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Lifespan with Dr. David Sinclair
Exercise, Heat, Cold & Other Stressors for Longevity | Episode 3
Exercise, Heat, Cold & Other Stressors for Longevity | Episode 3

Exercise, Heat, Cold & Other Stressors for Longevity | Episode 3

Lifespan with Dr. David SinclairGo to Podcast Page

David Sinclair, Matthew LaPlante
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38 Clips
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Jan 19, 2022
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Episode Transcript
0:00
Welcome to the Life Span podcast where we discuss the science of aging and how to be healthier at any stage of life.
0:09
I'm David Sinclair. I'm a professor of genetics at Harvard Medical School and co-director of the pole. If Glenn Center for biology of Aging research. I'm joined by my lovely co-author and co-host. Matthew Laplante, welcome mat. I love that. You called me, lovely. I think you are a
0:27
lovely. You're nice. You're nice. You can be nice sometimes. Hey, today, in our episode. We're going to be talking about exercise and other what you call adversity memetics, but before we get to that,
0:39
Today. Right after we stopped taping in the last episode, you went. Oh my God, iron. And then we had a really great conversation about iron. And so I wanted to bring us back there before we could move forward today. Is that? All right,
0:52
that'd be great. I so the Lost episode, if anybody missed, it was about the foods that we can eat, or not eat, or not eat right live a long time and it was remiss of me not to bring up a pernicious. Element called iron pernicious. Yeah. It's
1:10
it's one of the elements that is turning out to be quite a dangerous element to having too much of in your body increasingly. We see that people have high levels of iron, have accelerated
1:21
aging. Okay? Yeah, but but iron is essential, right? We all need iron. In fact, people supplement with iron a lot of
1:28
times, right? Well, we need our and it's a major component of hemoglobin which carries oxygen which we need, but the levels, don't need to be as high as we once thought. In fact people who live,
1:40
A long time and have these diets that are recommended. I typically see they have lower levels of iron and low lower levels of hemoglobin. And this is not necessarily A Bad Thing.
1:51
Conversely people who have very high levels, either genetically hemochromatosis, or take a supplement and end up with high levels of iron might be predisposing themselves to accelerated aging.
2:02
Okay. So, what about just I've been this plays into your idea about why people should limit their meat intake though, because meat intake meat is high in iron, but red meats, especially are
2:13
higher. Now, that's one aspect, but typically, if people are taking a multivitamin with high levels of iron, this could be a really bad thing, it will accumulate in tissue.
2:21
And we know now that particularly ferrous iron leads to the production of free radicals that damage tissues in the body and even worse. It leads to the accumulation of these zombie Souls, which we call senescent cells. And those Drive the aging process in part large part because they leech see these inflammatory molecules. They cause other cells in the vicinity to become inflamed to age to senescent, even cause cancer.
2:46
Let's let's back up for a second here because I think we're going to talk more about senescence.
2:51
Cells in a coming episode but we have mentioned free radicals before and I think that's a word that gets thrown around a lot and maybe not everybody understands free radical,
3:01
right. And we're not just talking about people in Portland, Oregon
3:04
or Eugene OR
3:06
Berkeley. Yeah. So these are free radicals that these have been around for millions of years, of course, and we've known about them for at least the last 70. These are, there are three main types of free radicals. There's the superoxide.
3:21
Up molecule, which is quite damaging. It can lead to water cold Advanced glycation end products, which are basically proteins that are damaged. It's one of the reasons you want to fast. Sometimes during the day to get rid of these damaged proteins. There's a superoxide anion. It's called which creates most of the oxidative stress in the body. And then there's a third one, hydrogen peroxide, which you can buy a bottle of, and dye your hair blond or orange as my hair went during the Pandemic. Those three things are really bad.
3:51
Dagger here during the
3:51
pandemic. I got bored died. It. How did it look? Horrible. It really went orange. I've been dying at ever since just to cover it up, but it's almost gone. Thank goodness. But this is, this is where Ian comes in. When you have a super oxide molecule. It'll be turned into peroxide by an enzyme called superoxide dismutase, which is extremely important to get rid of that super oxide, which is going to damage the cell. But then you get hydrogen peroxide and we know how bad that is. Look at my hair.
4:21
It, you don't want that circulating. So then what happens is, there's a molecule called glutathione which will turn that into water. But if you have too much iron around there, won't be enough chance to detoxify it, and it will be turned into this hydroxyl radical. And that's a really damaging molecule that goes on to damage your DNA. Your own a lipids proteins and drive, aging and senescence. So you want to have iron enough not to be lethargic to have enough oxygen transported but not
4:51
Super high levels that will cause accelerated
4:53
aging and this is going to be different for different people. Ten percent of the population in the United States has the hfe gene which makes them more susceptible to hemochromatosis, which means they have to be even more concerned. You can't know this without knowing if you carry this Gene though, right? I mean,
5:11
right you need to need to measure things and that's why I myself and I recommend people measure their blood by chemistry and determine whether their iron whether it's free.
5:21
Iron, which is the worst type or even the bound iron are out of whack and you can correct for that. In the case of a normal person. I would say, don't take a an iron supplement Sara Lee though, women may need it certain times of the month, but people who have hemochromatosis there, particularly susceptible to aging and the recommendation typically of a doctor is donate blood if you can.
5:42
Okay, so just to like, go over, what we talked about last time, really quickly, you advocate for a plant.
5:51
Based diet you advocate for low iron levels. What am I
5:56
missing? Well, we're going to talk about that today. What type of exercise works best.
6:01
I was just talking about how we should eat. But yeah,
6:04
well we let eat less often either. That's awesome. Yeah. So what I've gone from not eating breakfast now to not even lunch as well and just focus on dinner and giving my body a rest from food overnight and through the middle of the day so that it turns on our defensive jeans against aging. Those three
6:21
It's the mtor, which senses amino acids or lack thereof, the am PK which sensors energy, which is glucose, mainly and the sirtuins which I work on that sense. All of those things including exercise and those three protective mechanisms. We can turn on by eating the right things, eating less often and
6:39
exercising and this leads in really well actually to what we're talking about today because what we're talking about is bringing your body into a state of perceived adversity, as a way to turn on these jeans.
6:51
Before we can do that.
6:53
We got some business to take care of,
6:55
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7:22
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8:23
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8:53
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9:22
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9:32
checkout. Oh, so let's get into this. Um, in this episode we're talking about some of the things that people can do to create and mimic in their lives. The biological adversity. That's more conducive to better life spans on health plans that we
9:50
call these adversity
9:52
memetics.
9:52
Call these that I mean like when you say we call these at is like you and I call them that because I know we call them that but is it like is that a turn that scientists use? Did people actually use right? We just made it up. You're just making it up, but it's a good work. Right? We'll use it try again. So. So and the reason why adversity is important ties, back to this idea that you've proposed of a survival circuit. So before we move forward in this, let's talk about the survival circuit. We don't have to go way way back in history,
10:20
not full. Billy news will come forward.
10:22
In time a little bit. Yeah,
10:23
you can't you can go back four billion years and that's in the book. But we're going to start in the 1990s with Cynthia Kenyon and her work on C. Elegans.
10:33
That's a good starting point. So, in the 1980s, it was all about just free radicals. We didn't know that aging could actually be controlled by any genes. Certainly not single genes. And Cynthia came along as a young graduate student and looked for worms that would live longer and she mutated them and found a strain of worm, a mutant worm.
10:53
That was living twice as long. So instead of living for 15 days, 30 days and that was a remarkable finding because when she defected the worms bread them out, found that it was due to a single gene mutation. And when she cloned the Gene and found out where it was, it was in a gene that sends insulin, the insulin receptor Gene called daf-2, that was remarkable because it had nothing to do with free. Radicals had nothing to do with DNA damage. It was a signaling molecule.
11:22
And that was the start of a revolution in understanding how to control aging by using genes and supplements and drugs that turn on the body's defenses.
11:33
And this was the first so-called longevity Gene.
11:35
Yeah, I would say that was the first came very close to the work that we were doing at MIT. We were maybe a year later than her. But
11:46
we are you seemed a little annoyed by that
11:47
not so much me. I'm careful because my supervisor Lenny guarantee used to get really
11:52
Annoyed when he was told that he was slightly behind, he thought his work was being done at the same time. So those two used to be the I guess maybe still are the at the Forefront of this field. They're certainly the grandparents if nothing else and they both both showed so Cynthia and worms and then Lenny in yeast where I was at MIT made the finding that a single Gene alteration can have a huge impact on an organism's
12:21
lifespan. And these genes are
12:22
There's a few of them now that we've identified and they all of them seem to work on a very similar circuit that all starts with adversity.
12:31
That's right. These signaling proteins like the deaf 21st discovered and the sirtuins that we work on. We didn't know what they were doing. At first. I was like, this is crazy. It's got nothing to do with DNA repair and free radicals, but then when we tracked what they were actually doing it turns out there, speaking to the rest of the cell to keep the cell healthy and alive.
12:53
So, in the case of that worm, those worms won't just longer-lived. The program to survive was activated. Those worms are stress resistant. You can hit them with heat. You can hit them with cold. You can star of them or just put them in happy conditions. They live longer. This, the Paradigm is that normally a worm response to its environment. If it's starved, it'll hunker down, it'll survive. But here we had a worm that was mimicking. Starvation.
13:21
And was able to have the benefits without having having to starve itself. How how
13:26
do these jeans for lack of a better word? Know, how do they know that the conditions are adverse and they need to turn on.
13:35
Well, there are various sensors. And so the three main Pathways, that control this. We've talked about mtor, which is sensing the levels of amino acids in the cell lower levels of certain amino acids, Branch chain. Amino acids are good for the cell because
13:51
Down-regulate mtor activity, that's one way. The MBK responses energy, glucose and then the sirtuin sends NAD, which is a molecule that goes up with exercise and hunger together. Those are the sensors now. How does a cell communicate with other cells? Well, there's insulin like, we know when we eat a meal, insulin goes from our pancreas, into our bloodstream, and tells the rest of the body. Hey, you got sugar already. Suck it in, use it. That's a signaling protein. And what Cynthia's worms ended up.
14:20
Up when they were mutated is that that signal to bring in the glucose was mutated. And this insulin signal was absent and when don't have the insulin signaling in your worm, it means you're hungry and you get the benefits of being hungry without having having to starve.
14:38
So, our body is this always active monitoring system, were perceiving the world around us and the world around us is constantly throwing different stressors at us.
14:50
Or at least it was in human history, right? We've always been a little cold or a little hungry or a little scared or having to run from this animal or that animal that wanted to eat us. This is the environment that our species evolved and it all species evolved in, right? Is this constant state of
15:09
adversity? Right? And that adversity, we've evolved to fight back. And so, in the past our bodies were constantly fighting disease and deterioration throughout life even
15:20
For birth, we're fighting against entropy things are falling apart. The Aging clock that we can now measure begins at conception. But if you fast forward to, now our society is built on Comfort. We've got most countries, have enough food and shelter, we can sit down, we don't have to run away from predators very often. And this is a real problem because these longevity defenses, that normally would be activated by being cold and hungry and running are lethargic. The body. Doesn't
15:50
Spend energy to defend itself. Unless there's a need for it and modern society is the worst thing eating. He could waive those needs. Yeah. We love Comfort. It feels good. But that's the worst thing for long-term Health. We need to trick the body into getting out of its Comfort Zone by doing these things. We've talked about eating the right Foods including foods that are stressed eating less often
16:13
which puts stress on us which causes your body to feel like it needs to protect itself because if we're not
16:20
Filling it with all of the nutrients and calories. We want it perceives a need it, precedes adversity. And it turns on these these
16:27
jeans, right? And as long as we have adequate nutrition, that's what we call it intermittent fasting with adequate nutrition or ifan. This is another term. We just coined in this podcast, that allows the body to turn on these defenses without suffering, long-term negative consequences. What's interesting. I find is that even though we know the fridge is probably full with food, our bodies are not that smart, our bodies. Don't get that.
16:50
Message and we can trick it trick the body into thinking. Oh my goodness. The fridge is running out of food or the field or the forest is lacking in food. We better get to hunker down and survive. What are those things you burn fat? You increase your metabolism. So you've got more energy to run around and find food, you become more alert because you've got to go find more food and you defend your body against insults, whether it's incoming infections, or diseases from within. And that's cool that we can trick our bodies and it's
17:20
That hard, we just need to do the things we're talking about on this
17:24
podcast and and what we're talking a, you know, we've already talked about like, the the real key effects that come from eating less often to basically turn on this adversity, mimetic effect. There's another really easy way to do this though,
17:38
right? And that's Get Off. You Buck just get off your butt. Yeah, it's not that hard. As we say, sitting here doing this podcast, but one way I do it is I have a standing desk, so my butt.
17:50
Actually atrophied when we were writing this book lifespan, I ended up with a cramp in my piriformis muscle which is the way that your own your what? Yeah. Yeah. It's it's a small muscle. Where is this ice? Doesn't matter. It's right in your hip, it goes through that hole in your pelvis and it's essential for standing and it was trapped under without whole was for. Yeah,
18:12
it's, there's a muscle that goes through it. Yes.
18:14
Okay. All right, and then so, but it was cramped up on my left hand side. So I was limping for about nine months.
18:20
After we wrote the book and I thought a great, you know, I'm writing about Health and Longevity enough now crippled crippled myself. I eventually got it to go away with the combination of exercise physiology and an injection of NAD and my butt, which we'll get to in probably the next episode. But the point here, is that sitting down is bad for us. You atrophy, you have less muscle, which means your hormone levels, special, particularly testosterone will go down and you become
18:48
You know, in pain, that's not a good thing. But ultimately, if you have not a lot of muscle in your hips, particularly, you can break your bones when you fall over when you're older and all of, that means you need to get off your butt stand up. Even better go for a walk. Even better go for a run or cycle to get what we call a hypoxic state going. Your body needs to suck in more oxygen and that has Remarkable Health benefits, and we really have to work hard
19:14
at this because I mean you're saying this as we're sitting in these chairs right? A couple of days after I sat down
19:18
I'm going to share for a long time in an airplane to get here. Right? We've got a nice comfy couch over there that we've been working on, like, we actually have to actively like pursue opportunities to do this, to get this to get exercise to promote this adversity, mimetic effect, because our lives are built around comfort and sedentary
19:39
- yes, that's true. And what I think most people don't appreciate is that exercise isn't just beneficial for your Fitness and for you?
19:48
Vitality. It actually can stop diseases in their tracks exercise can slow down cancer. In. Fact, it can prevent up to 23 percent of all cancers from occurring. That's true for cardiovascular disease. In fact, it has an even bigger effect on that 30% reduction, just by doing moderate exercise every week. 50 minutes is sufficient or three times a week with ten minutes all-cause mortality, right? So what we are all cause mortality is based, mortality, is basically slowing down aging, that's it.
20:18
Twenty-seven percent reduction in the rate of Aging just by
20:21
exercising the thing. You just said, I love this idea of connecting, the idea of all-cause mortality with aging because as we've presented here is you've been arguing for quite some time, most diseases which bring us toward the end of our lives are really just an accumulation of the symptoms of aging. And so if you bring down the disease rate,
20:47
Across various diseases, which is bringing down all-cause, mortality. You're really just, it's just a another way of saying. We're bringing down aging,
20:56
we must be exactly. And we can also. Now, measure that, with the biological clock, the so-called Horvath clock named after my good friend Steve Horvath. That is a, now a measure of the process that leads to all of these diseases that kill us. And one way that we know for a fact to slow down. The ticking of that biological clock is
21:16
exercise.
21:17
And any kind of exercise is good. This is why the 10,000 steps a day goal is popular. Generally speaking. It's good. It's not a magic number. I think there's somebody came up with 10,000 and actually some Studies have shown health benefits that are, you know, existed for to 6,000 kind of Peter out from there. But but the basic idea here is that we move we burn calories. We're putting our bodies into
21:47
into a, at least a low state of adversity,
21:51
right? So try to get four thousand and ten thousand seems to be even better.
21:56
It's a great goal. It's a round number. It's fine. Just
21:59
get off your ass. That's what we're saying. That's all it takes. It's not that hard. Walk around the block a few times and particularly after a meal. As we spoke about last time, walking after a meal, gets your glucose levels to be more level, which is what you want,
22:11
what it relates to this over. The we were talking about this old Chinese proverb, 99 steps after a meal and no,
22:17
Steps after meal, you'll live to 99 but walk after you eat. Right?
22:22
Because, well, it'll stimulate the uptake of glucose. But also it'll get your muscles moving and stimulate the production of new blood vessels. Make sure that you don't run out of oxygen later in life, but mostly what happens when you move. The first thing that happens is a really important reaction that involves one of these longevity Pathways the middle one that I refer to called
22:41
ampk and we can, we can turn on ampk just with a low level.
22:47
Level of exercise, just just start that
22:49
adversity. Yes. OMG K registers energy in the cell, which is chemical energy called ATP. And when you have low levels of ATP ampk gets activated and it stands for a MP activated kinase and A and P is what you get a lot of when you don't have enough of this fuel ATP, long story short, when you have high levels of ampk activity, you will make more mitochondria, which gives you long-lasting benefits, so,
23:17
After you've exercised, your body will be making more power, more of these. These organelles. We call them that will actually give you long-term health benefits beyond the period of exercise.
23:29
We know that low level exercise alone is good. It's a good start. We also know that it's really not enough, you need to also be getting a pretty consistent dose of vigorous exercise to. It doesn't have to be a lot of
23:47
Studies show, you know, 10 minutes a day, 15 minutes a day, even even 15 minutes a week. If you're getting started is going to have health benefits, but vigorous exercise, the easiest way to think about it is your breathing. Your breathing rate goes up and your heart rate goes up. Right,
24:03
right. And that there's a reason why vigorous exercise is so important Beyond just just walking and standing. It's that you have hypoxia low levels of oxygen are undoubtedly good for you even though they may not.
24:17
Feel good. And when, you know your your hypoxic when you're painting so much, you can't cannot carry out a conversation. That's what you're aiming for, for at least 10 minutes a few times a week. So, why is being out of breath important. Very rarely people ask that. Well the main reasons
24:33
it doesn't seem to make sense on a state like you need oxygen,
24:36
right? So again, it's this hormesis idea. A little bit of what doesn't kill you makes you stronger. So what's happening is when your hypoxic is your turning on what's called f 1 Alpha
24:47
A hypoxia-inducible factor and that pathway turns on a bunch of really helpful genes that control on you blood, vessel growth. And mitochondria, my good friend and colleague over at Harvard won. The Nobel Prize in 2019 for discovering if one alpha and its role in biology. Now, the other thing that happens in that those two things, so one is the point out for the turns on a genetic program. That's good. But what also happens is, you get free radicals generated because when you don't have enough oxygen, those
25:17
Is that, that should normally be used by, What's called the electron transport chain in mitochondria, which generates ATP, they fly out and they become a super oxide
25:27
radical. Can we, can we talk about that electrons? Because it's really fascinating how this thing works and it is like, it is a little circuit around.
25:34
Yeah. Yeah, that's a little bits. A little battery made of proteins, and there's a string of proteins. That's that come together in the membrane and they pass along a an electron, like a hot potato. They don't want to hold onto it, they shovel.
25:47
Ang get rid of it, get rid of it and in doing so they're pumping protons which are hydrogen atoms into the inner membrane space because there's two membranes that surround the mitochondria and in that little space, the goal is to make it really acidic by putting in these protons into there and this electron transport chain does that. But you need oxygen because at the end, when you get to the end, you got to get rid of this electron and they give it to oxygen. Okay, and then that's called respiration. It's reason we need to breathe so hard. When we
26:17
We when we run and why we need oxygen in the first place. Now, if you don't have enough oxygen, then that'll lead to these free radicals being produced and it will damage the cell. So you might say well that makes no sense. If you're running and you're damaging the cell, it's going to be bad. Right? But remember a little bit of damage can be good. So what happens is it stimulates? What's called? My toe hormesis mitochondrial hormesis and that has a whole variety of benefits as well, including the manufacture of more mitochondria.
26:47
That gives you energy, but I want to mention something. That's really interesting. I think about this electron transport chain. Remember, how I said, those protons, those hydrogens get pumped into that little space to make it acidic. So that now you've got what's called a gradient. You've got more of them in that space than inside the mitochondria in the in a bubble. They have to want to get out. They if they got too much somewhere. They should equal liberate. And what the cell does is it puts little holes that the protons can escape through a little bits.
27:17
It's called the ATP Hayes. And what happens is, well as those protons shoot through, it's like a hydroelectric, Dam turbine and as they shoot through, it literally spins, like a turbine. There's a little wheel at the bottom of this tube that spins Superfast, many times per second and that spinning allows it to make ATP or chemical energy, which then you use then to burn to make the muscle work. And so what's really interesting. Is that the more
27:47
Mitochondria, you have, if you've been exercising for a few weeks allows you to make more chemical energy and you don't feel puffed as much as you do it before. And the other thing that's happened. Besides having more mitochondria is that you've built more blood vessels in your body. And so your oxygen gets transported to the tissues. Now, both of those things go awry as we get older and we'll talk later and tomorrow about how you can circumvent that and reverse your age to be able to regain that ability
28:13
with drugs molecules and
28:15
supplements, besides what,
28:17
Talking about today exercise
28:18
itself. Yeah, we keep going back to this idea of a little bit of adversities give her. Like a lot of is going to a lot of anything is going to kill you but a little bit of a lot of these things that might in big doses. Kill you is really good for us because it puts our bodies into the state of adversity. Let's talk about this in terms of another effect of exercise, increased glucose
28:41
sensitivity, right? So that as you get older our muscles and our brain become less sensitive to the environment,
28:47
Excellent. The pancreas is putting out increasingly more and more trying to cope with this insensitivity that happens. Now, that's largely. We think now because of this aging biological clock that the genes that are required for a muscle cell to function or a brain cell to function are getting switch on and off in the wrong way. We call this x differentiation and if you didn't see episode 1, you might want to go back and hear more about that basically cells are losing their identity as they get older and not putting out a particular protein called gluten for which is a
29:17
Glucose transporter on the outside of the cell. So the muscles are not bringing in the glucose. There's two Problems by first of all, you don't have your energy to burn in the mitochondria to make energy. The other problem is that, that Sugar like glucose that circulates in your bloodstream, and doesn't get taken up into your muscle and your brain starts to damage the lining of the blood vessels. And we know what that is, type 2, diabetes, and cardiovascular
29:38
disease. And that's where veg F comes in.
29:42
So, vegf is a little protein that signals the
29:47
In of new blood vessels when you exit call this adventure F by D capital V EG
29:52
F. Okay. So if you want to look this up, yeah. Yeah. Okay. Alright. So vegf.
29:56
So, vegf is made by muscles after you exercise you've gone for your run or even your walk, but running is even better and there's a gene called PG. C, 1 Alpha that is what's called a transcription Factor. It'll be made. It will bind to the Upstream side of the vegf Gene and make more of this vegf protein. Now vegf will
30:17
Be secreted out of the muscle and diffuse or just leak out into the lining of blood vessels. Now, the lining of the blood vessels is made of cells called endothelial cells, which pick up the signal, they have little receptors that sense vegf and when they get that signal that says, oh, wow, we're being chased by a saber-toothed tiger. For the last week. We better build more blood vessels and they do that. Normally, if you have a tube, which is a capillary almost microscopic.
30:47
Blood vessels. What happens is the endothelial cells will start to Branch out to the side and make a new blood vessel. And that's what you get with exercise. Conversely. If you sit around all day, you won't build new blood vessels. You'll actually have fewer and fewer and your muscle and your brain start to get starved of oxygen. Now, one of the big problems we discovered is during aging that signaling pathway that signaling mechanism is defective. And even though you're exercising, as you get older, you're not getting the benefits of it. You don't get the new blood.
31:17
And you can see this in a mouse. I mean, when you take when you pull the mouse apart, not to be too graphic, but you can actually see these thing.
31:25
We don't even need to hurt the mouse to see this, we can use Imaging to see the blood flow in a mouse without hurting it. And we can see the bright red areas where the Bloods flowing nicely in an old mouse. You don't get that even with exercise, but we found a way to restore the Youth of the muscle and restore the ability of that vegf to trigger new blood vessel formation.
31:47
Operation. And the trick was to turn on the production of NAD, which is the fuel for the sort of to ensure survival circuit,
31:55
which can be turned on by exercise because exercise upregulate and ampt.
32:01
It also known as an MP t-- man PD. Some people call it that. But yeah, this is the relative of that ancient yeast Gene that we talked about in our first episode, that extends lifespan of yeast cells.
32:13
So let's add one more piece to this and
32:17
Is how exercise impacts the
32:20
epigenome? Yeah, the epigenome. If you missed episode 1, I encourage you to go listen to that and watch that because we covered what the epigenome is and how it affects the aging process. But the summary is that the epigenome is the regulator of the DNA. It tells the genes whether to be on and off and that goes wrong during aging and may actually be the reason we age. And one of the reasons we believe that is that you can measure biological age. Now, in people, I could take one of your cells map.
32:47
Back to my lab. Well actually have to take a chunk of your cells or a cheek swab and we can measure the rate of your aging. It's called the Horvath clock or DNA methylation clock. And when you look at people that have lived a healthy lifestyle say, they've been exercising for the last 30 years. They are much younger epigenetically according to this clock then someone who hasn't. So that tells us that very likely that exercise is not just protecting you against cardiovascular disease. It's slowing down your overall rate of
33:15
Aging, there are other
33:17
As well, one of the many actually. Yeah, so our one of our researchers, a diva Johnson was involved in this study that used the proteomic clock, which works. Similarly. Let's talk about that really quick because it's another way to measure biological aging,
33:30
right? So, do you can measure proteins in the blood which change predictably over time? There's a protein called gdf 15, which is circulates now, a really great biomarker for Aging. In fact, GD, 50d F-15 is one of those genes that was used in that study. We refer to
33:47
Two last episode, where the Mediterranean diet, slow, the aging process. They found that gdf 15, the methylation on that clock marker was also slow down the point here. Being that these proteomic clocks and the epigenetic clocks and some others like, an immuno clock. Can be used now to understand what slows down aging. But importantly how do you reverse it with various treatments? And we've gone from a field where we had no idea what was going on in aging really? We had to look at
34:17
Of thousands of people on Metformin to see if it helped Health to a point where we can take 100 people treat them with something. Two months later. See if they've gotten younger or not. And those experiments are being done right
34:28
now. And one of the things we could treat them with is exercise exercise in the study were just talking about. They looked at aerobically active people versus sedentary people and the aerobically active people were five and a half years younger on average. According to this proteomic biological clock.
34:47
Presumably, we'd see the same thing if we use a Horvath clock or an immuno clock.
34:51
Yeah, and that's true. Actually, it's been done on exercised people. And they are also epigenetically young. And what's important about this clock to realize is that it doesn't just tell you, your biological age. You can actually predict when you're going to die when someone's going to die. And when I say that a look, some people probably do a little more people that I don't want to know this. Well, consider this that 80% of your future health is in your own hands. It's, it's modifiable 20 percentage.
35:17
Liquid you can't do much about yet. That's powerful. We if you have the tools to change the rate of aging, first of all, you have to measure it to know if it's working. So I recommend that and we'll talk about ways to do that practically. But if once you have that number then work with me, we can tell you here in the podcast how to actually slow and reverse that
35:39
process. Well, and we use car analogies a lot you and I think a lot of people do these but it Bears mentioning.
35:46
Like you know that your car is not going to last forever, you there's a shelf life for any car, you get to choose based on how you treat the car over time. Whether or not the car is going to last. A hundred thousand miles or 200,000 miles, or
36:00
three or four hundred thousand take it to the body shop repair any mechanics more often. That's what we're talking about for our bodies. And that is why do we will you need to measure it. You need to know when the car needs a service, you need to know if if you're tweaking that knob whether you're doing harm.
36:17
Good. And to that in one of the really cool and exciting development. That's happening right now is there's this sort of race for these clocks to become available widely for people to use so much. So that the, the price point is predicted to be what like a buck.
36:40
Well, it's coming down with a horrible time for a Horvath test, right? So right now, if you want to check your biological age, you can go to inside tracker.
36:46
One of our kind sponsors, that's a, that's a blood test. Or you can also have a DNA test, which is available by for a few hundred dollars from various vendors. A student in my lab Patrick Griffin. We've posted recently a paper, which can be excessive accessed on Bayou archive.org. That describes a way to pull put together thousands of people, samples and run them all. Together bringing the cost of that test down to less than a dollar, which is means that very shortly in the
37:17
Sure, when we bring out this product and we are bringing it out soon. You should be able to do this test routinely and see whether you try new diet or a supplement or just meditation, whether you're actually benefiting from that.
37:31
A lot of people here, all of this and they go, okay. I get it. I have to exercise, but and I hear this a lot, but I hate to run like everybody thinks of like that's the only thing they're allowed to do. And I think doctors make Android physicians may contribute that to this a little bit by saying like, Okay. Well, I need to continue running and jogging or whatever. It's not just running, right? Like it. What's the best kind of exercise?
37:54
Well, there isn't the exercise. You're going to do what you love doing and it can be a sport it.
38:01
Be windsurfing. It could be sailing but just move. That's the main thing. There's even, there's even sex, which is we actually look this up.
38:11
We are really hopeful when we look this up and it burns like for calories a minute or something. It's not as good as
38:18
well. I'm sure it depends on the individual, right? I mean, you can
38:22
make sex more aerobic. You can make it part of your exercise regimen, but you have to have a partner, a consenting willing partner who also wants to make it part of their
38:31
Exercise regimen only 4.2 calories per minute which were on and we also looked up the average length of sex and it's about five
38:40
minutes, right? So you better burn 20 calories. If you're an average person, I'll burn
38:46
10. So instead of that. You probably need to go for a longer walk afterwards to really burn off those calories and get your blood
38:53
flowing and however, you get your exercise be it running or sailing apparently or sex both.
39:01
The World Health Organization, the Mayo Clinic recommend at least 75 minutes of vigorous exercise a week. So that's 15 minutes a day,
39:10
10 minutes and it's better if you spread it out over the week,
39:13
right? Yeah, you don't don't do it all at once, but that's that's the starting point and most people can do that. You can be the busiest person in the world. You can be the most unhealthy person in the world. You can get your heart rate and your breathing up for 10 minutes a day.
39:28
So, you can, and the benefits will be huge. You'll feel better.
39:31
You'll look better and you'll also have a better resting heart rate. That's one of the best measures of your Fitness. If you're less than 50 for a resting heart rate. That's really good for someone my age in my 50s mine. Mines, usually around mid 40s. That's a good indication of how well you're doing. And if you got a high heart rate, it's you're either to stress. So you are unfit, try to bring that down again. You can measure your heart rate, pretty easily, just put your hand on on your arm, but you can also either way a ring or new fitness these these
40:02
Wearables. Now they're gonna help you do this.
40:04
Yeah, and I'm a big proponent of measuring things, right? Because otherwise you're Flying Blind, so I wear a ring, I wear a wrist. Watch, I sometimes wearing right now. I am. This is also measure sleep, which we'll get to in another episode. But I also there are some Advanced bio monitors. We're also going to cover. There's one that I stick on my chest for two weeks that measures my body a thousand times. A second for various parameters, including my heart function, and in the future, these will be used by people to predict heart.
40:31
Attacks, as well as the flu and all sorts of issues, like, depression in the future. We're not going to be Flying Blind. We can be monitored a thousand times a second as opposed to now where you go to the doctor once a year and they spent 15 minutes asking you how do you feel which is a joke?
40:45
Right? Right. Because in addition of the fact that it's a single, it's a single assessment of single time. It's highly subjective itself reported, this just crap
40:55
data. Yeah. This is a bit of an aside but it's worth noting here that I've been measuring myself for
41:01
Ten years using inside tracker. And that data is wonderful. It's graphed and it you can see when things go wrong. I've corrected that corrected it they do an inner age study. There's a measure called inner age 2.0 which tells you how you're doing compared to others your age and you try to keep that low. And based on that calculation. I've been getting younger for the last 10 years, which is great to talk about. But it also means that I'm optimizing my body. Every time when I do something, and if something doesn't work, then I won't.
41:31
Do
41:31
it and we are going to get into this but I do want to like I've Got a Friend a price who helps people do this, The Institute for systems biology and they help people like create these charts that they could then bring in to show their doctors. And he was telling me about this woman who brought her chart into the doctor. The doctor was at first dismissive and she said, well, won't you at least look at it? And the doctor looked at it when
41:52
oh, wow, this is really helpful. That's exactly the response of my doctor to my doctor said, well, how do you feel?
42:01
I'm good. I'm sleeping. Well, and he said, okay. See you. Next time said no, hang on. Let's do some more. I've got some data. Can I show you and I showed him the inside tracker data on zoom? And he said, this is wonderful. I wish all my patients had this data, of course, he cut cannot order, 43, biomarkers, every time the that's a health insurance won't pay for it. But individuals, if they want to spend their money instead on instead of coffee. They can put it into a blood test. Doctors actually due respect those data because they're actually produced by the same companies that the doctors would use anyway,
42:31
And and to bring this all back to take this all back to exercise and these other adversity memetics, which we're going to get to having this data. I'm big soccer fan. The first time I saw soccer player, trike off his shirt. He was wearing a bra, and I thought what the heck is going on, but it's actually holding these trackers that are measuring things in the middle of games. In the middle of practice, is the world's best athletes are doing this right now, and it's becoming more and more available for other people to track as well. And once you have this data, you can start to act on this data. You can
43:01
Or to arrange your exercise routine, so that you're getting the most out of
43:06
it. Exactly. And they can be fun to use GPS to see where you're going. You can compare it with your, your colleagues, your friends. I'm running more than you.
43:15
Let's move along here because we've got a lot more to talk about, but before we get away from exercise and start talking about these other adversity memetics, there's another form of exercise that I'm going to you enjoy that. I enjoyed a lot of people enjoy but maybe doesn't get
43:31
As much attention as aerobic exercises, weight
43:33
training will add. You said that. All right. So weight training. Yeah, I do that. Fairly often. I would say at least every other day. If not every day, the way I do that is I have a gym in my bedroom and also have weights next to my
43:47
desk. You also have them in the trunk of your car right now. I thought
43:49
I do it because I travel a lot, so I'm taking weights with me. But the reason that I do weightlifting is that it's going to maintain my hormone levels. It's going to maintain my ability to
44:01
Walk, well and stay upright and have good posture. It makes me look better. Although you may say that's debatable. But also, as I get older, not debatable, you're really good-looking guy, David. Thanks. You only lovely, Matthew. Thank you. The other thing is that, that is often not appreciated is it's harder to build muscle as you get older and you want to maintain that muscle mass. I'm losing about 1% of my muscle mass every year, unless I maintain it or build it up as you get older.
44:29
You're going to fall over, right? Everyone Falls over especially as they get older and if you break your hip that's close to a death sentence. A lot of people. Well, 19 people every minute fall over and break their hip in the United States, which is a major cause of mortality.
44:46
In the mortality rates, after a hip break just like Skyrocket.
44:49
Well, it's equivalent to having metastatic cancer. That's how bad it is. But if you've got muscles and your flexible, you do say Pilates in your older agent and
44:58
Which build up the muscles? Particularly around your waist, then you much less likely to break a bone when you fall.
45:05
Yeah, building muscle mass also helps maintain youthful hormone
45:09
levels, right? So I had trouble maintaining testosterone levels like most men, my age now, there are two ways to go about it. Generally. The main one is that your doctor will give you an injection of testosterone to to apply at home or a cream that you can rub on your forearm. Those are the two ways you can do it.
45:27
There are others. But the other way which I prefer is to naturally boost it by maintaining large muscles, exercising my thighs, my butt my back and I've compared the two, I have tried cream on my arm for testosterone, it worked. Okay, I've levels went up maybe by 20% wasn't great. I really maxed out my testosterone levels by doing leg exercises back exercises. I'm talking about things like leg extensions leg.
45:57
Girls, as well as hip hinge, which is bending at the hip and lifting weights. And I also do deadlifts which is standing up with lifting a really heavy weight with a straight back.
46:08
There's another way that we know that exercise is impacting aging and we talked about senescent cells in terms of what iron may be doing to cause cells to go senescent. But let's, let's talk about that as one of the
46:27
Aki aging, what is called the Aging Hallmarks exercise, prevents senescence, it turns back citizens. What's exercise doing in terms of these zombies hell's
46:38
will you? Let's start with what is innocent sellers. So when the epigenome becomes to dysregulated in this x differentiation process happens cells can either die, they can become a cancer. But what the body tries to do is to prevent that, by shutting these cells down and make them more, like, zombies, they were alive, but they're not dividing and they causing Havoc.
46:58
And greeting. All these chemicals and of the
47:00
bloodstream, they are it's called thus. ASP the senescence Associated secratary phenotype, and these proteins cause inflammation. They also cause cancer. So the fewer senescent cells you have in your body, the better. And we're starting to find that there are that lifestyle and supplementation and some drugs can slow their formation. Remember, keep the iron levels low, but also we can kill them off. And there's this study are the one you're referring to.
47:27
Each
47:28
took 34 individuals for a 12-week exercise program and looked at the amount of senescence cells circulating in their immune sin, the blood immune system and it was dramatically lower in the exercise people arguing that you can actually kill off or reverse that process 12 weeks.
47:45
Just 12 weeks is 12 weeks to, like, destroy some centers and soul seems like a pretty good deal.
47:50
Yeah. It's one of the best ways to kill off senescent cells.
47:53
That's the study that was just out this year in Beijing cell.
47:57
England at all. We will link to that in the show notes. Let's put a wrap on exercise, but let's have a few takeaways here and there's really there's three big ones. The first is a low level of exercise and and this is just steps right? Get off your butt, get off your butt and take ya
48:18
standing desk or a desk with a treadmill. Walk around the block after dinner or lunch. Those are the simple
48:25
things and you don't have to hit 10,000 steps, but
48:27
44, 44 is great. Okay. All right, and then that's the low intensity exercise that everybody should be getting throughout the week every single day. You should also get high intensity
48:38
exercise for sure. A few times a week 10 or 15 minutes lose your breath. It can be the form of hit high intensity interval training or running on a treadmill. That will get your blood vessels flowing and your mitochondria amplifying
48:51
10 to 15 minutes a day. Yeah. That's a 35 minutes a week.
48:55
Yeah. That that's what all the experts.
48:57
Okay, alright, and then muscle building.
49:01
Yeah, weights. That's just as important. So, maintain that muscle mass for your hormones testosterone, particularly for men and women exercise, the big muscles, particularly. Don't forget about those. Don't just work on your upper arm. So you look good, but it's pretty simple. You don't need a gym in your bedroom. Like I do, you can do push-ups sit-ups or just have some weights lying around, that's
49:21
sufficient. Okay, and all of this is the goal is, it's not just we want to look good. We want it right now.
49:27
All of this is aimed toward the goal of longevity through, putting your longevity genes into or alerting your genes your cells to a state of adversity.
49:39
Yeah, the adversity,
49:40
memetics University of Memphis. I really do like this word. I think this is going to catch
49:43
on. Yeah, we trademarked that one rub.
49:46
Okay, so look, but this is not the only exercise is not the only adversity. Mimetic. There are others. We're going to talk now about a few other categories. We're going to talk about
49:57
out, cold temperatures are going to talk about heat, but there's a really exciting one right now and it is related in some ways to exercise or the effects, the genetic effects. The, the cellular effects that we get from exercise and its really fast moving. The latest studies are only out in the last couple of years. And this is hyperbaric oxygen
50:16
treatment, right? Or HBO T. Yeah. This is really fascinating because for a while we knew that wounds repair or heal faster when you give them or oxygen, because
50:27
Why? Well, it's not not clear. It could be hormesis free radical generation. Could be that more oxygen in the tissues allows them to grow better. Those are all theories, but we know that it works but then people started putting themselves in hyperbaric chambers the military certainly. The Navy of have been doing this for a long time to prevent the bends, but it's bound to be quite therapeutic. Particularly for neurological disorders. Been increasingly for aging
50:54
itself, and we should say what a hyperbaric chamber. Is I prepared.
50:57
Chamber is it is a room or sometimes? Just a little tube where the pressure is increased. And when the pressure is increased, the amount of oxygen that you get, when you breathe is increased,
51:09
right? You can go up a couple of atmospheres or more and you, and you supplement that with oxygen, you breathe in bit more oxygen, or pure oxygen. And so, I recently tried this actually, I went out to LA. Fortunately unlike you I'm not
51:23
claustrophobic. I'm so glad I can do this. I cannot do
51:26
this. You probably can't. But
51:27
It's a glass cylinder, so you don't feel it. And I just watched shits Creek for a while was pretty cool. Especially when I was high on oxy
51:33
said it was funnier. When
51:34
you, it certainly was funnier, but I might just be because every time I watch it, it gets funnier, but, but it's really relaxing. I believe, I was in there for about an hour and it was, you know, you can meditate in there or you can fall asleep or watch TV. It's really a great experience. But that aside, what the science says is that it actually can reverse an aspect of Aging which is teyla.
51:57
We're shortening, the ends of the chromosomes. Many of us will have. You will have heard of this, like the ends of the shoelaces, the aglets, they're called, if they wear out, it actually leads to Cellular senescence, the zombie cells. And this happens over time as we get older. And what we've been looking for. We scientists for many years as a molecule or treatment, that makes them grow back again, because that should help slow down aging and give us longer life. And that's what was reported last year from a group in Israel who I know. Well, I've been over there and
52:27
I doubt they're giant chamber
52:29
and you also got wind of this before while they were working on it and you into kind of like peek in on what they were
52:35
doing. Yeah. I mean, this is one of the fortunate things about my job is that I get to hear about things before their public and I get a sneak preview and I went over there and sat in their drying chamber, which looks like it the inside of a bus and with a mask you put on and they showed me their data actually looks like a control room from Star Trek. It's really high tech and but the data that they showed me in mice and in
52:57
It's was really compelling. It looked like at least in the mice that those plaques and tangles in the brain of mice that were given Alzheimer's, went away to have a little miniature hyperbaric chambers for the month. We're building one because I'm going to use one in my lab, but they're not ready yet. But also what they were finding was that the humans that were put in there that had Dementia or Parkinson's were dramatically improved after a few sessions of this and it's become a real craze throughout the u.s. Lat.
53:27
Of this is happening in La where a lot of these Trends start people are reporting remarkable benefits. Now what we need are more studies like the one in Israel to actually measure things and and if possible do a placebo control as
53:39
well, but at least what we have right now are some studies. Most of them fairly small scale, but but human studies memory improvements telomeres T helper
53:51
cells.
53:53
Right, they go up as well. So that and cognitive performance. There was six elderly patients suffering from memory loss and in 2020. And this new study came out and they all improved.
54:02
And the really cool thing about this treatment, even though look like not everybody has access to a hyperbaric chamber obviously, but it is a pretty easy intervention and it's easy to treat people this way. It's easy to test people in this way.
54:20
So now we have the clocks. We have a clock so we can test
54:23
Of Beijing actually goes backwards. That would be a good experiment is to take people who have done seven or eight ten bouts of this treatment before and after and see if their biological age went backwards.
54:35
So it's still early. It seems like these things are working across a variety of ways that we can measure Aging in the problems of Aging. If this is working, why is it
54:45
working? Yeah. Well, we don't know for sure but one of the theories is that it's working similar to exercise. So
54:53
Are the low oxygen when you go for a run? What it's doing is turning on this f. 1 Alpha protein that I talked about earlier and that helps promote Health in the body. The other thing that happens with exercise is the free radical generation. That gives you a little bit of my toe hormesis. It looks very much like hyperoxia.
55:14
Hyperbaric chamber treatment does the very similar thing. You get a production of these free radicals and that stimulates also a miter hormesis response that gives you very similar benefits to low oxygen. There's one theory of that I have is that when you come down from the high levels of oxygen, it stimulates simulates hypoxia, like you're running as you come down from high levels too low levels,
55:38
so it doesn't much the oxygen and the like explosion of oxygen that you're getting. But it's like, once you
55:44
Temporarily get used to that, then
55:46
come off. It's the differential and that fits with the new findings, which is going up. Once, and coming down once is not as good as going up and down and up and down within a
55:56
treatment. Before we move away from hyperbaric oxygen treatment. I know you're most familiar with this Israeli study. Let's talk about the protocol in that one.
56:06
Yeah, they took 30 people and put them in their large chamber. The one that I visited and they did 60 daily sessions of 90 minutes.
56:14
Five of those per week and had a look at the number of senescent cells in the bloodstream before and after and telomere length, and what they found remarkably was that those aspects of Aging were
56:23
reversed. They saw impact on senescent cells.
56:26
To they did they looked at in the immune system, looking at looking at these immune cells. You can measure senescence, you can stain them blue, which is bright blue. When you get older and they found that there was a dramatic reduction in the number of those senescent, cytotoxic T cells as they're
56:42
called. Okay, so
56:44
SI sessions 90 minutes. This is not something anybody. Most people can do everyday right now. This is not going to be a common part of people's longevity regimens anytime soon.
56:57
Well, there are a number of centers that are run by doctors in major cities. It'll become more popular. It's growing rapidly, but I think it's a great way in the future for people to mimic exercise. I wouldn't say don't exercise, right, but it's an interesting idea that you can lie down.
57:14
Down watch TV, go to sleep and get your your run-in by mimicking hypoxia. But in this case with high levels of oxygen in your body for a short period of time,
57:23
really cool. Let's shift it now to talking about cold therapy, which is another thing that a lot of people experimenting with. Now another thing that there are centers for all over the place, but that the research is still sort of catching up to the excitement. So we're not we're sort of on the edge.
57:44
Here of our understanding, but we do know some things about what cold does to the human body. And actually what cold does to organisms across the Spectrum.
57:55
Yeah. In fact, when we wrote lifespan there was almost no data on this, but now, we know actually that one of the huge benefits you get from being cold, is the production of brown fat. So, what is brown fat, Brown fat or often called beige fat is found in babies. It's typically to allow them to stay warm because they
58:14
Don't shiver until they're about one year of age and what was discovered about 10 years ago at Harvard by Bruce spiegelman and Ron carne a couple of my colleagues is that adults also have some brown fat and they discovered this with with pet scanning and they found it. Mostly exists on your back in your shoulder blades. And when you get cold it revs up, you get more of this brown fat and this is a good thing because Brown fat is extremely healthy. It revs up metabolism it
58:44
One's white fat, and we think that there are these factors little chemicals, little proteins that get secreted out of brown fat, that make the rest of the body healthy as well. One of the reasons we know that is because there's a gene that makes brown fat makes cells turn brown from white to beige brown, and it's called PR, DM, 16 and mice that lack. This gene. They don't have brown fat, but they also develop type 2 diabetes and cardiovascular disease as a
59:10
result.
59:11
Hold impacts, not just humans and impact follow organisms. We've seen this, in model organisms to these effects, right? There's the studies and worms. There's been studies in mice. You've got a couple of favorites. I know you like, talk about the mice that got this bun together.
59:27
Oh, yeah, so that one is is bit of a disappointment in the field that we we had these dwarf mice, that Mike Bunkhouse key who was working in my lab. He was the guy that generated the longest-lived mouse. He called it Yoda, and it was very long.
59:41
Live because it had a mutation in the gene for the growth hormone receptor, which means there were small and dwarfs and these little small dwarf, mice would live up to three times longer than a normal Mouse. It was quite an amazing thing and the field was rejoicing. Wow, we've figured out how to make mammals live, that much longer, and then it was noticed that there were shivering, little cold mice, and so the researchers thought, we'll just give them friends. So, you
1:00:06
know what shivering because the lab was called, they were shivering
1:00:09
because they didn't have a companion.
1:00:11
Mice like to live a solitary, but with other mice and so they gave them a buddy. Each of these dwarfs had a buddy and then the majority of the lifespan extension went away when they got there, buddy. Yeah, which is super disappointing. Right? But what it told us was that a large effect of longevity was due to them being
1:00:29
cold. And why is that happening? When we go back to like, thinking about the survival circuit? What's happening?
1:00:35
Yeah. Well, the the trick is, let's go back to the brown fat. What brown fat has a lot of is mitochondria.
1:00:41
Within those mitochondria, they actually quite different. They have high levels of proteins called you, CPS or uncoupling proteins, which insert into the membrane of the mitochondria, and allow those protons that were built up to leak through instead of going through that pump, that makes the energy they leak through. Why is that interesting? Well, first of all that generates heat that helps the animal and we survive cold but also you get fewer free radicals produced when you uncouple mitochondria with these proteins and
1:01:12
Consistent with that. If you make an animal, let's say it's a worm or a fly or even a mouse that has high levels of these UCP genes. They actually live longer. So uncoupling and reducing that free radical load. And you can do this with cold therapy. We think is beneficial to
1:01:29
health and called therapy with people. Collect. Cryo therapy. Is this like short term acute superintendent. You've done this before, right? You did this.
1:01:41
Rogue ninja. Yeah. Yeah, Joe said, let's go do that after the show, which I did. It was pretty chilly. I just had to strip down into my down to my underwear and put gloves on and socks or whatever, but you get to play music. At least, I got to choose Help by the Beatles, which was quite appropriate, Because by the end of those three
1:01:58
minutes you want it
1:01:59
out. Well, the first two minutes. I'm like, what's the problem? This isn't cold. But that last minute. I really thought I was going to get hypothermia and my ears might break off your chattering and she, yeah, you really start to shiver.
1:02:11
Her, which is your body's way of generating Heat by moving your muscles, but it was, it was really enjoyable. I found afterwards. I felt stimulated. I felt lucky to be alive and I felt good for a number of days afterwards, which is probably because my mitochondria were revved up and I was building more Brown fat. That the one thing I think it's worth pausing here to talk about is, why would you do this now? Why don't you wait till you're old to do, cold therapy, and what's been found at least in my says that old mice don't make brown fat, as well as young. My so what you want to do is
1:02:41
Lage. Do these treatments and so that you're ready for old age when it becomes harder,
1:02:46
just like right now we need to be doing vigorous exercise. We can't wait until we're old to do, vigorous exercise.
1:02:52
Yeah, though. It's never too late. We do find that things work in elderly myosin only people. But it doesn't work as well if you start midlife or even
1:02:59
earlier, okay, and maybe that's like the cryotherapy stuff is sort of a can do a vigorous exercise, but you still have to have that low level of perceived adversity just like we have to get like lots and lots of steps in.
1:03:11
We day, but we live in these environments. These temperature controlled environments where it's like 68 to 72. That's not how our ancestors lived at
1:03:20
all. No, we were shivering. Probably, most of the time during the Ice Age. Sure. And our bodies recognize that if we've got those genes that respond and they keep us healthy as we've talked about. So, there are a number of ways you can if you don't have a cryotherapy center near you, what are you do? Well, you can take cold showers, some people do that. I don't I find that unpleasant, but you can do that very cheap to do that or you can do.
1:03:41
Thing that I do actually do, which is sleep with very few covers on my bed and lower down my body temperature and that's also been shown to activate these uncoupling proteins and build Brown fat.
1:03:51
The opposite side of this is heat, which is also something that throughout our evolutionary history. We've had to deal with. We didn't always live in temperature-controlled buildings and we're we've got some emerging research on that as
1:04:04
well, right? Taking a body out of its comfort zone. And so the
1:04:08
all of these things are about taking your body out of his
1:04:10
company. Yeah.
1:04:11
And some of them are really enjoyable. I think Sona bathing is called in, Europe is super enjoyable. And it also is good for your skin. You get to sweat and get get those Paws unclogged. But this is one of the most ancient therapies for longevity. Even before Roman times. They were bathing in these saunas. So the Romans would use fires under the under the floor, but this is something that European still carry on as a tradition, particularly in Finland and other Scandinavian countries where these studies are typically performed on men for some reason. But
1:04:41
Data that I've looked at which will put the show in the show notes, is that there's absolutely no doubt that men who partake in sauna bathing a few times a week often at home because they build this into their houses. Have a dramatic reduction up to 20% in the rate of cardiovascular disease and mortality caused. By heart attacks.
1:05:01
This isn't happening for the same reason as cold therapy work. This has nothing to do with brown fat. There's another thing that's going on here, right? It's
1:05:08
different. In this case. What we think goes on in a sauna is your activated.
1:05:11
Dating hsps. And these heat shock proteins are helping to fold proteins correctly and also stimulate Pathways that are beneficial such as building new blood vessels, making more mitochondria. And one of the reasons that I believe it's true, is that in model organisms, if take a worm, if you turn up his chalk proteins, either by giving them a lot of heat or genetically, modifying them. They also live
1:05:36
longer.
1:05:38
We don't quite know what dosing is right for sauna baths at this point, or like how much how hot the not a ton of research in this area.
1:05:49
No, but it doesn't seem like you can overdo it. I haven't seen any evidence that it's - and I used to before the pandemic. I used to go at least once a week and do multiple bouts of the heat shock in the sauna for about 15 minutes and then jump in an ice bath, which was nearby for 4 minutes and then cycle.
1:06:07
That and I you probably consult your doctor before you do that. I would definitely and I did. But yeah, it can put some stress on the bone, the body, certainly on the heart. But yet the idea though is to shock the body heat, cold, heat cold. And that way you have I think you get the maximum benefit from these adversity
1:06:26
memetics. And again, you don't necessarily need to have access to a sauna to do this. I mean, some people can build them into their home. Some people have them in their gyms. That's kind of a point of privilege. Most people have a bath
1:06:36
or shower.
1:06:37
A hot shower. I certainly do that. I like to turn the heat way up. There are a variety of different Zone has. There's the old-fashioned type, which is the cedar planks sitting in there and you just throw water on Hot Rocks. That's traditional. There are new ones such as infrared, saunas and the infrared light actually penetrates the skin and is thought and there's some evidence real believable evidence that are also in the skin layer can reverse aspects of Aging as well and including improve hair
1:07:04
growth. There is for some obvious.
1:07:07
Reasons. There's a lot of questions. I want to ask about hair growth. We're going to be discussing hair growth, skincare, all these like sort of like cosmetic 8 aspects of Aging things in a future episode, 1 of the commonalities that kind of sensing in all of these things, right? You do vigorous exercise and you get what you know, we term a runner's high and you talked about doing the cryotherapy and you felt like what did you say like blessed to be alive or I've done sweats?
1:07:37
Sweat lodges and you come out of those things and it's just like it's the best drug in the
1:07:41
world. What, what do you think? Why
1:07:45
are these things so similar it is it happens in the
1:07:47
hyperbaric chamber to? Yeah. Yeah, that's one of the nice side effects. That's when you know that you're doing a good longevity protocol because what's happening at the cellular level is those three main defense Pathways get turned on. But at the physiological level, the neurological level you're getting endorphins as well. And that's when, you know, you've actually done the right
1:08:06
thing.
1:08:07
So let's talk about a basic protocol with the caveat that we always make, which is everybody's going to be a little bit different. But if we're trying to get sort of, you know, like exercise cold heat and Hyperbaric. What are what's a good way to do that? We've already talked about the exercise protocol. Actually, I don't think we need to reiterate that. He's you need exercise. Get off your butt right, cold heat and and
1:08:37
Barek. Yeah, well, it as I mentioned I used to do and I will do again, the cycling of the Heat and the cold about five times. During one day of the week. This was on a Sunday with my son Benjamin, but I would say more is better. There's no evidence that you can overdo this. You could even do it everyday. If you don't have access to a gym, you can always use your your house. You can turn down the temperature or you can use your shower and that will work almost as well as dunking yourself into a cold.
1:09:07
Bathtub, or you could do what Gabby Reece and Laird Hamilton do which is shove us into an ice bath with literally with ice in it. I think that you know, you don't need to do that every day.
1:09:17
It didn't you, almost drowned
1:09:19
I did. But that was that was different. That was hyper hypoxia. What they do is they make you do exercise with weights at the bottom of a pool below your height. So you're underwater you have to jump up with those weights to get a breath of air. We're not recommending that at this time. I think everybody should go knock on.
1:09:37
On their front door and do it with them. No, it's but you can get hypoxia from exercise. It's very similar. So we've talked about hot and cold. The Hyperbaric is more of an issue. I think that there's not a lot of these centers around and it's expensive. It's hundreds of dollars per treatment, but that's in the future. I think that that way I wanted to mention that because it's really interesting how it's so similar to exercise and hypoxia at the molecular level, but for most people right now, that's Out Of
1:10:04
Reach, but that's not the only thing in the future. There's a lot of really cool.
1:10:07
All things coming down the path right now, that are going to be a fundamental part of people's lives. Pretty soon. We're going to be talking about a lot of those in upcoming
1:10:16
episodes. We are and it actually I think a lot of people will be excited that we can mimic this adversity with molecules with pills with injections and we're going to talk about that in the next episode in the next episode. Yeah.
1:10:29
So next episode molecules supplements longevity. That's it's going to be a
1:10:33
lot. Yeah. I'm excited about this one because I get questions every day about.
1:10:37
It. And I think it's going to be one of the most downloaded
1:10:40
episodes. Yeah, I think a lot of people are going to want to.
1:10:43
I'm excited to dig in. Yeah. Okay, cool. Thanks for joining us. This episode on exercise and other forms of acute stress. If you're learning from and enjoying this podcast, please subscribe to it on YouTube, Apple podcasts and Spotify on Apple. You have the opportunity to live up to a five star review. If you'd like to support us, please? Check out the sponsors we mentioned at the start. We've partnered with companies, we truly believe.
1:11:07
Vin and they make this show possible. We also have a patreon that's patreon.com forward slash David Sinclair. There you can support the show at any level that you like. Thanks again, and we'll be back next week to discuss supplements and molecules like animation in our Resveratrol and how these impact longevity.
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