Why We Can’t Age in Reverse (And Why We Might Not Want to Anyway)

Ashwin Rodrigues
·20 min read

Michael Houtz; Getty Images

For anyone overwhelmed by the discourse around longevity and the seemingly constant “breakthroughs” in the quest to vanquish the march of time, Nobel Prize–winning biologist Venki Ramakrishnan’s new book Why We Die: The New Science of Aging and the Quest for Immortality is meant to help make sense of it all. It seeks to provide, as Ramakrishnan puts it, a “hard, objective look at our current understanding of aging and death.”

Because of the natural human fear of death—and its inevitability—the appeal of Why We Die is evergreen. But the book also comes at an opportune moment for a longevity reality check: A few days before it was published earlier this year, David Sinclair, perhaps longevity medicine’s most visible exponent, stepped down from the Academy for Health and Lifespan, which he founded. Scientists had resigned in droves from the academy because Sinclair had claimed his veterinary supplement company Animal Biosciences had reversed aging in dogs. One former colleague, Matt Kaeberline, went as far as describing Sinclair's behavior as that of a “snake oil salesman." (Snake oil seems to be the hottest supplement in longevity right now. Even Dr. Peter Attia, who wrote Outlive: The Science and Art of Longevity, told the New Yorker the term longevity itself “just smells of snake oil.”)

Why We Die gets back to basics. Ramakrishnan, a former president of the Royal Society, goes to great lengths to back up his modest take, which boils down to: There’s some exciting research being done, we’re far from being able to “reverse aging,” and we should wonder if that’s something we actually want to do. He points out that cell death, for example, can also be seen as a mechanism to protect against cancer—so a compound that reverses aging at a cellular level isn’t necessarily a good thing.

Ramakrishnan also covers some of the interpersonal rifts in the space between aging researchers and the people he calls “immortality merchants.” Though Ramakrishnan identifies a large part of gerontology (the study of aging) as important, legitimate work, he takes issue with the people he feels have monetized our fear of death by keeping a fluid relationship between their marketing and underlying science.

For any casual Attia or Huberman listener, some key terms will be familiar: TOR pathways, sirtuin, resveratrol, and all types of -phagy’s. But the windup does not end with a pitch or a protocol. In Why We Die, Ramakrishnan tempers our expectations on the longevity hype, and wonders what would happen if the most optimistic claims actually came true.

He spoke with GQ to talk a little more about the hype around life extension and what might actually help you live longer.

GQ: It seems like there's a groundbreaking development in the longevity space about twice a week.

Venki Ramakrishnan: Part of it is that there's human anxiety about aging and about death. A lot of people actually might be willing to accept death—although you never know until you're close to it—but they really dread to be incapacitated, the decrepitudes of old age. And so a lot of the anti-aging industry tries to monetize that anxiety by selling them supplements or this, that, or the other. Some of the supplements might do something useful, others probably not.

Many of these supplements might have promise on some mechanistic level, but the long-term research hasn't been done.

Correct.

And some people are just like, Hey, I'm gonna run an N-of-1 long-term study on myself.

Exactly. And some people will openly say that. Bryan Johnson says, “I'm a longevity pioneer,” and he's trying all of these things.

That I find very interesting, because I’m like, OK, you're running an N-of-1, but how are you controlling for all of these variables?

It's a completely unscientific study. Even if Johnson lives for extraordinarily long time, it's simply because he's rich and has very good medical care. We have no idea how much of the intervention actually worked.

How would you would describe the philosophy and approach of gerontology versus the longevity and anti-aging space?

I would have thought they're both the same. Gerontology is the study of what happens as we age. And anti-aging is simply an application of that: They're trying to intervene in those processes. So I wouldn't make a strong distinction between the two.

Most of the sane end of the spectrum, and certainly most of the governmental support—the NIH, the Medical Research Council, and so on—their support for aging research is really to ensure that people try to stay healthy as they get older. And that's a serious social issue, because we're getting older—societies are getting older. When Social Security was instituted, the median age was below 65. More than half of people wouldn't even reach Social Security age. And now, people are living well over 15 years, maybe two decades, beyond Social Security age, so there's an issue of how can you keep older people healthy? And also, how can you keep them independent? Because you don't want them to be dependent. And then, how can you keep them productive? So those are all questions about what you can do about aging, the processes of aging, and the diseases connected with aging.

So the philosophy in the community shifted between tackling individual diseases like cancer, diabetes, dementia, et cetera–which, of course, we have to tackle. But maybe they felt if you tackle the underlying causes of aging, then you would help with all of those things, because all of those things get worse—the chances of developing it get worse—with age. I would say that most sane people?…that's what they're aiming at.

Then there's this highly optimistic or aggressive end of the spectrum, [those] who just want to "solve" aging, or they want to "abolish" aging, or indefinitely postpone it. They're very prominent, but for most of the community, that's not what it's about.

To that point: When you were talking about aging as a societal issue, and something that governments have a real financial interest in figuring out— that's an interesting motivation. And then you have the very individual motivation of billionaires who are trying to recapture the youth that they wasted building their fortune.

[Laughs] That's a good phrase.

You put it better in the book, writing “when they were young, they wanted to be rich, and now that they’re rich, they want to be young.”

That's actually a paraphrase of a fellow journalist of yours. A guy named Antonio Regalado. He often writes for the MIT Technology Review, and I got it from one of his articles. I've cited him. I've reworded it, but that's his basic idea. When they were young, they wanted to be rich. And when they're rich, they want to be young.

That chase has a knock-on effect: Even if you look at popular health podcasts, some of these longevity findings, like when something new comes out on NAD or whatever it is, it's discussed.

Absolutely. And NAD precursors, like NMN [nicotinamide mononucleotide], or NR [nicotinamide riboside], there are two main precursors that are being marketed. They have the sales that are $280 million a year and expect it to go to a billion dollars by 2030, so it's highly monetizable. But anything that can be monetized always gets a lot of press, and nobody wants to wait for the human clinical trials to ask, Is it really improving?

First of all: One thing that field has a problem with is defining how to measure aging. Because if you only measure it by mortality, you have to wait an awfully long time for clinical trials—20 years to see any effect, right? Or even longer. So what they do is they want to have other markers like blood markers or epigenetic markers.

There are a bunch of molecular changes that occur with age. But what the community has to decide is to agree on a set of markers that everybody says, Okay, this set of markers is measuring aging, and these are the criteria for how we would measure aging. But aging is somewhat complex. Somebody could be high in one marker, but low in another marker; so what does that mean? And people now also monetize markers, they sell tests to determine biological age for $500 or $1,000 a pop? You could give them a sample of your blood, and they tell you, oh, your biological age is this. And there's a bit of snake oil in that, because these markers work on a population level.

We know that a population as a whole develops epigenetic changes with age. But [for] an individual, a single marker can't actually tell you—and also, different parts of an individual may have aged to different degrees. Your liver may be older than your kidney or your lung. If you're a smoker, maybe your lung ages very fast. These things need to be sorted out by the community before that's ready.

But getting back to the supplements and these treatments, if they can agree on a set of markers, and use that to measure aging, then they can measure what is the effect of all these various therapies, and see how effective they are, et cetera. And some people are trying to do that, but others are jumping the gun and just selling their stuff based on some animal trials and preliminary reports, and some very preliminary studies.

Something similar to the biomarker tests that I've seen is continuous glucose monitors being used in this way. The technology is ahead of the education, especially where people promoting a ketogenic diet will put it on, and then they'll eat bread and be like, “Look! It spiked. That means bread is bad.”

I'll give you a quote from a famous guy. He said it was “a way of separating money from the worried well." He said that the effect of wearing a CGM monitor 24/7, giving you feedback on the effects of every mouthful you eat on your glucose level is likely to be sizable and have a substantial influence on behavior. He said the worried well—the upper-middle classes—are ripe for financial exploitation of this kind. And he said that the CGM device is great for diabetics because they have to know how to control their glucose and when to take insulin and things like that. So it's a very useful tool for diabetics, and allows them to have much better control over their blood sugar. But for ordinary people? It's just crazy. It's just a waste of money.

It's a medical technology that became a consumer gadget.

Yeah, and making lots of money: They can sell hundreds of thousands of these devices with minimal real benefit.

There's this trickle-down interest in longevity and whatever you can do to pursue anti-aging, even at the normal person level, via podcasts. I'm thinking of the Huberman Lab podcast, and Peter Attia's podcast. They aren't singularly focused on longevity, but it's obviously a large part of their interests. I'm curious if (a) you listen to them and (b)—

No, I have not listened to them. I've taken a look at Attia's book, Outlive, it's a big bestseller. It's highly prescriptive. He says, You've got to do these 10 things that'll get you to be able to do this, this, and that. And he's also a very big fan of rapamycin, beyond what's clinically tested. I don't want to say too much except: He's also involved in pushing advice, and various supplements and so on. I wouldn't want to say anything too directly, because I don't want any lawsuit on my hands. But I would just say that's a very different approach from mine, which is to just simply look at the biology and point out: What are the limits of our understanding today? And what do we need to progress beyond to something that's applicable? I'm not saying that rapamycin is never going to be useful, but I think they need to establish long-term safety, long-term efficacy, dosing, all these things. Maybe it's not the best compound, maybe you need a different compound that also inhibits TOR, but in a safer way. So I think there are a lot of issues there.

From the academic and research perspective, is this focus on longevity influencing what gets funded—taking money from other places?

It's not a huge fraction. The amount of money going into longevity has really exploded, but it's still a very small fraction of the overall research budget. So I'm not too worried about that. As we discussed, it is a real social issue that societies need to address. So I am not against longevity research; I think it's a very good thing to have. I think we need to have serious longevity research and really take a look at what will improve health best in old age: What are the interventions that are the most effective and the safest in old age?

One thing that is influencing it is the amount of private money going into longevity research, and how some of that private money is actually attracting some of the best scientists away from academia into these private institutes which are potentially for-profit institutes. That creates certain conflicts of interest, and also influences the agenda slightly about turnaround times, speed, priority of problems; all of those things can be influenced once you have private investors backing things. I think there really is a danger that longevity is being influenced by private money, but the public side I think is okay.

You urge people in the book to exercise a bit of skepticism or caution when they see a study go viral in the news.

One of the purposes for the book is saying that aging is complicated and involves a lot of biology, and it has to do with how we evolved. So what I've done is walk the reader through, in hopefully a very accessible way, all of the underlying biology for why we age and why we die. And the goal is, first of all, that understanding the biology also gives them the tools for how to live. What should they do if they know these are the things that cause aging, and these are things that can help. It's not a recipe book, like some of these aging books that say "Do this, this, and this," but rather say, this is what happens. So you can take it in your hands to do the right things to help the process and be more healthy. So that's the first thing.

The second is giving them the understanding that the biology of aging means that every time they come across these articles, they can have a mental framework now of how to evaluate an article. If it's NMN, then they know what NMN is doing—they've read about it, so they can go back to the book and look it up. And so they can have a mental framework to evaluate new findings and see if they're hyped, or if there's something there. And if there's something there, is it ready for prime time? Or what other work needs to be done before it's useful. It's really to empower the general reader.

Obviously, gerontology has been around for a long time. Was there a tipping point where the longevity field changed?

Well, there have always been these extreme-longevity advocates for a long time. That's not new. It's not new in human culture, either. There was always the Fountain of Youth, and things like that. This is just the latest act in a long-running play. But what has changed is that there's now serious science. I would say 50 years ago, aging was considered a slightly backwater field—maybe even disreputable. Mainstream biologists didn't really want to go into that.

And then because of social pressures, because of social requirements, because the NIH and all these government agencies said, Hey, we have to do something about this, we need to understand the biology, then serious biology started getting done. It still has its shaky science, but lots of fields, especially which involve human health, have that, and I would say there is quite a lot of rigorous science going on in the aging field.

Do you have concern for the average person really focusing on optimizing everything for longevity? Beyond the reasonable things like eating well and moving around.

[Longevity advocates] would say, if you talk to them, they would say longevity is really about health. It's the health that makes them live longer. And so that's not a bad aim. I don't want to be too hypocritical, because I'm taking two or three anti-aging medicines, as I pointed out in my book: I'm taking blood pressure medicines, I'm taking statins. [The third medication is aspirin.] Now, you could say I could've tried to control that purely with diet and exercise. And I did try, but it eventually caught up with me until my doctor said, “Look, I would really advise you to go on statins and take blood pressure medicine, or you're gonna get a stroke or a heart attack.”

If somebody came with a pill and said, “Look, this is going to give you 10 years extra of healthy life,” now, most of us will take that, right? Who would want to become sick and die right away instead of being healthier for 10 years? So we can't be too hypocritical, but I think the focus on radical life extension is completely misguided.

You mention the rushed rollout of social media and AI, and the impact that's had on our world. Are there any nascent technologies that give you some optimism?

AI has a lot of potential to do good in science. In my field, it's having a pretty major impact in predicting protein structures; it could be useful in genomics, and pattern recognition in cells, and so on. I can imagine AI being potentially very useful, but AI is so hyped and, unfortunately, the biggest use of AI is going to be in extracting more money from the consumer, and that's a problem. The priorities, especially in Silicon Valley, are not well-aligned with what is good for the consumer or good for society. Maybe we may think it's good for the consumer: Okay, we can connect with our friends, I can talk to you online, and it's all due to computer technology. But it also has a lot of downsides: social isolation, the spread of disinformation. The problem is that these people in Silicon Valley, especially, but just generally tech people everywhere, tend to jump in without thinking of all the potential consequences. If you go slowly, you can deal with consequences as they arise. If you just rush out stuff, then things happen that you're not in control of.

One problem with aging is that, if they make big breakthroughs—I'm not saying they will—but let's say we all start living to be 95, 100. Everybody just starts living longer. It’ll change society in many ways, and we need to be prepared for that. How do we deal with society where people are older? What about intergenerational fairness? What about turnover? What about regeneration? What about economic disparity? The rich already live 15 years longer or more than the poor, and they live more of their lives healthily, much more of their lives healthily. So the poor are not only living shorter lives, but they're spending more of it in poor health. So now, if you have even more disparity, then you can see how it would really diverge, because the rich will accumulate power. And as they get older, they'll accumulate even more wealth, pass on more wealth to their offspring. And you can just have this sort of two-tier system. I think people need to be aware of these things.

I'm curious if there's anything beyond eating well and exercising that you think—

Sleep. Americans always seem to forget sleep, but sleep is very important for repair and maintenance and so on. The other things I didn't mention is that simple checkups for blood pressure, blood markers like cholesterol, lipid, hemoglobin, and other inflammation markers, markers for diabetes. Those are all very important. And if people catch those early, there are useful interventions—like how I'm taking medications for blood pressure—that can really allow you to live a healthier life when they're older. I mean, if you are a stroke patient and you've recovered, your life is still not as good as if you'd never got the stroke. And same with a heart attack.

Those are very obvious measures which are already available. I didn't talk about the social markers, which is being connected socially, having a network of friends and support and regular social interactions, and having a sense of purpose in life. Those are also quite important for healthy aging. So, there are a number of things we can do, but not easily—if you're poor, all of these things are harder to do. The poor don't have time, and they can't eat very good food, whatever cheap food that they can get; they don't have enough time to exercise or don't have a place to exercise. And they often don't get enough sleep, they're working two, three jobs at the same time. So all these things are easier for rich people than for poor people. And so how do we as a society make it more equitable? That's an issue.

I have to ask: Why do we die?

Well, that too is interesting. So while we're alive, millions of cells is us are dying all the time, we don't even notice it. And some of them have to die because they're part of the normal function of living. So they're programmed to die at certain points. At the same time, when we die, most of our cells are still alive, paradoxically. In fact, entire organs are alive—you can donate organs for transplant patients.

So what does it mean when we die? Well, we're not talking about cellular death. When we say humans dying, we're talking about the inability to function as a coherent, conscious individual. And that means we get a series of damages, a series of defects that build up with age. And at some point, it affects a critical function that leads to critical systems failure. For example, if you get really frail with old age, you get heart failure; heart failure will then lead to loss of blood to the brain, the brain will stop working, and then you won't be able to function as an individual. It's this inability to function as a coherent whole—that is how I define death.

This interview has been edited and condensed for clarity.

Originally Appeared on GQ

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