Medicine 3.0: Extending Human Lifespan with Dr. Peter Attia

Welcome to StarTalk, your place in the universe where science and pop culture collide.

StarTalk begins right now.

This is StarTalk Sports Edition.

I’m your host, Neil deGrasse Tyson, your personal astrophysicist.

Got with me my co-host, Gary, Gary Riley.

How are you, man?

All right.

All right.

When he’s not otherwise announcing soccer, he is with us here on StarTalk.

Former soccer pro.

Always good to have you there, Gary.

And of course, Chuck Nice, Jack.

Hey, former nothing.

Former nothing, okay.

That’s why we have you.

That’s why you got me.

That’s why I’m a building.

Former nothing.

That’s why you always, every time we call you, you’re there.

All right.

For today’s topic, we’re thinking about human longevity.

And is it a good thing?

What does it mean to live to 200 if you have a 200-year-old body, for example?

So we’re going to get to the bottom of that and with the obvious connections to how long can someone be at the top of their game, athletically, just as an example.

And so, Gary, what have you put together for today’s show?

Let’s meet our guest, Dr.

Peter Attia, Stanford University School of Medicine, trained at Johns Hopkins in general surgery for five years.

Founder of Early Medical, a practice that applies Medicine 3.0, which we will be getting into shortly.

Host of the podcast The Drive, author of Outlive, The Science of Longevity, and you’ll love this one, once planned to take a PhD in aerospace engineering.

But he didn’t?

But he didn’t?

Well, ask him.

He may have done it.

The whole show will have to get on his case for not getting the PhD in aerospace engineering.

He may have tucked up his sleeve somewhere and he’s not wearing it.

He’s a veritable Ponce de Leon and you’re talking about aerospace?

Scott’s teaching us to live forever.

Good.

Very good point.

And we all have to remember who Ponce de Leon is.

But yes, he’s a Spanish explorer who went searching for the Fountain of Youth.

And the reason why I know that is because I wrote a book report on him when I was in fifth grade.

And so, if you have it.

Okay.

Well, here you go.

So, Peter, welcome to StarTalk.

Thanks for having me, guys.

So, Peter, is our human body really built?

Or have the capacity to last longer than we are right now?

And I ask that, you know, it’s a really obvious question.

And it’s not clear how obvious the answer will be because I know we are living twice as long as we were 150 years ago or so.

And we’re living longer than, at least in heartbeats, than any other mammals on Earth.

So we’re doing something right.

And you’re thinking we could just keep at this.

Yeah, I mean, I do think there is a limit to human lifespan.

Where we are in relation to that limit, I don’t think anybody knows.

And I certainly don’t think it’s significantly longer than where we are.

In other words, I, you know, when people talk about, oh, we’re all going to live to 200 or kids born today are going to, you know, be effectively immortal.

I just have a very hard time believing that.

And of course, there’s nothing that’s black and white in science.

Wait, wait, wait, Peter, you’re trying to sell a book called Longevity.

Could you say nicer things about living longer?

We want to help you sell the book, Peter.

Yeah, so remember, longevity is two pieces to it.

And you kind of alluded to this at the outset, right?

But one of them is the lifespan piece.

And that’s the easier one for people to think about because it’s binary.

You’re either alive or you’re dead, you’re respiring or you’re not.

But an equally important part of this, if not, I think more important is the health span piece.

And that part’s analog.

And I think that’s the part that is much more subject to the individual’s views on the quality of their own life.

And two people can have a very different set of metrics for what constitutes quality of life there.

I think what’s abundantly clear is that while our length of life has indeed doubled, as you stated, Neil, from about 40 to 80 since 1900, it’s not clear that that has come with a doubling in the quality of life.

So we’ve basically traded one set of problems for another.

We’ve effectively solved the problem for the most part of acute death, largely brought on by infectious diseases and trauma.

And we’ve shifted that over to chronic death, for which we don’t actually have a great solution at this time.

So just to be clear about language here, so acute death would be you’re live one minute and you drop dead the next.

And chronic death is there’s some long disease that puts you in the hospital for some time and then you die.

Is that what you mean by those?

Yeah.

I mean, so when you think of chronic diseases, you think of what I kind of talk about as the four horsemen of disease, the atherosclerotic diseases, so heart disease, stroke, cancer, neurodegenerative disease such as Alzheimer’s and Parkinson’s, and then of course the whole cluster of metabolic diseases around type 2 diabetes such as non-alcoholic fatty liver disease and insulin resistance, etc.

Those things percolate for years and in some cases decades.

And even when someone dies suddenly, for example, a person drops dead of a heart attack, that process was brewing inside their coronary arteries for decades.

You know, but isn’t it true that people didn’t get a chance to experience chronic death as short as maybe 100 years ago?

And that’s because often external forces intervened and affected life.

You’re talking about pandemic, something we just went through.

You’re talking about all kinds of infectious diseases and then also something as simple as breaking a hip or an arm.

You die of an infection, like, you know, crap that we take for granted now killed everybody back in the day.

That’s exactly right.

I think that’s what he just said, Chuck.

But the point is, but to Chuck’s point, it’s not that these are new problems that you cite, these chronic diseases.

It’s that we didn’t live long enough to have them show up.

Well, I would say there’s two things there.

So everything you said is right, Chuck, that we basically didn’t earn the right to die of chronic diseases back then because we didn’t live long enough on average to have them.

However, I think there’s plenty of evidence that our current environment, while remarkable in many ways, right?

Modernity has brought great things.

With it, it’s come at a cost.

And the cost has been we eat too much, we don’t exercise enough, we don’t sleep enough, we’re under too much chronic stress.

And those things, I would argue, are also exacerbating the problem.

So we have this ability to live longer and be more exposed to these things that therefore render us more susceptible to chronic disease.

Doctor, are you suggesting that current medical science has been looking for the answers in the wrong places, like treating symptoms and conditions rather than looking at the early identification and therefore prediction and prevention?

So is this what you’re calling Medicine 3.0, because that’s a new terminology?

No, that’s what I’m calling Medicine 2.0.

Medicine 2.0 was a really successful playbook for treating the problems that were killing us basically for all of human history.

And there are basically two huge things that catapulted us from Medicine 1.0, which was basically kind of witchcraft and voodoo medicine, into Medicine 2.0.

So the first is sort of Francis Bacon coming along in the late 17th century or mid-17th century effectively coming up with a new frame of thinking about science.

So we collectively can sit here on this podcast today and take for granted something called the scientific method, which is that you, I don’t need to state this to you guys, but you make an observation.

You observe something in the natural world, you make an observation, you formulate a hypothesis, you design an experiment to test that hypothesis, you measure the results of the experiment against the prediction of the hypothesis, and you correct.

And we iterate and iterate and iterate.

Well, we, you know, people who are in science today take that for granted.

There was a day that didn’t, that was as foreign to the world as an airplane was.

Right.

So that, call that step one.

Step two was more technical, and it was basically the development of the light microscope.

Those two things, separated by a couple hundred years, effectively allowed us a window into a world that then allowed us to create therapies, namely anti-microbial therapies and vaccines, that allowed us to basically eradicate, for the most part, communicable diseases, infectious diseases.

Not in my child.

Not in my child, doctor.

You keep your vaccines to yourself, okay?

Trying to mind control my kid.

You’re not going to mind control my kid.

I’m telling you right now.

You keep your politics to yourself.

No, no, his vaccines don’t have microchips.

The polio vaccine had no microchips.

I’m sorry, okay, in that case.

So that playbook worked very well.

The problem is the systems that were required for that system to work, for example, the randomized control trial, don’t work very well in treating cancer or preventing cancer or in preventing cardiovascular disease because of many factors that we don’t have to get into now, but among them the chronicity of those diseases in the time course and the complexity of the interventions used to prevent them.

You see, it’s really easy to do a randomized control trial in humans when the intervention is take this pill versus take this placebo.

That works pretty well.

Imagine I said, listen, guys, we’re going to do an experiment where the next 30 years these people need to eat exactly this way, these people need to eat exactly this way, these people need to exercise exactly this way, and then in 30 years let’s see how things are going.

I mean, that experiment can’t be done for so many reasons that it’s not worth going into them, and therefore we’re stuck.

I think you just brought up something that is so important for people to understand, and I think we’re saying it like a throwaway, which is, you know, your RCT, and RCT really revolutionized, that was kind of like a medical revolution, because I think what people forget is that a lot of times, no matter how you get sick, your body sometimes will recover.

A lot of times will recover.

So there was a time where they were just like, eat some dirt, and then you would recover.

And then they’d be like, see, dirt is the answer.

So, I mean, maybe you should…

What does RCT mean?

Randomized control trial.

And I’m glad you brought that up, Chuck, because we are throwing that around without giving it its due course, which is, again, that’s a big part of the scientific method.

Randomization is essential to eliminate bias and to eliminate confounding and to determine causality.

So, causality is such an important thing in science, and without those tools, it’s very difficult to establish causality.

And that’s why Medicine 1.0 was all about bad humors, right?

Elixirs, nonsense.

I know all about bad humor.

Chuck, you’re occasionally good for good humor, I think.

Wait, wait, wait.

So, Peter, so what you’re saying is, in modern times, since those experiments you described are not executable for many reasons, including at some level just the ethics of what it is to force someone in their life to do something that you think might give them cancer, but now you want to see if it actually does.

So we’re left with finding isolated populations in the world that might have those habits just as a matter of their culture, or their religion, or their traditions.

And that should be able to work as well, right?

Well, but not by itself, right?

Because it still can’t establish causality.

So we still have this problem of we have to get away from the gold standard and instead rely on a whole bunch of imperfect things and make inferences based on a lot of imperfect things.

So yes, we would still rely on epidemiology.

Let’s remember something.

The relationship between cigarettes and lung cancer was never established using an RCT.

It was established using epidemiology.

But the epidemiology was so compelling there that we are very confident in establishing causality and making bold claims policy-wise and medically about those things.

We had a huge sample too, you got to remember, because freaking everybody in the world smoked back then.

Well, it’s the sample size was less the issue.

It’s the magnitude of the hazard ratio and the dose response that probably played a greater role.

In other words, it was the ability…

So first of all, the hazard ratio was like 10, right?

This is a log more than the hazard ratios we see with things like, you know, eating this food versus eating that food, where your hazard ratio is like 1.17 or something like that.

And then you had the dose effect.

So the more you smoked, the more likely you were.

So there’s this guy named Austin Bradford Hill, who was kind of the godfather of the statistical methods utilized to establish and understand RCTs.

And he proposed these nine basically checks that you would run through your epidemiologic observations.

And the more of those checks you had, the more confident you could be that causality was, in fact, underneath this correlation.

Cool.

That’s cool.

So, Doctor, the phrase people get sick, right?

Are we saying now that’s the wrong way to look at it?

The person gets sick.

And I need to know that person because it’s that person I’m treating.

So, therefore, I have to really have an intimate knowledge of that person because they might be presenting the same symptoms as the person in the bed next to them, but one’s bacterial, one’s viral.

So, the treatment for both is the same.

One of them is not going to cure.

One’s not going to get better.

So, we need to have, is that what you’re saying?

We need to have that specific knowledge to treat that person.

Yeah, this is the next layer.

This is now how we have to get to medicine 3.0, because what you’ve highlighted is a very important point that also gets lost in the culture of only the RCT is valuable.

Keep in mind, the RCT takes a whole bunch of people who are heterogeneous, and it finds the average outcome.

So, it spits out homogeneous from heterogeneous.

And to your point, at the end of the day, any physician who’s taking care of a human being will tell you that you can have exactly the situation you’re having.

And by the way, I’ll go one step further.

It’s not just, well, these two are both sick, but it turns out one’s viral and one’s bacterial.

It’s like, no, no, no.

These two people are having the exact same heart attack or these two people have the exact same cancer, but there might be different factors about them that will make one susceptible to a treatment while the other is not.

Well, that’s what’s happening right now with genetics and cancer treatment right now, you know.

Well, wait, but all right, but getting back to the theme of this program, you’re, all right, so suppose we do cure all that.

At the end of the day, we live longer because we’re not dying from those disease, but we’re still getting older, right?

And so, is there a limit beyond susceptibility to disease that you think we will still confront?

Is there another wave of things we will hit when we all live to 150?

Oh, my gosh, look what we’re dying of now, all right, because we got to live that long.

Is this in our future?

This is actually a pretty interesting debate within the aging community, because what you’re really asking, and I think it is the jugular question, is do we take it as…

Oh, I love your medical analogy.

That’s a jugular question.

That question just slipped my damn throat.

Okay, I love it.

I love the extra vocabulary here.

Okay, go on.

So, independent of disease, what is aging?

Now, there are these nine hallmarks of aging that obviously play a role in disease.

So, let’s take one of them, for example, genomic instability.

There’s no mystery here that the older we get, the more we accumulate genetic mutations.

Well, that directly feeds into at least one of the four horsemen.

Cancer is fed by that.

In fact, that’s the sin qua non of cancer.

Cancer arises when cells acquire somatic mutations and those mutations produce a phenotype, meaning they produce a cell whose properties are two things.

One, it no longer responds to cell cycle signaling, so it will grow in an unregulated manner, and two, it has the capacity to leave its site of origin.

So, let me, just as a regular person, see if I understood what you just said there, because that was a lot.

There’s nothing regular about you, but please continue.

But did you just say, and if I’m wrong, I’m wrong, I don’t care.

I’m just telling you what I heard.

That cancer basically is already in you, but what happens is you’re making a replica of yourself over the years.

It gets to a point where you’re replicating those cells, but they no longer, they kind of say, I’m going to break the rules.

I don’t care about the rules.

I’m not going to generate or regenerate the way I should.

So, as a matter of fact, forget it.

I’m going to have a party and I’m going to regenerate like crazy.

And, you know, so basically that’s cancer.

Yeah, think about it.

If a person gets colon cancer, like I’ll just pick that because it’s the third leading cause of cancer death, that grows out of colon cells that are in your body.

And those are cells that have to reproduce constantly because you’re constantly sloughing off cells in your colon.

But the problem is if one of those cells acquires a set of mutations that basically makes it deaf to the signals that tell them when to grow and when to stop and acquires mutations that allows it to leave the colon and go somewhere else, all of a sudden it grows and grows and grows.

And everybody around is saying, hey dude, you got to stop, you got to stop, you got to stop.

He’s like, I don’t hear you, I don’t hear you, I’m just going to keep growing.

And oh, by the way, I can leave and go to the liver and take up residence there.

That’s what’s going to kill you.

But let me go back to Neil’s question, right?

So you asked a question, Neil, what if you somehow figure out a way to cure all cancers?

And what if you somehow figure out a way to cure heart disease?

And what if you somehow figure out a way to not get Alzheimer’s disease?

Will we still age?

And I think the answer is yes, right?

I still think there are enough of these other processes that are going on where, for example, our mitochondria, which are the little energy producing organelles of our cells, become less and less effective.

And that will, for example, mean you are weaker, you have less energy, even absent a quote-unquote disease.

So I don’t know, truthfully, which side of this debate I come down on, right?

Is aging necessarily an implication of disease, or is there an aged phenotype absent disease?

I probably lean more towards that side of the philosophical debate, though.

Now you just made me think of this.

What happens, they say, whatever doesn’t kill you makes you stronger.

Is it possible that it’s just the opposite, that you get a disease, that disease makes you weaker, and then later on in life, you’re actually weaker because it just weakens you, and now something else has come to attack you, and that makes you…

I mean, I think there are examples of both, right?

So the process you’re describing in the first part of that statement is what we call hormesis, right?

What doesn’t kill you makes you stronger.

So again, to bring it back to your favorite subject of vaccination, vaccination is a form of hormesis.

We introduce a small amount of the virus.

Sometimes we would disable it or whatever in the traditional sense.

Let’s ignore the mRNA vaccine.

So we would give you kind of a deactivated or weakened virus or attenuated in some way.

It makes you a little sick, right?

But your body rises to that occasion.

It develops a huge memory response to it.

And the next time that virus shows up, you’re ready to pounce it.

Exercise is probably my favorite form of hormesis.

In the short term, exercise does everything wrong to your body.

It raises your heart rate, it raises your blood pressure, it lowers your heart rate variability, it induces stress hormones.

Everything about exercise while you’re exercising is unhealthy.

It damages your muscles, right?

Sure.

Yeah, it tears down muscle fibers.

So if you’re exercising for two hours a day, that two hours isn’t what’s making you healthy.

What’s making you healthy is the other 22 hours of the day when your body responds to that, adapts to that, and gets stronger as a result of that.

Poor mises.

We got to take a quick break.

When we come back, we’re going to see what role sleep plays in our health and longevity, and what else we might have control over to live the life we hope we want to lead as we get older on StarTalk.

We’re back, StarTalk, with Dr.

Peter Attia, who is an expert on aging and longevity, a medical doctor, and he’s written a book.

And Peter, tell us the title of that book, the full title.

Outlive, The Science & Art of Longevity.

I love it, I love it.

And of course, you’re the host of the popular podcast, The Drive.

And so, let me just lead off, something, a point I wanted to make earlier.

There are people who don’t fully embrace or understand the statistics of disease.

So for example, if the press reports cancer rates are up relative to 50 years ago, how often is it that they’re up because people are simply living longer and then have that susceptibility for having lived longer?

So therefore, they shouldn’t start wondering what’s happening in their environment that could be giving them cancer.

Yeah, it really comes down to how those things are reported.

So as you know, there’s one way to think about this is through the lens of incidence and another way is through the lens of prevalence.

So, and then on top of that, so I think a better example, Neil, might actually be Alzheimer’s disease because that’s the most clearly associated with aging.

So we would say that today, both the incidence and prevalence of Alzheimer’s disease is significantly higher than it was say 50 years ago.

And now the question becomes, what are the confounders there?

Well, one really big confounder is not just that we’re living a bit longer now, it’s that we are much better in our diagnostic acumen.

So what would have been Alzheimer’s disease 50 years ago was mom’s a little loopy and it’s sort of, she’s a bit senile.

Whereas now we have diagnostic tools to make that distinction more clearly.

That said, in every treatment that I’ve looked at, especially with respect to Alzheimer’s disease, the incidence is indeed increasing even when adjusted for age.

So it does suggest that we are actually getting a little less healthy, but because medicine is also getting better, we’re kind of stretching out extra years of life, albeit at probably a lower quality.

So our lifespan, and to put it in the speak of what we discussed in the last segment, our lifespan is incrementally getting longer while our health span is eroding, at least by my definition.

Now, some people have a different definition of health span that is more, frankly, I think, not strenuous enough, which says it’s the time of life you are free from disability and disease.

I think that’s a pretty useless definition, truthfully.

I think we want to be more particular about cognitive and physical capacity.

Dr.

we’re going to jump into the neurodegenerative process and diseases because you cite that as one of the four horsemen of disease in your book.

Wait, wait, wait.

We left off right at the end of the second segment where you talk about exercise being the best thing.

So, if I do my ab crunches or whatever, you know, and or my planks and I pump some iron and I, you know, run the track, I still don’t live to 150.

No.

So, what’s up with that?

But it doesn’t make a difference because I look amazing.

Are you happy now?

You feel better for that?

Yes.

You look good on the beach.

Yes, okay.

But exercise, I would argue, makes a bigger difference than any other intervention we have.

So, you have these interventions like whether it be, you know, the right nutrition, exercise, sleep, etc.

But the data would suggest that exercise has a bigger impact on your longevity than anything else.

And the, you know, the two metrics that we have that are probably most rigorous to measure that is strength and cardio respiratory fitness, peak cardio respiratory fitness, or something measured by VO2 max.

Gary, you must have had a VO2 max back, the test done back in the day.

We chiseled that on the side of the cave back in my day.

It was just pretty historic.

Well, look, it’s a test anybody could go and do, right?

So, you all could go do this next week.

So, the thing is, doctor, I mean, as much as I do know, we have these, and you mentioned these guys before in the, in segment one, the mitochondria, because there are little powerhouses, as far as I can see in my layman’s terminology, but do they not diminish in terms of number and efficiency as we get older?

And exercising, as you just, Neil just pointed out, you know, do my abs, pump my iron, run the track, but that doesn’t help as much.

So, there has to be a way to exercise for efficiency.

Well, it does, though.

Exercise does indeed improve mitochondrial efficiency, but it has to be the right kind of exercise.

So, for example, if that’s your specific aim, you have to do it correctly.

So, a silly example would be, if you tell me your objective is to have bigger biceps, it doesn’t really matter if you do all the leg extensions in the world.

And similarly, if you’re telling me, as you should be, that you want to target mitochondrial efficiency, and I would argue we should, then you have to train in a way that targets that.

And the way to do that is a type of training called Zone 2 training.

So, Zone 2 training is aerobic steady state activity that is right at the threshold of lactate production at the mitochondria.

Now, for people who don’t want to do what I like to do, which is actually measure lactate production while exercising, a very simple heuristic for doing this is assessing your perceived exertion during exercise and making sure you’re at the following threshold.

You are able to speak, but you don’t want to.

Wait, wait, wait.

Let’s get the vocabulary.

So, we have lactose, which is sort of…

No, lactate.

No, lactate and…

Yeah, yeah, they’re totally different.

Lactate and acid.

Look, please, so let’s help Chuck out here.

Let’s help out Chuck.

And when I think of the lactate acid buildup in muscles that can work back against you if you reach that zone, and lactose, which is a milk churn.

Right.

So go ahead.

So lactate is a byproduct of anaerobic metabolism, which is just another way of saying when your muscles are demanding energy at a rate that can’t be met purely through the much more efficient, but slow burning process of utilizing oxygen, what’s called aerobic metabolism, you turn to this other method, which has the benefit of giving you ATP or energy very quickly, but with a nasty side effect, which is it’s also starting to accumulate lactate and if you can’t tolerate that lactate buildup, which most of us can’t at a high enough level, your exercise becomes limited.

Now what you want to do is increase the capacity of your mitochondria to develop ATP, to produce ATP at the highest work capacity possible.

And to do that you have to train right at that threshold.

And as I said, you can do this in a very technical way, but you can get 80% of the value just by saying, look, I’m going to go walk on a steep incline on the treadmill and I’m going to titrate that incline and speed until I’m right at the point where if my wife comes in and talks to me, I can talk with her a little, but I just don’t want to.

If you can’t talk at all, you’re beyond that.

You’re actually into too much lactate production and you’re not going to get that training adaptation.

And if you’re too far below that, if it’s actually easy to have a discussion, then you’re not training hard enough.

So that’s a very specific example where you use exercise in a very targeted way to train a very specific adaptation.

So what is it then that there’s so much around this hit training, this high intensity training, so that it’s kind of like what you say, except you do exceed the threshold, but only for short bursts, and then rest, recover, do it again.

What’s the difference there?

Significant difference.

There’s nothing wrong with hit training, but it really comes out of a sort of human condition of looking for the minimum effective dose for everything.

So if someone says, look, I’ve only got 30 minutes a week that I’m willing to exercise, how can I make the best use of it?

Then yeah, you’re probably, if you’re truly going to draw that line in the sand and say, I’m only willing to do 30 minutes a week, yeah, you’re probably better off doing 10, you know, minute short bursts of brutal activity three times a week.

What I’m saying is, let’s put that caveat or constraint rather aside and say, what’s actually the best thing to be doing?

And the data would suggest probably at least three, if not four hours a week of just that kind of steady state cardio.

And then we have to talk about the strength training and some of the higher intensity stuff as well.

And before you all say who the hell has time for that, I would argue if you’re in the business of trying to live longer and live as well as possible, you have to ask yourself the question, what’s more important?

So, doctor, when your patients come to you and you explain the zone two exercise and the benefits they’re in, why do you advise them to do the VO2 max training as well?

What is the synergy between the two of them that’s so effective?

And tell us what VO2 max is.

Sure, sure.

So, VO2 max is this test that measures literally the maximum amount of oxygen your muscles can utilize.

And to do that, you’re strapped up to this mask and you’re put into a very stressful situation, usually on a bike or a treadmill, and you are pushed until you fail.

And during that period of time, these sensors, so there’s an O2 sensor and a CO2 sensor on the mask, it will basically tell you this is the maximum amount of oxygen you were able to consume in liters per minute.

So it’s calculating something known as the ventilatory rate of oxygen consumption.

And the bigger that number…

That’s what the V stands for, ventilatory?

Yeah, the V is ventilatory, right?

So VO2 max is ventilatory rate of oxygen consumption.

So it’s technically VO2, it’s VO2 max.

And so the bigger that number, the fitter you are and the longer you live.

In fact, there is no metric we have that is more correlated with lifespan than VO2 max.

So, Dr.

if I don’t live in a $50 million penthouse apartment and have a Peloton and have an elevator…

Have you seen the share price of Peloton?

I don’t think you need to live in that apartment anymore to have a Peloton.

Wait, is there stock down?

Thanks for the tip.

Yeah, exactly.

What are we missing?

Chuck, let’s get busy.

So, the thing is, I got a bad knee, my hip plays me up.

Stuff’s not easy for me to do.

This is why I don’t live on the penthouse, because the elevator gets broken and I can’t walk all those flights of stairs.

So, what are we trying to do?

Because, you know what?

Life takes a bite out of us.

It doesn’t allow us to be as perfectly fit as we once were or we’d like to be.

So, how are people working around these sort of impediments to get to where they need to be?

Plus, I want to hear more about sleep too in this segment.

So, make sure that falls in here somehow.

So, look, I think one has to come up with ways to get the circulatory system moving.

So, if a person says, look, I can’t walk on a treadmill or I can’t climb stairs, then maybe they can get on a bike where there’s less impact.

Or if that doesn’t work, maybe they can be in a pool or on a rowing machine.

But unfortunately, this type of activity has to be done.

And if injuries are preventing all of that, then those injuries have to be addressed.

You know, that is an important part of living longer, is being free of pain.

That factors in very heavily to my definition of health span, at least, where freedom from pain is a pursuit.

And most people do not follow up on injury.

Most of us have received some type of injury in life, and then they don’t follow up on the rehab for that injury properly.

And then I just recently found out that no injury heals.

It just stops hurting until you’re 49 years old.

It did not heal.

It just stopped hurting.

And then all of a sudden one day you’re like, why is this hurting again?

And yeah, it’s because you didn’t do the rehab, you big dummy.

So Chuck is writing a book, all the shit that happens to you when you turn 50.

It’ll be out next year, people.

Alright, so, I used to have one coach who would say, the harder you work, the harder you have to rest.

And for years no one gave a damn, right?

But now you have got athletes wandering around with the wrist ornaments that will tell their medical team how much sleep they got, the quality of sleep they had.

Now, if it’s good enough for elite athletes, it’s surely doing something special.

So what is the whole secret behind getting sleep?

Because we’ve kind of ignored it for most of our lives.

Yeah, no one even thought about it, yeah.

Yeah, and look, I did till about 10 years ago.

I was very much of the mindset that I’ll sleep when I’m dead.

But I think the science is pretty unequivocal here.

And so, too, if you just…

Once in a while it’s nice when evolution makes such an obvious statement, which is why did evolution not get rid of this thing that kept us unconscious a third of our lives, unable to hunt for food, reproduce, fend ourselves against danger?

So there’s a pretty compelling case for why we and every other species on this planet require sleep.

That’s a great point.

And I’ve joked about this where aliens come to Earth and say, what, these humans are semi-comatose for one third of the rotation of their planet?

Like, what’s up with that?

They would be completely stupefied by it.

And we take it all for granted, right?

So tell me, what’s it doing for us?

It turns out it’s doing a lot, right?

So it’s not just restoring things in your brain.

So one of the most important functions of sleep is basically cleaning up debris through what’s called the glymphatic system.

So Matthew Walker uses this analogy of picture your brain as Manhattan where the streets represent the area between cells and at night the street sweepers are coming out and getting the trash out of those areas.

It’s also a time when you consolidate memory, right?

You can’t consolidate memory or new skill absent sleep.

It’s also a time when some of the most important hormones in your body are being synthesized or at least the signals that tell those hormones to be made.

So, for example, testosterone, while it’s not made in the brain, is made in response to something called follicular stimulating hormone or follicle stimulating hormone and luteinizing hormone.

Those are maximally produced at night as is growth hormone and things like that.

But it also regulates very important things, which is easier.

And sometimes there’s things we don’t fully understand how it’s doing it, but we can see experimentally when you, even for a short term, deprive sleep, you can induce a horrible physiologic state.

And the most obvious example to me is that of insulin resistance.

This is the precursor to type 2 diabetes.

Just a week of significant sleep deprivation, taking normal healthy people and restricting them down to four and a half hours per night will induce a state of profound insulin resistance in about a week.

So you get the sense, even without fully understanding mechanistically how this is happening, that disruptions of sleep lead to horrible consequences both above and below the neck.

So with shift workers, with shift workers who work those awfully unsocial hours, there must be a phenomenal risk of having all sorts of problems.

Unless they sleep during the day.

I mean, they can still sleep during the day.

You’re not, your body’s programmed to do it at a certain time of the day and all of a sudden you’re turning that on its head.

Can you, well the question is, the question is, can you change your circadian rhythm?

Is that possible?

You can, but it requires a lot of manipulation of light.

So one of the, there’s three basic driving forces for sleep.

One is cortisol, one is light, and one is adenosine.

So we could talk about all of them, but let’s just talk about the light one.

The light one is sensed through something called the pineal gland right behind the eyes.

And so all that gland is basically trying to ascertain is when is it getting dark enough that I can start secreting melatonin, which is a pro-sleep hormone.

So one of the challenges that a shift worker is going to have if they’re not paying attention to it is how do I make sure when I sleep I create enough of a darkness environment that I get that hormone to be produced to shift my physiologic state.

And by the way, that means that they need light when they’re working.

And it has to be kind of the right kind of light.

And unfortunately, there’s no perfect substitute for sunlight.

Well, and once again, Dr.

I know you went to med school and everything, but the penile gland is much lower in the body.

Chuck has his own medical school.

Chuck Nice School of Medicine.

And it exists below the waistline as well.

We’re going to take a quick break, but when we return for our third and final segment, we’re going to get deeper into sort of our neurological health, emotional health, other dimensions of what we will care about as we get older.

We’re back on StarTalk Sports Edition, completely devoted to longevity.

And we’ve got in-house, as our expert, Dr.

Peter Attia.

And he is host of the podcast, The Drive.

And he’s got a book out.

And again, tell us about your book, Peter.

It’s called Outlive!

The Science & Art of Longevity.

Yeah, I love that title.

So Gary, keep us going here.

What’s next up?

What have you teed up?

All right, so we kind of touched on in Segment 1, the Four Horsemen of Disease.

You know, all these things that fight us in our aging battle.

So I thought maybe we’d try and saddle one up and ride it a little bit harder and find out a bit more.

And that would be neurodegenerative disease.

Because I think as we get older, a lot of people’s biggest fear is, you know what?

Is my head going to be really good?

Or am I going to lose the plot?

What’s going on?

So there has to be a way, because once you get to that Alzheimer’s, and I sadly lost my father to dementia, once it gets to a certain point, this trend only goes in one direction.

But is there a way in the future we can successfully battle something like this?

Or prevent it, yeah.

Well, I think that’s again the important distinction.

And I’ll be honest with you, I’m far more optimistic in our capacity to prevent, or at a minimum, significantly delay the onset of Alzheimer’s disease than I am in our capacity to treat it once it takes hold.

And part of the problem is just that protein folding is a really common problem.

So the easiest example, and admittedly this is an oversimplification, is why does an egg change color when you cook it?

Like, why does the white part of the egg?

I think that’s one of the most fascinating things in the kitchen.

Between you and me, I just say, here’s a transparent fluid, and it bada-bing turns white and exposed to heat.

It’s like we should marvel at that more often than we do.

And so here’s the equally remarkable thing, Neil, which is why can we never go back from white to clear?

So basically, like, there’s a real problem with folding and unfolding proteins.

And once you move in that direction where…

So the main protein, of course, like, you have albumin and things like that inside the egg protein.

Once you apply heat, you’re basically changing the shape of the protein, and it fails to be translucent anymore.

And something very similar is kind of happening in the brain, right?

Which is, as the amyloid beta plaques and the neurofibrillary tangles are wreaking havoc in the neurons, it does not appear to be reversible any more than it appears reversible to take a white egg and return it back to a clear egg.

So, I think that if we’re going to see successful pharmacotherapy, it’s going to have to be applied very early.

And that’s why I think today what’s exciting is the development of biomarkers that are being applied to high-risk individuals before they have symptoms, but identifying the seeds of problems.

So, let’s use an analogy in cardiovascular disease.

I don’t want to wait until you’re having chest pain or God forbid a heart attack to interfere with drugs that lower cholesterol.

Instead, what I’d rather do is say, look, I can measure your cholesterol and I know it’s high and I know what that’s going to do.

And if I really need to convince myself, I could look at a CT scan of your coronary arteries and realize that, oh, by the way, you’re already accumulating soft plaque.

So similarly…

So how do you know if someone is susceptible to Alzheimer’s if they don’t yet have symptoms?

I think the two most important ways are family history.

So that’s a big predictor.

And then the second…

So genetics.

Yeah, and then the second is genetics.

Oh, I’m screwed.

So there’s a gene…

Oh, it’s the same thing.

That’s the same thing.

Family history is…

Not necessarily, not necessarily, because there are many people who get this that are not getting it through the gene that we are most commonly measuring.

So the gene I’m referring to is called APOE.

So apolipoprotein E is the gene.

And this is an unusual gene in that it has three isoforms.

So most genes just exist in one form.

So for example, the LPA gene or the APOB gene, there’s just one, we all have the same one.

The APOE gene used to only exist in an isoform called E4.

That was the one that we historically had for thousands of years.

And about 200,000 years ago, another one showed up called the APOE3 isoform.

And then about 25,000 years ago, the APOE2 one showed up.

What were the cavemen doing to make this happen?

Whatever they were doing, they were like, we got to forget this mess.

Well, it’s interesting.

Here’s a great example of going back to what we talked about earlier, right?

The APOE4 gene, which was the one that our ancestors had forever is the high-risk Alzheimer’s gene.

Ah, okay.

But it served a very important purpose, which is it probably helped us against infectious diseases.

So it was probably a very good gene to have when you were young, especially for most of human history, when you were much more likely to die from infectious diseases.

But it turns out to not be as good a gene to have when you’re old.

Given that you don’t need help with your genes to fight infectious diseases anymore, we have so many other technologies.

What we need is help not getting Alzheimer’s disease.

So 25…

It’s like sickle cell and malaria.

That’s exactly right.

The sickle cell will kill you, but it keeps you alive long enough to not get malaria.

And so these interesting biological trade-offs in our life expectancy, historically…

And it’s a little bit different, right?

Because sickle cell is, if you have to have two copies of the gene to have the phenotype, and that would be negative under any circumstance.

It’s if you have one copy of the gene…

There it is.

That you’re protected from malaria and you don’t have the phenotype.

And that probably explains why that trait has stuck around forever, as opposed to a disease that kills people young.

When you say two copies, just for clarification, you mean that both people have to pass the same gene at the same time to the recipient?

Is that what you mean?

That’s in the case of sickle cell.

You get one from each parent.

Going back to Alzheimer’s, one thing to keep in mind is the ApoE4 gene is quite different in the sense that there’s no evolutionary pressure to get rid of that gene because it doesn’t interfere with reproductive fitness at all.

Right.

So this gene is here to stay, you know, absent like, you know, sci-fi, crisper stuff where we just get rid of it.

But the point is people who have that gene, depending on if they have one or two copies, are at an increased risk for Alzheimer’s disease.

So if you have one copy of the ApoE4 gene and one copy of either two or three, your risk is about two-fold higher.

Maybe as high as three.

Doctor, we’ve exercised our bodies, right, for the aim of longevity.

Now, if someone and their blood work presents with markers that you think might be predisposed towards dementia, Alzheimer’s, do we then not engage in some sort of cognitive skill exercise that is working for our minds as much as we do to exercise correctly for our bodies?

So is the brain a muscle in this regard?

Yeah.

Not exactly the same, but there is an analogy.

But first of all, exercise is still the most important intervention we have for brain health as well.

So that shouldn’t be forgotten.

So the exercise you’re doing for your body is also for your brain, both in terms of reducing inflammation, increasing growth factors such as brain-derived neurotropic factor, BDNF, increasing cardiovascular fitness, which in turn increases vascular fitness.

Remember, a lot of dementia is exacerbated by microvascular disease, anything that deprives.

So just take a step back.

The brain is like 2% of your body weight and 25% of your metabolic demand.

So just kind of reflect on that for a moment.

So anything that compromises any bit of its metabolic fitness is disastrous.

And that’s why small vessel disease, type 2 diabetes, anything that compromises that aspect of the brain is devastating with respect to dementia.

And so exercise helps out.

To translate your phrase, it’s 25% of our metabolic demand.

What you mean is, of all your calorie intake, your body is using one-fourth of it.

Your brain is taking one-fourth of it and the rest goes to the rest of your body.

That’s right.

And despite it only weighing 2%.

Some of our brains are doing that.

Despite it being only 2% of your body weight.

Yeah, I know some people that is, their brain is 2% of their body weight and it’s probably only doing about 2% of the metabolic.

So, to your question, Gary, then, let’s talk about where brain games fit into this, right?

So, the available evidence suggests that…

Brain games are commercial for Chuck, who hosts brain games on the road.

It was two of those when he said, let’s figure out where brain games fit in.

I’ll tell you where it fits in.

You can watch it on Nat Geo, the card on Disney+.

Where Chuck Nice is the host.

Chuck Nice is the host.

Brain games on the road.

There’s an unanticipated commercial for Chuck.

Continue, Peter.

So, it turns out that cognitive reserve is just as important to the brain as physical reserve is to the body, and what we call movement reserve.

So, if you take ten people and you line them up in the order of their physical or movement capacity.

So, you got one person who just kind of sits down all day and does nothing, and at the other end of the spectrum, you’ve got the most sophisticated ballroom dancer of all time who can spin and flip and do all sorts of things.

You can basically assume that they’re going to have that relationship towards their ability to mitigate movement disorders such as Parkinson’s disease.

In other words, the more movement reserve you have, the longer you can tolerate the insult of the neurodegeneration before you start showing symptoms.

The same is true with dementia.

The higher your cognitive reserve, the longer you go before you will experience symptoms.

The question is what type of brain activities boost cognitive reserve.

I think contrary to what people had hoped, it’s not playing Sudoka or playing crossword puzzles or things like that.

Those things are very narrow in what they are doing for your brain and they tend to just make you better at those things.

Whereas doing something very complicated, doing much more cognitively complicated tasks, like learning a new language or learning a new language, guitar or something like that.

Exactly.

Doing things that have many more moving pieces and requires much more of the brain, those do tend to boost cognitive reserve and therefore give us some protection against cognitive decline.

How about learning a musical instrument?

I think it seems that that’s probably in the take, but once you get pretty good, it’s easier, I think, for people to kind of tone down the learning.

So a lot of it also has to do with how deliberate a person is and how much the thing about it.

So one of my hobbies is driving a race car.

And for me, that’s cognitively insanely challenging.

Okay.

Yeah.

It would have to be.

Yeah.

All right, Doc.

So if we heli…

Because you are so close to this.

It’s right there in front of your face.

So if we helicopter out, do we find all of these things are somehow interconnected and dependent, interdependent on each other for a success in terms of…

It’s okay for me.

My body’s good.

I’m 20 years younger than my actual cell by date.

But my brain’s not there, so I need to do…

And is it all connected or do they just sit separately?

If you’re referring to the interventions that we do, whether it be exercise, sleep, stress management, I think they are all connected.

And I’ll give you an example, right?

If you’re doing everything wonderfully, if you’re following, like, say, Peter Attia’s prescription on exercise, but you’re sleeping four hours a night and you’re checking your email all night and living on social media, getting bothered by it, yeah, it’s actually going to impair your capacity to reap the benefits of that domain.

So it’s better to be kind of a 7 out of 10 on everything than a 10 out of 10 on one of them and a 0 out of 10 on another.

Interesting, interesting.

Well-balanced life, well-balanced diet, well-balanced everything.

I’m a fan of moderation, but only in moderation.

Me too.

Personally.

My swim team had T-shirts made for me one day that said moderation is the only thing worth doing in moderation.

Yeah.

Alright, the one…

Okay, Doctor, the one thing we haven’t really touched on is nutrition.

I’ll call it nutrition.

And then you have a phrase, nutritional biochemistry, which doesn’t seem to be as much fun as me saying eating and enjoying.

So, what are we saying here?

And I’d like to slip in there, just Peter, to get your fast reaction.

Almost everyone I’ve ever met who said they became a vegetarian and never felt better, in their changeover to become vegetarian, it included the onset of an exercise regimen.

And I’m intrigued by this because I, along with you, only you know it from experiments, I know it just from my own life, that I’ve never felt better than when I exercise, no matter what I eat, no matter how much I…

The eating is secondary tertiary to the value that the exercise brings to my body.

So how many people are misunderstanding what are the forces driving on how they feel with exercise relative to their diet?

Yeah, you’ve hit the nail on the head, Neil.

Most of the nutrition research is so heavily flawed in its epidemiology by these healthy user biases.

And so you’re right.

So there’s virtually no epidemiologic study that wouldn’t suggest that vegetarians are healthier than meat-eating people.

However, these studies are simply incapable of correcting for the fact that people who select a vegetarian diet make many other changes.

First of all, you’re selecting just a different group of people.

There’s no randomization to make that happen, but you’re selecting people who are then saying, I’m so health-conscious that I’m willing to give up this thing.

It’s not easy to give up, right?

It’s so ubiquitous.

And in exchange, or as a result of that rather, I’m going to do a lot of things that are healthy.

I’m going to be more mindful of my exercise and my stress.

Yes, exactly.

It’s a life shift, yeah.

So that’s absolutely correct.

And by the way, that comes back to Gary’s point.

Why do I want to talk about nutritional biochemistry?

Because I never want to talk about diets.

I can’t stand talking about diets.

It makes me sick.

And all I want to do is just talk about amino acids, fatty acids, carbohydrates.

How do these things work?

What does energy balance mean?

Yeah, but once you put that all together, you end up with a diet.

Yeah, except I think it doesn’t need to…

I mean, the problem with diets is it becomes…

So, look, food is already an emotional topic for everyone.

It’s probably one of the reasons why I think these diets become so tribal.

I see what you’re saying.

It’s a part of how we identify.

I get what you’re saying.

Yeah, so instead I just want to say, look…

Yeah, you become in-group output.

Right.

Yeah, because really a diet is whatever you’re putting in your body, that is your diet, period, you know?

So, I see what you’re saying is once you divorce yourself from, you know, the emotion, from the social aspect of the diet, from what Neil just said, the in-group, out-group crap, once you break it down to just what…

Now you can talk about it in such a way where it is truly just nutrition.

That’s right.

At the end of the day, you’re eating protein, carbohydrates and fat.

That’s right.

And alcohol.

Alcohol is the fourth macronutrient, right?

So, those are your four things.

And I’m not suggesting you consume much from that group, but we need to acknowledge that there are some people who are getting 25% of their calories from alcohol.

You, my friend, are my favorite doctor ever.

On that happy note, we actually have to…

We’ve run out of time.

Quickly, Peter, what we will do is go out and buy Peter’s book, Outlive!

The Science of Longevity, where we will learn how to tackle and navigate all of the bad hands that adult us and for what it is to be human and to get older.

Peter, it’s been a delight to have you on this show.

Thank you for having me, gentlemen.

All right.

And Chuck and Gary, always good to have you there as my co-host.

Thank you.

All right.

Neil deGrasse Tyson here, your personal astrophysicist, as always, bidding you to keep looking.