has dramatically accelerated our understanding of the cell's molecular machinery. In longevity research, AI helps screen thousands of compounds to find drugs that repair cells or clear senescent cells, compressing decades of exploration into years or months.

Nicolai Tangen: What can you do in your lab now that you couldn't do before?

Venki Ramakrishnan: We can now use AI tools and advanced imaging to visualize how giant molecular machines like the ribosome interact with drug molecules in real time at atomic resolution. We can simulate molecular changes and rapidly design antibodies or small molecules to block disease processes. This high-throughput, computationally driven design was unthinkable ten years ago when we had to do massive trial-and-error experiments.

Nicolai Tangen: Why are billionaires suddenly pouring billions of dollars into longevity research?

Venki Ramakrishnan: Well, if you look closely at these billionaires investing in longevity, they share a common trait: most are aging men. When they were young, they did everything to accumulate endless wealth and power. Now that they have it all, the one thing they cannot stand is the idea of aging and losing it just like everyone else. It's an ultimate fear of death and a desire to use money to conquer nature. They fund companies like Calico (backed by Google) and Altos Labs, hiring top scientists to study how to reverse aging. But this has also generated a massive amount of hype.

Nicolai Tangen: What are your thoughts on companies like Calico, Altos Labs, and longevity pioneers like Bryan Johnson? How much of it is science, and how much is hype?

Venki Ramakrishnan: I think we need to distinguish basic science from commercial sales. Companies like Altos Labs employ brilliant scientists doing serious research on epigenetic reprogramming, which could eventually yield breakthroughs for diseases like Alzheimer's or macular degeneration. But that is different from commercial longevity therapies. Most things sold in the wellness industry—like resveratrol, NAD+ boosters, or extreme supplement regimens—lack rigorous clinical proof in humans. What Bryan Johnson is doing is a highly expensive personal experiment, tracking and trying to optimize every biomarker, but it is not a universally applicable or scientifically proven pathway.

Nicolai Tangen: So, what are the actual big breakthroughs in the field right now?

Venki Ramakrishnan: The most solid breakthroughs are in our understanding of fundamental aging pathways, such as caloric restriction. Scientists found that limiting calories triggers autophagy, where cells clear out damaged parts. This extends lifespan in animals. Drugs like metformin and rapamycin show promise in mice and are undergoing clinical trials. Another is partial reprogramming—though only successful in mice so far and carries cancer risks, it proves the cellular clock can be rewound.

Nicolai Tangen: If we gave you 3 billion dollars to spend on any research you wanted, where would you put that money? What is the most promising part?

Venki Ramakrishnan: I would direct most of it toward targeted basic cell biology, specifically protein folding, DNA repair fidelity, and mitochondrial quality control. Many aging diseases, like Alzheimer's, are fundamentally due to protein misfolding and accumulation. If we can find ways to improve the fidelity of the cell's repair mechanisms or understand why some species like the naked mole rat live ten times longer than other similar rodents, we would have the real keys. I would also fund rigorous screening of active factors in parabiosis.

Nicolai Tangen: There is research into differences between young and old blood. What is in young blood and what is in old blood? Can you expand on that?

Venki Ramakrishnan: Yes, this comes from experiments called parabiosis, where scientists surgically connect the circulatory systems of a young mouse and an old mouse. The results were shocking: many tissues in the old mouse, like muscle and brain cells, were rejuvenated, while the young mouse showed signs of accelerated aging. This indicates there are systemic factors in the blood. Young blood has growth factors that promote regeneration and damp down inflammation, while old blood is filled with inflammatory cytokines from senescent cells. Scientists are trying to isolate these specific proteins to develop therapeutics, rather than directly transfusing young blood into humans, which carries massive risks like immune rejection.

Nicolai Tangen: So for ordinary people who want to add a few years to their lives, where should we start based on science?

Venki Ramakrishnan: The answer is surprisingly simple and traditional. You don't need to spend millions on unproven therapies. You just need to do three things: get enough sleep, eat in moderation, and exercise regularly.

Nicolai Tangen: Let's start with sleep. How much do you sleep, and why is sleep so critical for aging?

Venki Ramakrishnan: I try to get about 7 to 8 hours of sleep. When we sleep, our brain goes through a clearance process. Cerebrospinal fluid washes through the brain during deep slow-wave sleep, clearing out metabolic waste accumulated during the day, including beta-amyloid, which is linked to Alzheimer's. Sleep deprivation also triggers chronic systemic inflammation, speeds up cellular aging, damages the immune system, and disrupts hormone levels. So, sleep is the most indispensable time for self-repair.

Nicolai Tangen: What about exercise? What kind of exercise do you do?

Venki Ramakrishnan: I cycle regularly, hike, and do some strength training. Exercise is the most scientifically proven anti-aging medicine we have. It doesn't just build bones and muscles, preventing sarcopenia, but more importantly, it stimulates mitochondrial biogenesis. Working out forces cells to burn energy, driving mitochondria to renew themselves and function more efficiently. It also improves cardiovascular health, lowers blood sugar, regulates insulin sensitivity, and promotes neurogenesis.

Nicolai Tangen: Speaking of Norway, cold plunges, saunas, and temperature alternating therapies are very popular now. What do you think of these habits?

Venki Ramakrishnan: For saunas, there is decent scientific evidence showing that regular sauna use improves vascular elasticity and cardiovascular health, mimicking the effects of light aerobic exercise. But for cold plunges, the evidence is mostly short-term, relating to adrenaline rushes, pain relief, and reducing muscle inflammation. As to whether it actually slows aging or extends lifespan in the long run, there is no solid, long-term human data. It is mostly a wellness trend, and we should view it with skepticism.

Nicolai Tangen: If we do succeed in drastically extending human lifespan, will society actually be better? What are the costs?

Venki Ramakrishnan: I have deep concerns about that. First is inequality. If longevity technologies are developed, they will likely be highly expensive and inaccessible to most. We could end up with a nightmare of biological inequality, where the rich not only have wealth but also longer, healthier lives while the poor remain short-lived. Second is the stagnation of generational turnover. Human progress relies on new generations bringing fresh ideas and replacing the old. If older generations—especially leaders at the top—never step down, society will freeze, and new science, culture, and progress will stall.

Nicolai Tangen: Let's talk about your background. You started in physics. Why is physics a good starting point for a career?

Venki Ramakrishnan: Because physics is a highly rigorous discipline that trains basic rationality. It forces you to look for first principles and requires strong quantitative analysis and mathematical modeling. Once you master the physicist's way of thinking, learning to strip away complexity to find the core, you can apply this sharp analytical tool to any field—whether transitioning to molecular biology like I did, or going into finance, computer science, or engineering. It gives you the lens to see the essence of things.

Nicolai Tangen: With the rise of AI, do you think having a broad curriculum is more advantageous than narrow specialization?

Venki Ramakrishnan: I strongly believe that in the age of AI, a broad, interdisciplinary education has an incomparable advantage. AI excels at surpassing humans in narrow, well-defined domains by processing vast amounts of specific data. If your education is too specialized, you risk being easily replaced. In contrast, a broad curriculum fosters human-unique skills like associative thinking, critical analysis, and creative problem-solving across domains. We need to understand connections between disciplines, know how to query AI, and transfer knowledge horizontally.

Nicolai Tangen: As the former President of the Royal Society, what did you learn from that experience?

Venki Ramakrishnan: That experience taught me how difficult and crucial communication between science and the public is. Scientists cannot hide in ivory towers. We must explain complex science to the public, especially on contentious issues like climate change, vaccine safety, AI ethics, and gene editing. If science loses public trust, progress stalls, and pseudoscience fills the void. We must provide objective, rigorous scientific evidence to policymakers while maintaining scientific independence.

Nicolai Tangen: Many longevity studies also mention mindset. Do you think gratitude helps us live longer?

Venki Ramakrishnan: I do think mindset, especially gratitude, has a positive physiological basis. Feeling grateful and maintaining an optimistic attitude can significantly reduce stress hormones like cortisol. We know chronic stress is a major trigger for systemic inflammation, which damages the immune system and causes cardiovascular disease. By reducing psychological stress through gratitude, you are essentially decreasing the molecular damage load on your body.

Nicolai Tangen: As a final question, are you afraid of death?

Venki Ramakrishnan: I am not afraid of being dead. After all, I didn't exist for billions of years before I was born, and there was no pain in that. So being dead won't be scary. But I do feel cautious about the process of dying. I hope to avoid a long, painful decline and a loss of dignity. This is why we study aging and longevity: our goal is not just to add years to life (lifespan) but to add life to years (healthspan), so we can live with health and dignity until the very end.

Nicolai Tangen: Haha, you just made a Freudian slip. You said 'if I die' instead of 'when I die'. Does that mean deep down you believe in some continuation, or are you hoping for immortality? Do you believe in an afterlife?

Venki Ramakrishnan: Haha, no, I don't believe in an afterlife. I don't believe in a soul surviving after death. That 'if' was just a slip of the tongue, maybe a Freudian slip of wishful thinking, but it has nothing to do with a belief in the afterlife. Thank you, it was great talking to you.

Nicolai Tangen: What an incredible experience it was to talk to you. Thank you so much for taking the time.

Venki Ramakrishnan: Thank you so much for having me.