ANTI-AGEING is big business. From books encouraging diets such as intermittent fasting to cosmetic creams to combat wrinkles, a multibillion-dollar industry has been built on promises to make us live longer and look younger. But how close are we really to extending our lifespan in a way that gives us extra years of healthy life?
, a molecular biologist and former president of the UK鈥檚 Royal Society, is the latest to tackle this question. He has spent 25 years studying the ribosome, which is where our cells make proteins using the information encoded in our genes, at the MRC Laboratory of Molecular Biology in Cambridge, UK.
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In his latest book, , he goes on a journey around the cutting-edge biology of human ageing and asks whether it will be possible to extend our lifespan in the near future.
He talks to 快猫短视频 about the recent breakthroughs in our knowledge of what causes ageing, how close we are to creating therapeutics to combat it, and the potential consequences if we succeed.
Graham Lawton: What inspired you to take a break from a hugely successful career researching how cells make proteins to write a book about ageing?
Venki Ramakrishnan: Two things. One is that the translation of genetic code into proteins affects almost every biological process, and it turns out to be central to many aspects of ageing.
The other reason is that we have worried about ageing and death ever since we became humans. For most of our existence as a species, there was very little we could do about it. But because of the tremendous advances in biology over the past few decades, we now have tools and a level of knowledge to think about what causes ageing and what we could do to either ameliorate it or postpone it.
At the same time, there鈥檚 a huge amount of hype in this field. I thought that, as a molecular biologist who understands the broad field while not being in it, who doesn鈥檛 have an agenda or any companies involved in ageing, I was perfectly positioned to take a very hard look at what鈥檚 going on and ask: what are some of the real things we know about ageing and what are the prospects for the future?
Do you think we fully understand the main causes of ageing?
No. Ageing occurs at every level, from the molecular to the cellular to the organs and the entire body, and it has multiple causes that are highly interconnected. Cause at one level can influence cause at a more basic level and vice versa. If some entirely new aspect of ageing were to come about, I don鈥檛 think the researchers would quibble.
But we understand it enough to start thinking about interventions?
Yes, I think that鈥檚 a fair comment. The idea is that a cell doesn鈥檛 want to spend too many resources trying to prevent ageing because it comes at a cost, and it鈥檚 not worth it if you鈥檙e going to die anyway, such as by starving or being eaten by a predator. Our life expectancy has doubled over the past 150 years, so we encounter all these diseases of ageing that, in the past, very few of us would have encountered. As we start to understand the biological basis, people are trying to intervene.
What do you see as the most promising avenues for interventions against ageing?
One very exciting area is stem cell regeneration and cellular reprogramming. Stem cells and regenerative medicine are already established areas with a lot of promise and some people are segueing into anti-ageing research. The idea is to reprogram cells so that you can perhaps reverse them back to an earlier stage so they鈥檙e capable of regeneration. But it鈥檚 early days.
What other approaches are there?
Everybody agrees DNA damage is a fundamental cause of ageing, but so far [work on] DNA repair, and therapeutics targeted at that, has been mostly to address cancer rather than ageing.
But there are people working on telomere loss. Telomeres are the ends of our DNA strands. When you replicate DNA [during cell division], you start losing the ends. If you kept losing the ends, you would start going into the part of the chromosome that codes for important information.
There鈥檚 an enzyme, telomerase, that adds telomere sequences every time there鈥檚 a replication, but it turns out we shut off telomerase in most of our cells, except for certain cells that have to live for a very long time, like stem cells. Many of our cells, like our skin cells and hair cells, have often lost telomerase, and so the question is, could you reactivate telomerase and regenerate these tissues? There are people who are studying that and there鈥檚 some initial promise. I would say [reactivating telomerase] is probably most likely to help with where you have telomere loss, and only after that will we know whether it鈥檚 a general thing against ageing.
Another approach involving DNA damage we are hearing more about is senolytics. What is this?
When you have DNA damage or you have extreme telomere loss, the cell can go to two outcomes. One is [cell] suicide, a phenomenon called apoptosis. The other is to go into a 鈥渟enescent鈥� state where it stops dividing and is no longer functional in the usual sense. But it turns out these senescent cells aren鈥檛 just quietly sitting there 鈥� they鈥檙e secreting inflammatory molecules. These are triggers for the immune system to come and do repairs.
If you accumulate senescent cells, you get inflammation, and if you specifically kill senescent cells, you can alleviate many of the symptoms of ageing that are a result of inflammation. That field is called senolytics, and it seems to be promising.
How does your own specialist area, protein synthesis, tie into ageing?
When you make proteins, they usually fold up into their normal shape and do their thing, but as they age, proteins can unfold. When they unfold, they expose the inside amino acids, which are sort of sticky. And so these proteins tend to aggregate. They鈥檙e bad for the cell, so the cell has lots of ways of trying to deal with unfolded proteins.
What you want to do is shut down protein synthesis. It鈥檚 a bit like if you have a traffic jam, you want to stop new cars from entering. And that鈥檚 what a protein called TOR does. Whenever there鈥檚 stress, TOR will shut down protein synthesis, and this seems to have an effect on ageing because it also turns on degradation and recycling pathways. These metabolic pathways indirectly slow down ageing.
This provides a biological explanation for the long-standing observation that if you calorically restrict animals, providing them with just enough calories to survive, they tend to live longer. Now, of course, nobody likes caloric restriction. Even mice. As soon as you stop caloric restriction, they start gorging on food. I think it might be easier to take a pill that has the same effect, and I joke that this is a 鈥済et out of kale free card鈥�. But actually, we鈥檙e nowhere near.
That is a recurring theme in your book, a reticence to extrapolate from basic science to applications in people.
I just know from much more clear-cut areas how long it takes to go from a basic finding to something that鈥檚 actually useful. Even in the best cases it takes 10 or 20 years. When you take a much more multifactorial and ill-defined process like ageing, this idea that we鈥檙e going to solve it tomorrow is highly optimistic.
The anti-ageing field is also being highly distorted by the injection of huge amounts 鈥� billions and billions of dollars 鈥� of private capital. A lot of it is driven by tech billionaires. They鈥檙e mostly middle-aged men and they鈥檝e got everything in the world. They can buy anything they want. Except youth.
If we can eventually intervene in ageing, do you think people will want to?
I do believe if someday somebody comes up with a pill and says it鈥檒l keep you healthier for 10 years longer with no side effects, who wouldn鈥檛 want to take it? I think we have to be prepared for a potential future where it might be possible, though I鈥檓 sceptical that it鈥檚 around the corner.
But I鈥檓 also optimistic that eventually there may be breakthroughs that will help us overcome some of these barriers. Then we鈥檒l be in a situation where maybe we鈥檒l all be living quite a bit longer. I just don鈥檛 think it will happen in my lifetime or even to anybody born today.
What do you think the consequences will be if we start living longer?
If we all start living longer and we reproduce at the same rate, then the population will start exploding. You鈥檇 have what I think of as a stagnant society. People say, 鈥渙h, but if we had 200 years to live, we would have five different careers鈥�. This is wishful thinking. I think most of our innovation happens when we鈥檙e young. You look at great scientific discoveries, even great works of literature: all were done when people were relatively young. Why is that?
I think part of it is that when we鈥檙e young, we approach life with a freshness and an openness. We鈥檙e willing to challenge existing ideas and dogma. And that gives us a sort of creativity that we start losing as we age. So it鈥檚 not simply a question of staying healthy. I鈥檓 reasonably healthy, but I don鈥檛 think I鈥檓 nearly as creative as I was when I was 40.
I think this is a serious problem, especially if you look at social trends. For example, civil rights or women鈥檚 rights or LGBTQ+ rights. Social changes are often driven by young people. People talk about older people: maybe they鈥檙e not quite as sharp, but they have more wisdom. I鈥檓 sceptical about that too. Often, older groups are driven by conservatism born of nostalgia. I don鈥檛 think that鈥檚 necessarily wisdom.
We already live twice as long [on average] now as we did 150 years ago. Are people today really more creative or more prolific than Mozart or Beethoven or Charles Darwin or Isaac Newton? I don鈥檛 think so.
There are much more pressing issues than slowing ageing. Where would you redirect our efforts?
As someone who grew up in India, I do think this mania to live longer is a First World problem, and I think there are so many more important problems: infectious diseases, chronic diseases, malnutrition, food security, climate change. Those are all much more pressing problems than living 20 years longer.
I do think we should aim to live healthily for as long as we can. But we鈥檝e got to accept our mortality as just part of the grand scheme of things. It is very hard, and I think we鈥檙e deeply evolved to avoid death. It goes against our natural instinct, so it鈥檚 hard work to accept it gracefully.
Graham Lawton is a features writer at 快猫短视频
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See more of Graham Lawton鈥檚 interview with Venki Ramakrishnan at
