Program: Don’t Die: Is Bryan Johnson going to live forever?

Tegan Taylor: Norman, I know you're a bit of a longevity guy. Do you have a number in your head of what you would like to live to?

Norman Swan: No, but I've got a number in my head that I'd like to stay at. 

Tegan Taylor: Oh okay, cool. Talk to me about this. 

Norman Swan: So I had a big birthday a couple of years ago…

Tegan Taylor: I know, you turned 50. You don't have to brag about it.

Norman Swan: Exactly. And a few of us went away, friends and kids and so on, and a friend of mine asked my children how old I thought I was, and they all came up with the same number, which was 50. So I'd be quite happy to stay at 50 for however long I live.

Tegan Taylor: I've got some bad news for you though, Norman, your kids are catching up to you.

Norman Swan: I know. I haven't told them that yet.

Tegan Taylor: Well, that is even more relevant to today's What's That Rash? chat than I expected it to be. 

Norman Swan: Yeah. So have you got an age in mind? 

Tegan Taylor: Gosh, I am lucky to still be young enough that this doesn't keep me up at night quite as long as it does for the over-50s.

Norman Swan: Yeah, wait 'til that brick wall at the bottom of the hill gets closer, you'll want to push it away a bit. 

Tegan Taylor: I'm learning so much from you, maybe I'll never have to worry about it.

Norman Swan: Anyway, that's what we're talking about on today's What's That Rash?.

Tegan Taylor: The podcast where we answer the health questions that everyone is asking. 

And Norman, I did say 'the health questions that everyone is asking', but no one has specifically asked us this question, but we are asking it of ourselves, and I think that there are people who have thought about it before. Today we are talking about a guy called Bryan Johnson. Without any other context, would you know who I was talking about if I just said his name?

Norman Swan: I would, because I've written a book on this sort of topic, so I kind of do know who Bryan Johnson is. 

Tegan Taylor: So if you haven't heard of Bryan Johnson, if you haven't also written a book about living younger longer, by Dr Norman Swan, Bryan Johnson's whole movement is called, effectively, the Don't Die movement.

Norman Swan: And I've just recently read Mel Brooks' autobiography which is very funny, it's laugh-out-loud funny…

Tegan Taylor: It'd wanna be, given his reputation. 

Norman Swan: Yeah. He's just turned 99. Anyway, at the end of the book he's asked the question, you know, how do you explain your remarkable longevity in such good shape? And I think his answer was, 'I didn't die.'

Tegan Taylor: Well, I mean, if it works, it works, right? So, yeah, Bryan Johnson's whole movement is called Don't Die. Basically in 2021 he announced that he wanted to figure out how to continue travelling through time at the normal speed, like a year passes by but his biological age wouldn't change in that time. And Norman, this is a part of the show where I have to issue a trigger warning to you, because we're going to talk about so much longevity stuff today and I know that you are just bursting with information about it, and we are going to have to breeze past a lot of it. Consider this a bit of a primer for about 15 future What's That Rash? episodes.

Norman Swan: Good. Yeah, I'm suitably chastised here and put back in the box. 

Tegan Taylor: No, I don't mean to be in a box, I just want you to know that I see you, I love you, but we are not going to be able to go into anywhere near the amount of depth I know you're capable of today. This episode is going to be longer than usual already, because we've got a lot to unpack here. 

Norman Swan: So we're just focusing on Bryan Johnson and what he does. 

Tegan Taylor: Yes, but I do think it would be useful for you to give us a bit of a primer on biological age versus chronological age, because that's really what this whole thing is about. 

Norman Swan: Yeah, and he's talking about even reversing it, not just staying at the same age, he's talking about reversing it. But anyway, we'll come back to that later. So chronological age is your age according to the day that you were born. So if you were born five years ago, you're five years old today. If you were born 50 years ago, you're 50 years old today. But the question is, is your body 50 years old? And biological age is the age that your body is at, irrespective of your chronological age. And the nice thing to have would be a gap where your biological age is younger than your chronological age, and this is a recipe for living longer. How you measure biological age is, however, controversial.

Tegan Taylor: Yes, and we'll get to that as well. I would like to give props to Bryan Johnson for the branding exercise that he's on here. Now, obviously he wants to live as healthily as he can for as long as he can. He's conscripting other people to join the cause and that sort of thing. But by calling it Don't Die…like, literally if you want to sign up for the mailing list, you put your email in, and then the button to submit says 'Join or Die'. And literally if every single other human who's ever existed in history up 'til now is anything to go by, we will all die at some stage, so I suppose he'll be right eventually with all of us.

Norman Swan: And so he's very rich. He made his money out of a pay company called Braintree, and he's spending a considerable sum of it on himself to try and live longer.

Tegan Taylor: Yeah, so he says he's become the most biologically measured person in history. They basically built an algorithm using all of the science and data (which we will get into) about how you can optimise human biology to keep your biological age as static or as low as possible for as long as possible, and he has basically developed…well, he's asked the algorithm to develop a protocol, and he is adhering to it slavishly. So shall I tell you a

little bit about…?

Norman Swan: Tell us about his happy life.

Tegan Taylor: His happy, balanced, chill life…

Norman Swan: Because this is something where you may not live longer, but you'll certainly feel as if you lived longer.

Tegan Taylor: So basically at its core it's good, it's eat well, it's exercise, it's sleep, et cetera. But he eats pretty much the exact same thing every single day. And also it's not just about what he's eating, but it's also when he's eating. So he has a smoothie in the morning. He has a breakfast at breakfast time, and then he kind of has lunch at 11:30 in the morning, and then that's it for the rest of the day. And then alongside these meals he's also having huge amounts of supplements and some medicines as well.

Norman Swan: So he measures his body composition every day, he does meditation, he fixes up his skin, he treats his hair loss problems with a hair loss drug. And, as you say, he's got this routine, and every night he goes to bed at 8:30.

Tegan Taylor: He talks about, like, your professional full-time job is sleeping. Nothing is more important than sleeping, in his mind. But he has some health markers that he looks at, according to when he's asleep.

Norman Swan: Yes, he is obsessed with nocturnal erections. According to some reports he gives his penis electric shocks, and he takes Tadalafil, which is Cialis, which is in the same family…

Tegan Taylor: It's not Viagra, but it's in the same kind of family of drugs as Viagra.

Norman Swan: Yes, it longer-acting. And he would argue that it either helps his erections or it increases blood flow and maybe improves other parameters of ageing as well. 

Tegan Taylor: Norman, it feels to me that with the rest of his life being so regimented, there may be very little natural joy that he's getting out of it, so let him have this one thing.

Norman Swan: Yeah. I mean, I don't know when he has sex, if indeed he does ever have sex but it's an interesting thing to speculate on. Because some people think that sex…there is one study from Britain which suggests that sex actually does promote healthy longevity.

Tegan Taylor: Okay, well, there's only one way to find out. 

Norman Swan: He's certainly electrocuting his penis several times a night, and measures his nocturnal erections, I think he's almost reached three hours of a nocturnal erection.

Tegan Taylor: That honestly sounds exhausting. 

Norman Swan: Yeah, what do women do with all this information? I don't know. Run for the hills, I think.

Tegan Taylor: I mean, if you get into a long-term relationship with this guy, you're in it for life, by the sounds of it, because he's never going to die.

Norman Swan: Yeah, and he's never going to stop pestering you because he's got to do something with his nocturnal erections.

Tegan Taylor: Okay, so there's that sort of stuff, there's the sleep thing. I know that we're going to talk about biological markers, but the thing that pops into my mind as soon as I read this very regimented regime that he follows is just that, oh, there's got to be a psychological impact to living your whole life so closely…to having such constant measurement, to being basically ruled by an algorithm. He has virtually no agency beyond doing what the algorithm tells him to do.

Norman Swan: Well, he's got complete agency, he's very wealthy, he could decide to do whatever he wants, but he's chosen to do this, and I think because he feels in control, he might just be in perfectly good shape. It would drive you or I nuts if somebody forced us into this routine, but he's made a choice here, and he's got the financial resources to do, in fact, whatever he wants with his life. It's probably worth just going through in detail some of the things that he does so that we can kind of dissect…so he eats a minimally processed diet. So he avoids sugar…

Tegan Taylor: Well, except for all of the supplements, but yes, the food that he eats is minimally processed.

Norman Swan: So one of the things he's on is Metformin, which has changed his regime…

Tegan Taylor: That's a diabetes drug.

Norman Swan: Yeah, so there is some evidence that it slows down some of the aspects of biological ageing. Interestingly he's now not taking Metformin all the time, he's alternating it. He takes things like collagen protein, creatine, prebiotic, inulin.

Tegan Taylor: Some of these things we have talked about on What's That Rash? before. We've talked about collagen and creatine. Inulin is a fibre, it's a prebiotic, it helps promote good gut bacteria. I don't know if you just misspoke, Norman, Metformin, you said it was a supplement. I've always thought about it as a drug. What is the difference between a supplement and a drug? 

Norman Swan: Well, in fact Metformin is a drug, and in fact most of the supplements he's taking are not really supplements, you're taking them as drugs because you're not taking them in the quantities that you would have them in your food, if indeed some of them are in your food. You're taking them in doses which are actually drug doses. And as one longevity researcher says, if it's not going to kill you, it's probably not going to work. In other words, you've got to take it in a drug-like dose, and every drug has side effects, for example. So in fact they're all drugs, and it's misleading to think that they're safe by calling them supplements. And Metformin is definitely a drug used to treat diabetes. It just has these interesting side effects on ageing processes.

Tegan Taylor: Norman, apart from the regimented nature of this, healthy food, we've talked about the evidence for and against some of those supplements before, sleep, exercise is a huge part of his regime as well. But some of the stuff that he's done is a little more out there. I think the biggest headline grabber of the things that he's tried is he literally injected himself with his son's blood.

Norman Swan: Well, his son's plasma, so that's the fluid around the blood cells. 

Tegan Taylor: I mean, apart from the idea of young blood, is there any scientific basis for this?

Norman Swan: There's a little bit, but it's a confusing area. So initially the idea scientifically was (if you can call it science) that young people, young animals, have some sort of thing in their blood which is the elixir of youth. And therefore if you give the blood of a younger person to an older person, they are going to be rejuvenated. And so when you infuse young blood or plasma into an older person, measures of ageing do seem to slow down when you do that. But the interesting thing is that when they gave…well, it was not so much a placebo, a control substance, which was saline, still an infusion, you got the same effect. And it turns out what's going on here is probably a dilution of the toxic substances from senescent cells. These are cells that don't properly die, they hang around, they produce toxic substances which are thought to promote ageing and other problems. So this dilution is thought to dilute these toxic substances that come from senescent cells. So what he's moved on to is total plasma exchange, which is a bit like dialysis, where the plasma exchange syphons off these substances.

Tegan Taylor: So does it take out all of the plasma from his whole body and replace it with saline?

Norman Swan: It's like a dialysis machine…

Tegan Taylor: It's not saline actually, sorry, bear with me, it's albumin or something like that…

Norman Swan: It's replaced with protein called albumin and immune substances. It's used medically as well for some conditions where you can remove substances like antibodies from the plasma by doing this plasma exchange. Anyway, so he's doing that, with no evidence behind it, by the way. Some people believe that maybe it has an effect on dementia, but that's controversial.

Tegan Taylor: The other big thing that he did was gene therapy. 

Norman Swan: So he infused himself with the gene for a substance called follistatin. 

Tegan Taylor: It makes you musclier or something.

Norman Swan: Yeah, follistatin opposes…there's a substance called myostatin which controls muscle growth. So myostatin slows down muscle growth, follistatin increases muscle growth. So he had gene therapy for the follistatin protein, which in theory could enhance muscle growth. And here's the problem with what he's doing, he's doing so much, if it works, what's worked and what hasn't?

Tegan Taylor: There's no control. 

Norman Swan: So he's doing these massive exercises every week in terms of increasing his muscle bulk, so is that follistatin, or is that just doing strength training? So he claims that his follistatin levels went up and his muscle mass went up, which may be true, maybe not. But the philosophical thing here is, is it just Jeff Bezos, Bryan Johnson and a few others who are going to live forever, and so these billionaires are going to be around forever, and the rest of us are condemned to death?

Tegan Taylor: This is my exact problem with this. 

Norman Swan: Go on. 

Tegan Taylor: It's just an insane amount of privilege that it takes to do this sort of thing. And what's the point of one person or a small group of people living for longer if it's this labour intensive? If longevity is the goal…like, one of his catchphrases is 'do what the 25th century would respect', this idea of future focused. Do you think the 25th century is going to respect one or three guys living forever or doing things like…?

Norman Swan: Diplomacy and world peace and controlling climate change? It would be nice to get to the 22nd century, much less the 25th century. And that's one criticism, that they're focusing on stuff that's for individuals, it's not actually the bigger play in terms of humanity and where humanity is going. And it's also about money. So these people who are immensely wealthy are also creating businesses which charge you money to learn from them and develop patented substances that you might take as supplements. So this is about money as well as individual health span. So, I mean, to be fair, they're not talking about longevity for the sake of it, they want to live healthier for longer. 

Tegan Taylor: So part of the way they're spinning money out of this is by creating the supplements themselves, and the other part is the testing part of it. So I want to talk about the evidence for how he's actually measuring this rate of ageing. He calls it the Global Rejuvenation Olympics. Naturally he is number one on the leaderboard. He recognises the world's slowest speed of ageing, 0.48, i.e. he ages at half the rate of time, actual time as it travels. And you can pay to test your own rate of ageing for the low, low price of hundreds or thousands of dollars, depending on which package you get.

Norman Swan: Well, there's a simple way of taking your biological age. Have a look at somebody. If they look old on the outside, they probably are old on the inside, but that's being a bit flip. There have been studies which follow groups of people through life, and have done lots of measurements on through life, so they know what happens to your kidney function, what happens to your heart and your lungs. Lungs are a good measure of ageing, just how much air you can breathe out in a minute, measures like that. So you can measure your kidneys, your lungs, your heart and so on, and there is a deterioration in many aspects of their function through the years. And then they compare that to what's called DNA methylation. 

So DNA methylation is epigenetic, so it's not mutations of the genes, it's changes on the outside structure of the genes, and it's been claimed in the past that there's a steady rate of methylation according to your health or ill health. So methylation goes up, you get more epigenetic effects when you're sicker and when you're ageing faster, and fewer when you're ageing more slowly. 

And what they've done is overlaid the physical measures of these groups of people, and one of them was a group of people who've been followed from birth in Dunedin, about a thousand individuals, so what they show as they get older, and compared that to their DNA methylation. 

So DNA methylation, when it's properly controlled, is probably quite an accurate way of measuring your biological age. However, that doesn't account for the commercial environment where you might send your blood off for DNA methylation, and you haven't got a clue how accurate that is, what benchmark they've used. It's complicated. So when it's done properly, it's probably not a bad measure of biological age, but otherwise it could dramatically mislead you. What if it showed you that you were ageing incredibly rapidly and you were actually doing okay? What sort of conflict would that create? 

Tegan Taylor: But what difference does it make if you're having a healthy lifestyle? Regardless, it kind of…for all that the Bryan Johnsons and his like are trying to control this sort of thing, we don't have a lot of control over this beyond healthy behaviours, right? Like, am I missing something? 

Norman Swan: Well, he would argue that you're missing something. David Sinclair at Harvard, the expatriate Australian who works at Harvard would reckon that you're missing something here. So the argument is that you can't…it's not my argument but it's their argument, that it's hard to imitate the biological processes that slow down ageing at sufficient intensity that it's actually going to make a big difference. Now, I'll come back to the detail in that, but why I don't agree with that is we're actually living longer in good health than we ever have before. So unless something bad happens to you, a lot of people, particularly if you're middle class and well educated and you've got money in your pocket, you're going to live to your 90s and hit your 90s in pretty good shape. So it's already happening, and that's happening through better diet, more exercise, not smoking and so on. 

Now, what they are doing, many of the supplements that they're taking imitate starvation, imitate calorie restriction, and there's evidence from the laboratory that in many animal species if you restrict calories, lifespan goes up, not necessarily healthy lifespan, it's in the laboratory in a sterile environment. Now, there are drugs which will imitate calorie restriction. Rapamycin is one of them. This is a drug that's actually got a lot of side effects, and in fact it's one that Bryan Johnson has given up because he reckons the side effects are not worth the potential benefits, but it affects one of the pathways that David Sinclair has actually done a lot of the pioneering research on, the TOR pathway, which is influenced by what you eat and actually shapes ageing processes, slows them down, speeds them up in the body.

Tegan Taylor: So, my understanding of the research and from what Luigi Fontana has said is that basically as little as you can eat as possible will make you live long.

Norman Swan: Yeah, and if you go to the animal experiments where they reduce calories by as much as 30%, you do get almost the same increase in lifespan and healthy lifespan in these animals. But remember…

Tegan Taylor: When you say the same, you mean like a 30% increase?

Norman Swan: So a 30% decrease in calories with a 30% increase in lifespan in animal models. It's not proven in humans and it's not proven in real life, because your immune system might be affected, you might be more susceptible to infection, all sorts of things may happen which haven't been fully tested. And of course the whole notion of calorie restriction has all sorts of broader effects on human beings.

Tegan Taylor: Well, are you alluding to…the idea of falling into an eating disorder or disordered eating, they can be deadly.

Norman Swan: Absolutely, they can indeed. And it's interesting that Bryan Johnson reduces by 10% not 30%, so he's not going really radical there. But here's the problem. One of them is one that I've just said, which is he's doing so much you haven't got a clue what's going to work, because he is calorie restricted by 10%, he's doing a lot of exercise, and it's likely that if he gets any benefits, those things alone are probably doing it. But then he's taking all this other stuff. There is a problem, and the problem is two things. One is a word called 'homeostasis', and the other is a word that we've used a lot, and increasingly on What's That Rash?, 'pleiotropy'.

Tegan Taylor: Every time you say 'pleiotropy' I want to play some sort of noise. I've got my Mediterranean diet bell right here, I've got my fine particulate air pollution harmonica here, but I still don't have a xylophone. 

Norman Swan: And the reason for xylophone is that pleiotropy is two things happening at the same time, so you'd be playing a chord on your xylophone.

Tegan Taylor: I still think the harmonica comes pretty close. So the idea of pleiotropy is a gene that has more than one function.

Norman Swan: Or a drug that has more than one function. So it's possible that some of these supplements have what they call antagonistic pleiotropy, or negative pleiotropy. So it works positively on one thing, but while you're not noticing, it's having a negative effect in another area. And homeostasis is this…we survive well because we are well balanced as human beings. And if our blood pressure goes up, there's a system to bring it down, unless you've got pathological high blood pressure. For every action there's a counter action to keep the body in balance. And if you take these supplements, it's likely that what happens is that the body reacts to them. 

So if you take rapamycin and you shift that TOR pathway, the body recognises that as abnormal and opposes it and pushes back. So, in theory, something like rapamycin, or one of the rapamycin derivatives which are safer, should work, and in the laboratory in animals they do seem to extend lifespan, but in humans they don't seem to have that effect because the body pushes back.

And what some people are arguing is that maybe there is something to the supplement idea of slowing down the molecular pathways of ageing, but if you do it at high dose all the time, your body fights back, and while you might get a response initially, eventually you stop getting a response.  What some people think should happen is you get a cocktail of the substances that in theory should work, and you use a cocktail of them, not just one. So, Bryan Johnson, to be fair, is…

Tegan Taylor: I mean, he is certainly taking a cocktail. 

Norman Swan: So that the body is confused about what it's actually having, and you take them in tiny doses so that you don't push the body too hard, so that it learns to oppose it, and you maybe only take it once a fortnight, so that it's like a pulse effect, a low dose that slowly shifts the system. But what Johnson and others are doing is high doses of lots of stuff, lots of different things, and they will interact with each other, the body will react to them, and it just may be counterproductive.

Tegan Taylor: My hiccup with a lot of these sorts of stories is the sort of ethics of a couple of people getting to live longer or forever or whatever, and so there's a little bit of that in the mix for me, but fundamentally how much of this is useful to you or me or someone listening? How much of this do we take on board? I don't think many of us are going to upend our entire lives and follow this sort of regime, nor can we afford to. But if there is anything to take from this movement, what is it?

Norman Swan: I don't think there's much to take from Bryan Johnson, because it's not a randomised trial. He's not even doing a trial…another favourite thing we talk about, N-of-one trial, in other words doing it on himself. He's not doing it in any kind of scientific way really, he's taking a cocktail, it's all a mishmash of stuff. You know, it's not doing one thing at a time. So the likelihood that he's going to find one magical thing that makes a difference is low, is very low, because there's so much going on. And then if it means that you've got to put electric shocks on your penis and not have sex ever again and sleep eight hours and not have a life, nobody's going to do that. 

I think there is a bigger ethical question which we all need to ask and we do ask reasonably frequently in Australia; why do some people live longer and healthier than others? And that is socially and economically determined. So if you get the train in Perth going north or south or west, then the life expectancy of people along that line drops almost by station, not quite, but the further out you get. If you get in the train in Melbourne and you go west or even east actually, the further east you go, once you're beyond the wealthiest suburbs, life expectancy drops. West in Sydney. And then there's the gap, which is shameful in Australia, the nine-to-11-year life expectancy gap between us and Aboriginal people, and that is socially and economically determined. And so you could actually have people living younger longer by changing social and economic and educational policy in this country and other countries to narrow that gap, because it's that gap that causes the bigger gap. It's not healthcare, it's social and economic. So that's the big ethical question here. 

Now, maybe some researchers in some of this area will come across something that is worth doing, but in the end if you eat an unprocessed diet, if you watch your calories so that you're not consuming more calories than you need, and you're having reasonably intense exercise, which is both aerobic and strength based, and you don't smoke, you are going to live younger longer. Question is, will you live younger and longer as much as Bryan Johnson? Well, you might, because who knows what he's taking that might kill him sooner.

Tegan Taylor: Well, his whole mission is Don't Die, Norman, and I'm offering you the chance to do a throw-down; is Bryan Johnson going to never die?

Norman Swan: No. As much as I wish him good luck, he's going to die just like the rest of us. The question is, when and in what shape, and whether he's going to be happy.

Tegan Taylor: Exactly. Well, thank you very much for this trip down longevity lane, Norman, I can't believe we actually got through it as efficiently as we did. 

Norman Swan: Well, you know, you warned me at the beginning. I kept my mouth shut.

Tegan Taylor: I did. Well, if you have a question that you'd like us to answer, or if there's a particular facet of living forever that you would like us to dig into in more detail, the email address is the same, thatrash@abc.net.au.

Norman Swan: See you next week.

Tegan Taylor: See you then.