Mitochondria, Cell Danger Response, Antioxidant Myths, and More with Ari Whitten

The other chapters are on all the other physiological capacities in the different areas of our body and how they protect us against disease and bolster our health and longevity, but mitochondria, as you said, are also central to this story. This is our bioenergetic reserve capacity.

One of the things that we have to understand is basically any type of stressor you can imagine, any type of stress on that system is creating a bioenergetic stress on that system. Whether it’s toxins, whether it’s sleep deprivation, whether it’s even healthy things like exercise or learning things, like I just described in the brain, and all the sources of bad stress and allostatic load you can imagine, they are all creating an energetic stress on the cells of the body as well.

The capacity of your mitochondria to meet that and handle that energetic stress or not handle it is a huge determinant of whether you will end up with your mitochondria shifted into the cell danger response. Let me give you another data point to overlay on this. It’s been shown in a number of studies that the average 70-year-old has lost 75% of their mitochondrial capacity.

This is a combination of two things. The mitochondria themselves are shrinking, physically shrinking to about half the size, and the number of mitochondria that are present per cell are also being reduced to about half the size. The combination of those two things, if you do the math, since you’re a math guy apparently, better than me, the combination of those two things is a loss of 75% of your mitochondrial capacity.

Now, I hate percentages because it doesn’t really do this justice for people to really get this. What this means is that if you were at 100% capacity when you were 20 and you’re now at 25% of your capacity, this is like going from a Ferrari V8 engine in your cells when you were 20 to a Moped engine in your cells when you’re 25. Do you think that that affects your ability to handle or resist bioenergetic stresses, to resist the forces of stress on that system? Absolutely.

Dr. Jockers: Absolutely.

Ari Whitten: It affects it to a massive, massive degree. This is fundamentally why mitochondrial dysfunction, this buzzword in natural health now is linked with so many different disease processes.

Dr. Jockers: Yes, for sure. I always say the quality of your life is going to come down to the amount of mitochondria and the quality of the mitochondria. Because there’s a big difference between a senescent mitochondria, which all of us have to some degree, and a young, very stress-resilient mitochondria. There’s a night and day difference there. You may have a certain amount of mitochondria, but if a high percentage of those are senescent or age-dysfunctional mitochondria, in a sense, your overall functionality and your stress resilience can be a lot lower than somebody that has the same amount of mitochondria, but a higher percentage of stress-resilient, high-functioning mitochondria.

Ari Whitten: That’s right. I’m glad you brought that up because I left one key point out of the story that I just told, which is, as you just implied, the quality and quantity of the mitochondria in our cells is highly malleable. This picture I just painted of losing 75% of your mitochondrial capacity as you get older is actually just the average of what normally and typically happens to most people. What this isn’t is a claim that “aging does this to our mitochondria in a sort of biologically predetermined way.” Actually, it’s the opposite.

Here’s the good news. Because you’re probably feeling really like this is really bad news, learning that your mitochondria and mitochondrial capacity decline so much with aging. If that’s got you feeling down, here’s the good news. The good news is when we look at 70-year-olds who are lifelong exercisers, they have the same mitochondrial capacity as young people do, so this is not a function of aging per se. This is a function of our lifestyle.

What’s really going on here, in terms of mitochondrial size, mitochondrial quantity, and quality, is that this is fundamentally a product of the way we live and, specifically, the degree of demand we put on those systems. In the same way, I could tell you, and this is much easier for people to understand because it’s much more outwardly visible, as soon as things start going down to a smaller level, humans make the mistake of thinking, “Oh, this is driven by mysterious biochemicals, and I need to take a drug for this,” but when it’s big and outwardly visible, we have a much more time with the logic of understanding things in the proper way.

Muscles. With muscles, if we challenge our muscles by lifting heavy objects, what do they do? They interpret this as a stimulus to adapt to this challenge by growing bigger and stronger. It’s a survival stimulus. Basically, they’re going, in order to better handle the challenges of my environment, to better survive my environment, and to be less damaged by the stress of my environment, I need to adapt to these demands by growing bigger and stronger muscles.

The opposite is also true. Before I get there, this is actually an amazing thing. If you look at a chair or a bicycle or a car or any sort of other object in our environment, any inanimate object, they don’t do this. They don’t have the capacity to sense and adapt to the demands on them. The more demands you place on those systems, the faster they break down and wear out and degenerate.

Humans and living organisms, more broadly, but humans are especially good at this, have an incredible, almost magical ability to sense demands on the different systems of our body and adapt to them not by degenerating but by actually growing stronger. As magical and amazing as that is, there is a downside to it, which is the opposite also is true. What happens if you immobilize muscles in a cast, like if you’ve ever broken a bone?

Dr. Jockers: They atrophy.

Ari Whitten: Exactly. Eight weeks later, you go to the doctor, they saw off your cast, you look down at your arm or leg, and it’s half the size of the other one. Because the body similarly sensed, well, we only care about survival. I guess we don’t need these muscles to survive our environment. They’re not being used, so they’re just an energetic liability. They’re just consuming resources, protein, and energy without serving any purpose that facilitates our survival, so let’s get rid of them.

The same exact principles of growth and atrophy also apply at the microscopic level with our mitochondria. When they are challenged regularly, they grow bigger and stronger, they engage in quality control processes, which is what you were alluding to earlier, mitophagy and preventing senescence, improving the actual health and function of those systems, growing larger and growing more of them from scratch from a process called mitochondrial biogenesis. So you can actually reverse that trend that I was talking about before. You can actually increase the number of mitochondria as well.

If you don’t challenge your mitochondria regularly, and there are physical challenges that challenge the mitochondria in different systems of the body, also, think of it this way, cognitive challenges also challenge the mitochondria of the brain, of the neural circuitry of the brain in unique ways, and there can even be broken down further from there of specific types of cognitive challenge, challenge the mitochondria in different systems of the brain in unique ways.

In response to those challenges, those mitochondria adapt by growing bigger and stronger and becoming more numerous. The converse is also true. If you live a life lacking in those stimuli, in those challenges to those systems, the mitochondria shrink and atrophy and literally die off, so you have fewer of them. As a result of that, you massively decrease your physiological resilience.

Dr. Jockers: You’re talking about this concept of hormetic stressors, like exercise, for example. If you do an intense workout like I did today, like you probably did today, if I took my blood work right while I was doing that, or right afterwards, it would look like I had a heart attack, massive inflammatory numbers, but 24 hours later, my inflammatory numbers are really low, I show all signs of great metabolic health, and my system has adapted to create more endogenous antioxidant production, better oxidative stress buffering, and just better cell-to-cell communication, all the things that we want for stress resilience, but I got the right dose.

That’s the other thing with the hormetic stressors because there’s certainly a limit where you or I could easily overtrain, I’ve been there before, where we’re doing too much physical activity, not resting enough, not getting enough of the stimuli, like melatonin and human growth hormone production from good quality sleep, to where we’re not able to adapt and recover effectively, and then we’re overstressing our system.

We’ve got to get the right dose of these stressors, like exercise, like learning, which anybody that’s a little bit older, you start trying to learn something new, you get pretty easily frustrated, so it is a stressor on the mind. We’ve got to get the right dose of these hormetic stressors to appropriately boost our resilience factor, and not too much but also not too little.

Ari Whitten: Yes, that’s right. There’s a number of principles to extend off of that, but one thing to understand is that basically too much– let me put it this way. We have an abnormal way of thinking about certain stressors. Exercise, which we all think of as something that promotes health, is, as you alluded to with your blood test results there, a stressor on the body. It is a physiological stressor that creates metabolic waste, that creates a big spike of oxidative stress and even inflammation in the system.

It is, genuinely, a stress on the system. If you overdo it, as you’ve said, if you overwhelm the system with that stress, it will create harm. The beautiful thing though is that when we engage in types of stress that are biologically appropriate for us because they were historically present in our ancestors over countless millennia, what happens is we are uniquely well adapted to creating adaptations to that stressor that actually make us stronger.

This is a distinction between certain types of stressors that are biologically appropriate and were present for the human species for a very long time, that we are accustomed to versus certain types of stressors like, let’s say, lots of the modern toxins in our environment that we are not well suited to adapt to that we have enormous difficulty transforming from something bad into something good.

Exercise is a stress that we can transform from something that is, in the immediate terms, something bad or potentially bad, into something over time when we engage in it consistently and when we engage in it at a dose, as you said, that is appropriate for our individual capacity, which differs widely between individuals. When we get that dose right, and we go just a bit outside of our comfort zone, just slightly above our current capacity, we stimulate transient harm, basically, but that transient harm is transformed into signals that make adaptations that in the long term make us stronger, healthier, and more resilient to future exposures to stress.

Dr. Jockers: Yes, absolutely. That’s this idea of hormetic stressors. There’s a whole number of different hormetic stressors, exercise being probably the number one example that people understand, but learning, like you mentioned, that’s a hormetic stressor. In our society today, a lot of people are doing things like cold plunges, getting cold exposure. There could be certain types of breathing like breath holds or just box breathing and things like that that are somewhat of a hormetic stressor as well because we’re being exposed to more carbon dioxide. So many people are short shallow breathers, and I know you have a whole training on that.

Fasting is definitely a hormetic stressor. Our ancestors would go, because they didn’t have pantries, so they would go, at times, long periods of time without consuming food, and their body was able to adapt to it. Time-restricted feeding or a fasting strategy, that can be a hormetic stressor that, if done in the right dose, can make us more metabolically fit and stronger. Might obviously help increase the quality and quantity of mitochondria. We have all these types of hormetic stressors that can help prime us for resilience. Where do you recommend people start with some of these different areas that they can focus on?

Ari Whitten: Yes, there’s so many. You mentioned a good list there. I would add sauna exposure to that list.

Dr. Jockers: Heat, yes.

Ari Whitten: Another aspect is actually phytochemicals, very common. An extremely widespread misunderstanding is that most of the beneficial phytochemicals are actually not antioxidants, as most people think they are. They’re actually xeno hormetic stressors or xeno [unintelligible 00:41:51] and they stimulate a low-level oxidative stress that is transformed, much like exercise and many of the other stressors, transformed into beneficial adaptations.

The spike in oxidative stress is actually transformed into an adaptation of bolstering and building up what’s called the ARE, the antioxidant response element, which is our internal cellular antioxidant system. The more you engage in these types of stressors and really exercise, breath holding, sauna exposure, cold exposure, all of these actually create oxidative stress, which is something that we all have been taught in most circles to think of as a bad thing, but actually, interestingly enough– well, I’ll tell an interesting background story related to that.

About 15 or 20 years ago or so, researchers actually decided to study this. What they did was they recognized that exercise had a whole bunch of health benefits associated with it. At that time, of course, it was already known that exercise was very good for us, that it helped to prevent disease and so on, but it was thought at that time that it’s really unfortunate that exercise also creates this big spike of oxidative stress of free radicals, and that these free radicals are damaging us. So what if we take antioxidant supplements in tandem with exercise, so we get all the good stuff from exercise, all these benefits, reduce risk of so many different diseases, but we eliminate the downside of exercise, which is these free radicals, this oxidative stress?

These researchers found something unexpected in these studies. The more that they supplemented with antioxidants, vitamin A, C, E, things like that, before, during, or after exercise, the more that they actually reduced and canceled out and inhibited the metabolic benefits of exercise. Because it turns out that part of the adaptations to exercise, a big part, are actually adaptations to the oxidative stress induced by exercise.

That oxidative stress is actually a signal to grow that internal antioxidation system, redox system, bigger and stronger. If you take exogenous antioxidants that reduce the oxidative stress, you reduce the signal on your internal antioxidant system to grow stronger, and it turns out the oxidants are actually a vital signaling molecule for mitochondria themselves to detect that there is a need for increased bioenergetic capacity.

All that stuff I was talking about before, about mitochondrial growth and biogenesis, actually depends on oxidative stress signaling. Mitochondria have to detect the presence of oxidative stress, which is essentially a signal that is translated by them as, oh, we’re being overwhelmed. This stressor is exceeding our bioenergetic production capacity, so let’s adapt to it to prevent oxidative damage from future exposures to the stress by growing bigger and stronger so we can produce more energy so we can handle this bioenergetic demand on the system in the future.

Those are all wonderful elements. There’s a number of psychological aspects to this story as well. We create psychological adaptations to mentally difficult things in the same way that we create, in the psychological as well as neurological, actually at the level of the brain in very much the same way that we create physical adaptations and cellular and biochemical adaptations to more physical stressors. Cognitive reserve capacity being one of them, but there’s actually many other dimensions of that as well.

The actual resilience to stress is a neurally mediated, in large part, capacity like, what is your psycho-emotional reserve capacity? What is your level of resilience to handle psychological and emotional stress? Courage, willpower, these are also neurally mediated capacities that are trainable in much the same way that muscular strength is trainable via lifting weights.

Dr. Jockers: This is really good stuff. We can go for another hour on this, but what I will say is that I know the listeners got a ton of value out of this interview here. Guys, you can check out Ari and all his podcasts, his programs, his supplement formulas at the the energyblueprint.com. I know he’s got a great program on breathing, also one on gut health. He’s got a great book as well, a couple of great books. Eat for Energy: How to Beat Fatigue, Supercharge Your Mitochondria, and Unlock All-Day Energy talks about the phytochemicals, talks about time-restricted feeding, a lot of the things that we discussed here just recently.

He also has the ultimate guide to red light therapy as well. Some great books. Ari’s one of my favorite people in the natural health space to talk to about these ideas. I hope you guys got a lot of value out of this. Ari, any last words or inspiration here for our audience?

Ari Whitten: I would say the big principle that I want people to realize that really is an extension of everything that I’ve talked about here is to realize how much of your physiology is malleable and plastic and is a function of your behaviors, and you are not, as so much of the medical narrative wants to push on you, just a victim of biochemicals floating around in your body. The biochemistry that you assess on blood tests is hugely a function of the structure and function that you have built, that you have built in different systems of your body. The biggest key to health and disease prevention and energy and longevity is building those capacities.

Dr. Jockers: Love that. Ari, always a pleasure, my friend. Be blessed.