Nobel Prize-winning molecular biologist Venki Ramakrishnan, in his new book Why We Die: The New Science of Ageing and the Quest for Immortality (Hachette India/ Hodder & Stoughton), says that while we better understand, at a biological level, the causes of ageing and death, we are far from major breakthroughs. With several technology mavens, including Amazon founder Jeff Bezos and Facebook creator Mark Zuckerberg, investing millions in ageing-related research, and many others self-experimenting with supplements and therapies to halt ageing, the field is generating great interest among people of all ages. However, much of this doesn’t yet have the sound backing of scientific validation, says the U.K.-based Ramakrishnan (72). Edited excerpts from a Zoom interview:
Your last book, ‘Gene Machine’, was a memoir as well as your own investigation into ribosomes. What made you focus this time on ageing and longevity?
Humanity has wondered for a long time about why we die and what limits lifespan. We’re probably the only species that knows about our mortality. We know that because we have developed language and ability to communicate and ever since, humans have wondered about mortality. This is an existential question. It is only in the last 50 years that we’ve come to grips with the underlying biology of why we age and what eventually causes death. A lot of things are happening in the field. And at the same time, there’s also an enormous amount of hype in the field because there’s a lot of private investment. There are people who want to extend lifespan. Societies are growing older around the world. So, I wanted to discuss all that and felt there was a need for someone who’s a molecular biologist but who also doesn’t have a vested interest in the field. My work on protein synthesis is related to one of the central causes of ageing. So, you can think of me as somebody who works in an area close to ageing, but I don’t work on ageing myself. That also makes me less, I would say, ideological or biased.
You mention how there’s huge private investment (in arresting ageing) and how several (Silicon Valley) tech billionaires are interested. Is this historically unprecedented?
There are now about 700 companies, start-up companies, which tackle different kinds of longevity research. And, you know, many tens of billions of dollars. People will say that’s a very small fraction (about 1%) of the research enterprise. But I would say, in terms of increase in investment and in absolute numbers, it’s still quite a large amount. Having so many people suddenly interested in ‘solving’ ageing is unprecedented because for a long time, ageing was considered a sort of backwater in science. You know, it was not what molecular biologists really wanted to focus on. I think that has changed over the last maybe 30 or 40 years. Part of the reason is that the (developed) world is facing an ageing population. India is an exception in that it still has a relatively young population. But as life expectancy increases in India, it too will face the same problem that all countries go through as they develop, which is that as people start living longer, fertility rates go down and you’re left with a different (population) distribution. And so, there’s a real need to make sure that people are healthy when they age. If they’re not healthy, it will impose huge burdens on the rest of society because there’ll be an increasing fraction of society that needs care. So there’s a lot of incentive for governments and others to invest in ageing research. It’s not just these billionaires who are afraid of getting old.
There seems to be this obsession with not just avoiding ageing, but paradoxically, trying to be younger as you age. You give the example of Bryan Johnson (American tech-millionaire) who is experimenting with several approaches where he’s doing blood-plasma transfusions, including even from his 17-year-old son. What’s the scientific basis for that?
There’s a semantic difference. Being healthy when you’re old is almost the same thing as being young because you’re eliminating the problems of being old. But in terms of Bryan Johnson, he does lots of things, you know. He spends $2 million a year on anti-ageing measures, including collecting vast amounts of data. It suggests that he’s got some terrible fear of growing old. That’s fine. He’s entitled to doing whatever he wants with his money, right? And some of the things he does are actually based on some real science. It’s just that they’re not proven methods in humans. There have been no clinical trials to show efficacy and safety in humans. But he’s willing to take that risk.
Tech entrepreneur Bryan Johnson wears a brain scan helmet. | Photo Credit: Wiki Commons
Let’s say if we had cures for heart disease, for Alzheimer’s disease and cancer — the top three causes of age-related morbidity and mortality — would that mean a long healthy life where you suddenly drop dead one day? Would that be an ideal state to steer medical research towards?
Possibly, but not necessarily. In the book, I quote the scientist S. Jay Olshansky, who calculated that even if you eliminate all the chronic diseases of old age, you would only gain maybe 15 years, on average, of life. This has to do with the fact that there are natural biological processes that break down and eventually hit against our natural limit of 120. So, to tackle those, you have to tackle the fundamental causes of ageing itself rather than these diseases. I think it’s not clear that you can simply engineer this away. I also don’t know if you can improve healthy life by, say, eliminating many of these diseases, if you would have a sudden decline or whether you would simply postpone a gradual decline, you might have other problems like frailty, your immune system gradually deteriorates, your muscles deteriorate. So, it might happen gradually anyway. The only thing I can say is that there are these examples of super-centenarians, people who live to be over 105 or 110, who apparently will have a very, very healthy life for most of their lives and then rapidly decline before they die. So, at least there are some individuals who have managed this ideal life where you are healthy and then suddenly decline. But how to, you know, sort of make that generally possible in everyone, I think that’s an unsolved problem.
What are your thoughts on cryopreservation? Let’s say our bodies are going to die and we could preserve our brains and transplant them into healthy bodies...
I put it in the same category as Egyptian pharaohs being preserved as mummies because it was thought they were going to come alive at some point in the future. There’s no evidence that cryopreservation works in anything, even in a mouse. It works in very, very small things like cells. We can even preserve larvae of worms and we can preserve, you know, larvae of flies. But as you get larger, even as small as a mouse, preservation itself destroys the tissue. The business of decapitating someone and just preserving their brain is completely in the realm of science fiction. We have no idea how the brain organises its information. It’s not just about connections between neurons but about the state of each neuron and we have no idea how to preserve that.
Would a world where people routinely live healthy lives of 120 or 130 years be a desirable world?
If we all lived to the natural limit of our biology, which is 120 years or so, I would say who am I to argue against it, because we’ve already lived twice as longer as people who lived 150 years ago. I think living extremely long lives, where we want to live beyond the 120-limit, would lead to a weird and stagnant society. We are having a much slower turnover between generations than we did before, so it will be a different kind of society. That’s also assuming that your brain stays sharp and aware, and that’s not a solved problem. The whole problem of cognitive decline and dementia is going to be a very hard problem to solve, even with modern tools. Neurons don’t regenerate. We can regenerate other tissues, like the liver and blood cells. Regenerating the brain is not in the realm of possibility right now. Living with cognitive impairment isn’t desirable and this will impact the kind of societies we live in.
jacob.koshy@thehindu.co.in
