interview with dan pardi...interview with dan pardi i'm dan pardi. i do sleep research, and i...

Interview with Dan Pardi

I'm Dan Pardi. I do sleep research, and I am also very interested in the question of how do we be healthy and all the different ways that we can understand what that looks like and how to implement it in our lives right now.

I think there's a lot of theories about what makes us healthy and live long, and I think it's always important to look at the examples of the world where that's actually a reality and whether or not we want to implement what they do in these different zones prescriptively is another question, but I think understanding those populations as well as possible is a really smart thing to have at our disposal.

It's such a good question, and I don't really have the answer in my mind, at least in terms of I like the idea of have strong opinions and hold them loosely, but can we just reproduce what they're doing and expect the same result? We live in a very different world. I think what we can do now is we can test and see how we feel, and that sometimes can be misleading and sometimes it can be really informative. We're trying to read the tea leaves, and it's understanding what's known in the world, understanding ourselves better, understanding ourselves now and then having things that we want to test and try to see does this meaningfully augment my day-by-day experience? Do I feel better? Do I think better? I think having a very tight relationship with how you think and perform is one of the smartest things we can do.

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We are products of our environment in so many ways, and the world in modern life is different than it's ever been in all of human history. Not only that. If you're born this year, life is different than it was 10 years ago, and that trajectory is not going to change. It's going to accelerate. We're born into a world that is really different than what our biology expects. We have the ability to live at all different parts of the world within a lifetime.

We have modern forces that are shaping what we do and what we should be aspiring and driving towards, and so a lot of people aren't thinking necessarily about their health every day as much as people that are more geeked on the subject, and so they are really subject to the pressures of their job, pressures of their family and then ways that we can manipulate interests and behavior to use and app a lot, to spend less time with people and more time inside, to seek conveniences so in the limited amount of time we have, we get more personal time. There's a lot of things that shape how we live, and we definitely need ways to take charge of that so that how we are living is not entirely affected by those pressures, those modern pressures and forces.

There are many organizations, companies, VCs investing in technologies, the point of which is to entirely take control of how the person is living. We're going to tell you what to eat, when, when to go to sleep. That I think is the misappropriation of potentially useful technology. Technology is better when it helps us become more in touch with ourselves, not less in touch. I don't think that we need something that always is telling us this is how you live right now. I do understand that there are probably use cases where that might be useful. It can get people better, but I think we should ... We have this relationship with ourselves. We should aim to understand ourselves better in the world.

What is health? It's proper biological functioning. That's how I think of it, a good general description. What the World Health Organization says health is the ability to withstand insults and challenges and maintain homeostasis or an internal balance, but I think probably one of the most important aspects of health is their second aspect of their definition, which is health as an attribute to helping you realize your aspirations and to live a high-quality life. We know that delayed reward or delayed ... yeah, sorry. What's the word I'm looking for? We know that delayed discounting is something where if you don't eat this cheeseburger now, then how much health benefit will you


get in the future? That tends to be intangible, and it's not a very powerful motivator.

While most people are ... recognize that they don't want a chronic disease, we don't do anything healthy usually so that you prevent peripheral arterial disease, right? You do it because of culture, and it feels good, and you do have a recognition that it's good for the body. I think one of the best ways to implement health in your life, to be healthy, to do those things that are hard or at least different than what everybody else is doing is to focus on performance. Am I thinking well? Am I going to perform well in my life, in my social relationships, in the things that I care about. My performing well at a meeting tomorrow in a presentation. I think if you can harness that understanding and potential, then it can really fuel your ability to do the right things or things you want to do to be healthy. It is a tighter feedback loop and that we know from a behavioral perspective that that really does matter.

On one hand, technology can completely distract us from our health. It can lead us astray. You could spend all your time engaged in theoretical health behaviors of testing and diagnosis and reading without a lot of doing. I have this saying that knowledge itself does not immunize you from living a healthy lifestyle. Right. You could have theoretically the most knowledgeable professor on a certain topic, and they are not protected by their knowledge if they don't implement that into their lives. Conversely, you could have this teenager that has a very natural lifestyle, is out waking up early and surfing and eats good food in their family and has low social stress in a good community. They might not know any of the theory or benefits of why the things that they're doing are good, and they're going to get all the benefits from it.

I do think that knowledge matters because in our world, again, as we were talking about earlier, our behaviors are often shaped by what's convenient and what is everybody else doing, so knowledge on something can help us make choices that are different than what everybody else is doing around you. I think that to a degree, having fluency around certain subjects can help, and I think technology can facilitate that. I also think having more knowledge about yourself can potentially be useful, but it can also potentially lead you down some rabbit holes that aren't that helpful.


Right now, we see that with things like Fitbit. You see reports that some people are trying to do it for weight loss, and it actually made them gain more weight. There is again potential for these things to be useful, but you have to understand how to use them, that it's not a silver bullet. It's a part of more of a whole ecology of health behaviors that we need to engage with, and if it is again reinforcing a lifestyle pattern, that itself is good, then I think technology can help us live more naturally. When it helps us live more like a technocrat and disconnected from our natural behaviors, then I think we get into trouble.

For a long time, I've been compelled by the idea of ancestral patterns of living, and I think that some people put all of the answers into trying to replicate and understand what do hunters, gathers, modern day or ancestral estimates tell us about how much potassium we should be getting, what's our movement patterns like. I think is another valuable, informative source, so we combined ancestral understanding; we combined modern-day science; and we combined an understanding of behavioral science and then technology to facilitate all that.

I think we have a nice ecosystem in the realities of modern life to help us say, "Okay, I'm going to try to live more naturally, and what does that mean? It means that you're not over-indexing one behavior.you're not trying to say, "All of my health efforts are going to go toward exercising more." It's a linear ... The more I exercise, the healthier I get. But rather that there's a lot of different factors. There's sleep; there's food; there's stress both dealing with handling psychological stress and also seeking out stressors so that we have different exposures. Exposure to the sun, exposure to cold and hot. Those are all stressors, but those actually will facilitate our important biochemical signals that are a part of our health.

We sometimes think that we're perfectly healthy as these free-standing units, and the reality is that our health is in relation to the environment around us, so the exposures and how we live. That means that we probably instead of trying to just run more miles per week, that we want to just get more of a variety of exposure types. I think that ancestral patterns can provide a nice template to say there's a heuristic, like what do they do? How can that guide me in the type of behavior now? A good example would be do I want to just get up in the morning, run a couple of miles, and then sit at my desk all day in a low-lit room at a computer? Probably not.


On the other hand, do I want to get some morning light exposure? Do I want to be up and have different types of movement throughout the day, so more low-intensity exposure, more high intensity? Do I want to also rest and nap? That can all be informed by thinking, "How do our ancestors live?" Then using that as a guide to try to help us do better across more of those domains. I think that that's some really informative heuristics.

Yeah, so if you look at equatorial regions, the band of temperature that they experienced across a year was somewhere between maybe 50 degrees to 90 and then sometimes beyond that, depending on where you live. That is actually a relatively narrow band for what a lot of people are exposed to, but we have a way to use institutionalized shielding, so we control our environments when we're inside a room. We control our environments when we're outside by putting on multiple layers of clothes. That all adds to more comfort, less stress.

What happens though is then the body becomes less comfortable in different heat ranges. We have a harder time controlling with heat, although you can have air conditioning when it's really hot, but it's a lot easier to manage cold. Now why is that potentially important? Well, if that was over millennia, the natural exposures that humans got, then there might be, there might be important signals that are derived from those types of exposures.

There might be benefits to specific exposures in temperature, particularly cold and also hot, that facilitate something important in our health ecosystem of our body. For example, we do know cold exposures will trigger something called heat shock proteins and also cold shock proteins. What these do, these are chaperone proteins that will help to prevent protein aggregates. We know Alzheimer's disease built up a protein aggregate called beta amyloid. We also know that they will add to stress resistance, so the old idea that don't go outside when it's cold, and you're going to catch a cold, that's probably true if you don't get cold exposure often, but if you do get cold exposure often, then you're actually building resistance. You're building resilience.


That's a part of our health is to build resilience, so a great example is sunshine on your skin. If you have not been getting much sunshine over the winter, and you step outside, and you want to let's say get a tan, don't go spend seven hours in the sun. You're going to burn, but if you get a little bit of exposure, that stress, that hormetic stress will cause an adaptive response causing melanin to produce a dark pigment in your skin, which makes you more resistant to more sun exposure, and you build your resistance. We can do that with cold. We can do that with heat as well. We do it with exercise. Adding stressors into our life is actually an important part of our health. It is that stress that facilitates and adaptive response. That adaptive response ends up being health promoting and keeping our body functioning as we want it to.

How can you add more cold to your environment and to your life, and how do you do that? Well, and easy way to do that is to take a cold shower in the morning. I think that there's additional benefit of having a strong sympathetic response from that cold exposure, which will then help with circadian alignment, so you have better circadian rhythm alignment. If you think about what are circadian rhythms, I'll introduce that. These are repeatable, 24-hour processes that help keep our body in rhythm.

We know that there are certain times of day where we have what are called phase relationships where one hormone might be high, another one is low, and that's going to then create almost like a lock and a key in terms of the cellular response that's being instigated. There are different activities that the body does at different times of day that are, again, part of our health process.

Yeah, so circadian rhythms are a really fundamental part to our health. Only in the last 10 or 15 years have an understanding of circadian rhythm that's now been derived by science, has it become a part of the equation of our health. Same with gut microbiota, same with epigenetics. Before that, it was diet and exercise, right? Now we know that there's these other things that are really fundamental that are at play, and so what circadian rhythms do is they help to look at past behavior to then try to predict a physiologic response for that time of day. That's why we don't want ... The body doesn't try to have you get up seven times during the night while you're sleeping to go to the bathroom.


You feel hungry during the day. You feel like going to the bathroom during the day, and at night, there's a whole other set of physiological activities that take place that are suited for that time of day. Now, when we have light exposure, which is the main synchronizer of circadian rhythms at times when your body usually would be getting darkness, so having artificial light at night, that's going to tell the brain that it is daytime. It's going to act naturally to that signal, which is then going to create an unnatural or potentially pathogenic response in the body. Another signal there is getting cold exposure early in the morning, and so you have this robust catecholamine response from epinephrine, and that is going to make you feel more alert.

It's going to help to align your circadian rhythms, so it's going to contribute to that panoply of signals that helps your body understand this is daytime, and that's going to keep a lot of your rhythms in line. Let me stress the importance of this. We know that people who do shift work or that have chronically misaligned circadian rhythms, they have fourfold increases in cancer rates. They have multifold increases in cardiovascular disease and risk. It is a clear indication that the body is not functioning as it should because it doesn't understand what time it should be doing things, and so you have this misalignment that is affecting our health and our performance. We know that it impacts memory. We know it impacts cognitive functioning and physiological processes too.

That's one thing that's talked about less is the cold exposure-induced catecholamine response, but that's one thing that I've noticed that helps me have more robust alertness during the day, which then actually will facilitate deeper sleep at night.

Circadian rhythms are again trying to anticipate what the needs are of the body based off of past experiences and exposures so that, for example, if you typically eat at every morning at 8 a.m., the body is going to prepare enzymes that are going to help to process that meal. If you are eating a certain type of food every single day at that time of day, those enzymes are going to be suited for breaking down that type of food at that time of day. In a recent podcast of mine, we talked about breakfast skipping, and I think if you have high variability in your meal times, that is a condition that is less favored for proper metabolic responsiveness to the meals that you take in, which could lead to poor regulation of blood glucose and could also lead to things like obesity.


That's one indication and an example. Now does that always mean that breakfast skipping is a bad thing? Actually, I don't know because maybe if you always skip breakfast, and your first meal is let's say at noon, that could be favorable. There's more research that needs to be done to understand these things more closely, but another good example is just for example how blood glucose is regulated at night.

When the body releases melatonin, which it does in response to something called dim light melatonin onset, which means that the certain tone and intensity of light is coming into the eye, it's affecting something called intrinsically photosensitive retinal ganglion cells, which are types of photosensitive cells in the retina that will communicate not to the primary visual cortex, but back to an area of the brain called the master clock. That master clock then is then saying okay this is the time of day that it is, therefore, initiate these programs. Again, how does the body maintain stable blood glucose levels over the course of the night? Well, one thing that dim light does it stimulates melatonin.

Melatonin will directly affect pancreatic beta cells to suppress insulin release. Insulin, as we know, will store glucose, right? If you're suppressing insulin, it's going to actually help to keep blood glucose available in your bloodstream for longer, right? You're going over a seven-hour fast. Now, that's not the only thing that happens. You also see a buffering of blood glucose by a growth hormone response in response to slow-wave sleep. That will also will cause insulin insensitivity, which typically is thought of being a bad thing, but it's actually an adaptive physiological response to maintain blood glucose. Then during the night, it changes, so as you go through your slow-wave sleep and then into more REM sleep, you see towards the end of the night more cortisol being released.

That then helps to then produce more gluconeogenesis in the liver and also to release some glucose from your cells. Altogether, you have different mechanisms, all circadian controlled, that then help keep stable blood glucose levels while you're fasting. That's a really nice explanation to see how this orchestration of your physiology is all being timed so that you end up having good, stable energy levels, and you're not waking up in the middle of the night because you're starving or because something is alerting to you because of poor bioenergetics. That's a nice example then.


Biomarkers are theoretically these things that we can rely upon that indicate current or future health. If you get, for example, a measurement of inflammatory marker, that can tell you that there's something going on or that you're healthy. A lot of the establishment of our biomarker ranges were within a context that has already shifted greatly from a more ancestral natural living condition. How much we can rely upon those markers, all of them, is variable. Some of them are more productive, and I think we're going to learn a lot as we enter into the space of big data, where we're able to collect a lot more data on a lot more people and also during what we'll consider more natural healthy times versus just trying to predict a disease or you may already have it.

You have already had a heart attack, and so now we're actually trying to prevent the second one, and we're going to measure these certain markers. Do I think that we're going to enter into a period where we're going to be able to collect a lot of data on ourselves? People are going to be making decisions off of that data that is going to lead them down some wrong paths potentially, but through it all and through a period of sort of awkward teenage years of big data, eventually, we're going to arrive at a place where we understand populations and subpopulations and perhaps even some things that are uniform for all humans that are predictive and indicative of health. I have higher confidence that if we manage two of those markers will indeed will be driving towards health, will help an individual get towards health. That's I think the reality of the situation. How soon we'll get there, I don't know.

We know that we live in a much more sterile environment than we have in the past, and children that grew up with dogs and grew up on farms, they have more diverse ecology in their microbiota. That seems to correlate with future health outcomes, positive ones. Less cardiovascular disease, less cancer. We also know that for example children that are born in the ICU, the NICU, so if they're born prematurely, what did they use to do? They would keep them under 24-hour light exposure because the nurses will want to monitor the health of the child. Well, it turns out that their circadian system doesn't fully develop until for six months after the child is born, so they're getting circadian cues from their environment and also from the mother.


If the mother is up late at night reading a book or gets up to feed the child late at night and turns on a light and that alters their circadian rhythm, those signals are being passed to the child and that's having an influence on the child's future for the rest of their lives because it's affecting the health of the circadian development. Excuse me, it's affecting the development of the health of the circadian system. Those are some interesting exposures, but we also know that who we're surrounded by, life purpose, there's a lot of things that can lead to subconscious psychological stress, whether you're aware of it or not.

One very interesting thing about people is that we will acclimate to our stressors in our lives. If things are improving, and it takes eight weeks for them to improve, it can be meaningful but invisible. The same meaningful but invisible trajectory can happen in the other direction where you're performing better at one point, things have gotten worse over eight weeks, and you don't see it. You don't really see it. We don't have that objective feedback that's constantly telling us. Sometimes you can. It's not unseeable, but it's easy to overlook, and how do we address that? I think, again, really understanding ourselves and checking in and yeah, are there some things some objective measures perhaps that you can ... a battery of life health and quality of life?

Those things are all I do believe in the power for objective technological measurements to inform us and help us have that ah-ha moment. Ah, there is something here. But I think that subjectively just having that really good relationship and taking a moment for some metacognitive processes of saying stepping back and then thinking about your life, like how am I doing? How do I feel? How are my behaviors aligned with my goals for how I want to be living? All of that really matters, and so yes, I'm super excited about technology. I think that eventually it'll help us in our own efforts, but we have a lot of power right now, and I don't think we should be looking for one silver bullet that's going to explain everything or waiting for the future to have all of our problems solved.

We don't know what's going to actually happen, and we have a lot of information right now that resides within you, but the problem with listening to yourself is that we have confirmation bias. We can see things that aren't there, so just try to be very accurate with what you see. Hold your opinions loosely, and realize that you might be doing something right now that you think is good for you, and it might not be. Be open to modifying


your approach to find something better if it's not serving you as much as you think it is.

So many aspects of our health and how we live are dependent on one another, so the food we eat will impact the sleep we get at night. The sleep we get at night will impact our desire to be physically active the next day. The physical activity types, modes, and modalities that we actually engage in will affect what we choose to eat and how we sleep, so they're all interconnected. We think of them in silos, but the reality is is that ... and that's okay to try to understand individual contributors with better fidelity, but ultimately, they're all interrelated, and so we have 24 hours to affect how we're living, the exposures that we're under, the behaviors that we engage in.

That is our template, right? That's what we have to work with, so all the knowledge that you have, all the technology needs to be coalescing in this period of a day to guide to then hopefully have you have these right types of exposures and to including exposures to friends and including exposures to the right microbes and foods. Now we do know that light during the day have a very important impact on light at night ... or excuse me sleep at night. Part of that is hormonal signaling. Part of it the entrainment or the anchoring of our circadian rhythm. Let's say you get eight hours of sleep, and you typically sleep from midnight to eight.

That's your usual pattern, and one night you go to bed and you go to bed at 4 a.m., and you wake up at noon. Eight hours of sleep, right? That sleep will not be as restorative, and the reason why is because your body ... sleep itself is a circadian rhythm, and your body is used to getting slow-wave sleep at a certain time and REM sleep at a certain time. Consistency of schedule in general is a valuable thing. Now we also know examples where cultures will stay up way past their typical bedtime and dance late in the evening, and that's one thing that I've always noticed is that dancing was a big part of ancestral communities.

It was a way to bond. It was a way to be physically active, and so this concept of orthorexia is an important one, which is I do think we need to be mindful and drive the right behaviors against this backdrop of common lifestyle patterns that we know lead predictably to disease. At the same time, we have to have the ability to just embrace the opportunity to go out late one night with friends and live life in that regard as well. That's the art of healthful


living is balancing between trying to have your average patterns be healthy at least the best in terms of what you think is healthy and driving towards that as best you can.

Then being able to step away from those, that pattern, and not have it be such a psychological stress that it doubly impacts the negative health stimulus. I think that's a really important thing for people to keep in mind.

On one hand, being healthy really means that you have to say no to things that are pleasurable. You can't just eat donuts and ice cream all day long, at least from what we know about our health now, that doesn't seem to be health promoting. We know that we need to make time for exercise and physical activity in our lives. We need to make time for these things that that standard pattern doesn't facilitate, but at the same time, there are opportunities that come spontaneously in life that means that you're going to get off of your pattern. It could be an incredible meal, and it could be a late night at a symphony or a dance party or whatever is motivating and exciting for you.

I think in an ideal scenario is that your average pattern is defined by what you consider to be this healthy pattern. That defines your pattern of living, and yet when you deviate from that, you have one, the ability to deviate from that, and when you do, it is not a huge stress to you psychologically that you embrace it; you make the most out of it; and you consider part of that of a good fulfilled life and know that if you're going to say yes to it, which you should at times, that that healthy attitude is going be probably as big of a contributor to your health than that same efforts applied to doing it right most of the time.

What you eat in a microbiotic community is going to have an impact on your sleep. Things like lactobacillus rhamnosus and L. reuteri, they have shown that it can actually have an effect on the brain, and it can actually cause relaxation and less anxiety, which can then facilitate better deeper sleep. There are 50 to 70 million people in the United States that have chronic sleep issues. Most of the majority, the vast majority are insomnia and obstructive sleep apnea. Insomnia, there's many different types, but primarily it's an anxiety disorder, meaning that you have for one reason or another a hard time shutting off your brain and then that creates more anxiety as you are trying to sleep, and you're unable to.


That then creates this ... Most people will experience this where four or five bad nights in a row leads to more anxiety, making it harder to sleep, and you have to break that cycle. The gut microbiota, we now at least understand that there's an association between both probably the development of the central nervous system and its tone. Then throughout life, if there are significant changes either through heavy antibiotic exposure or other stressors, that we could end up in a situation where those signals lead to heightened reactivity or responsivity of that central nervous system or anxiety. You become more anxious.

Both a physiological signal can trigger sensitivity of the central nervous system, and then the psychological understanding of how you react to that, that stress, can also exacerbate it or can improve it. We want to have control over the things that are controllable with stress. Do you have an ability to calm your mind when you notice that you're stressed? That skill or ability is an important one. That's one thing, but then we also ... It's good to understand what are those physiological signals that make us more stressed, and so we have an understanding that there is a connection, but I think how prescriptive is that understanding currently?

I think like with everything else in the microbiota, we can try things, but what we know in one phenotype in one person, like here are people that sleep long and this is the composition of their gut microbiota, that might not be prescriptive or predictive if you try to then shape another person's microbiota to look identical to this group. They might actually experience no benefit at all, possibly a benefit, or even a worsening of their sleep or a lessening of their sleep. Typically, when we look at sleep, we look at total sleep time. We look at sleep efficiency. We look at the depth of different stages.

Are people getting an adequate amount of slow-wave sleep and REM sleep? What is the concatenation of those stages? That's just from PSG or polysomnography, but that is sort of a gross measure. We know that there are other detectable things when you use more sophisticated measurements like FMRI, etc., to then see, for example, are sleep spindles happening at the exact moment in time when you're getting slow-wave sleep? If so, you're much more likely to have an improved memory the next day than if you had the same amount of slow-wave sleep and sleep spindles, but they were


misaligned. We see that when people age. Yes, the microbiota I would say undoubtedly is important for the health of the human and therefore the health of sleep. How exactly do we want to try and manipulate it? What do we actually do? We're then trying to facilitate that healthy colony.

We tend to think about nutrients when we're thinking about food. We tend to think of nutrients and calories, right? How many calories are we getting, and what are the types of nutrients in the food? But another big very important area is chrononutrition. We talked about circadian rhythms. A part of that is when we're taking in our calories. Then you can look at what is the composition of those calories at that time of day. There's indication now that a shortened eating window, so having a long overnight fast of at least 13 hours associates with better outcomes in people that have breast cancer and less incidents of breast cancer. That probably translates to other types of cancers as well. That's just where we have the strongest signal at the moment.

Then there's the question of well, do we skip breakfast? Actually, a lot of the science shows that if you do skip breakfast, you have a poorer second and third meal effect. We don't metabolize the next couple of meals as well as if we did eat breakfast. But it's such a complex subject, so I wd say overall right now, the indication is that eating more of our calories earlier in the day seems to be better, but that's against the backdrop of what is reality. The reality is is that you have more control over the food that you take in the morning I would say. I would say breakfast tends to be more of an independent act.

Dinner is with more family. It's more with friends. It's more social, and so what I think is a good heuristic now is where do you have greater control over the variability of your diet. For me, that means that I have more control over breakfast. I'm still interested in exploring eating breakfast late but doing so at the exact same time every day. I don't want to be eating breakfast at 8 a.m. one day and then noon the next day and then 8am the next day. I think that that creates a problem. The body again is trying to predict appropriate physiological responses based off of previous exposures.


One thing that we want is a long enough window to allow for certain processes to take place that might be cancer suppressing. Next, we want to then have good reliability of meal timing, and then lastly, we probably want to be eating our last meal no later than three hours before you when you go to bed. Why? Well, one signal for deep sleep is the hormone ghrelin. Ghrelin is an auxetic peptide, so it's released from the gut lining, and it is the only gut-derived peptide that actually will make you hungry. The rest of the gut peptides are usually released in response to a meal. Cholecystokinin, PPY, GLP-1. These actually suppress appetite in response to taking in food.

Ghrelin is an episodic hormone that will rise and fall across the day, so after you eat a meal, ghrelin is low. Several hours after that meal, ghrelin levels will rise again, and that will stimulate hunger and energy deposition. It also is involved with reward mechanism and sleep promotion. In fact, before it was named ghrelin, it was called a growth hormone secretagogue. That was its original acronym. We know that it's probably very important in some of the metabolic processes like fatty acid synthase, a prostaglandin E2 synthesis that all of them are involved in the generation of sleep initiation, and so when we eat late, late at night, we disrupt that metabolic signaling.

We suppress those hormones. We suppress the pathways that those hormones will trigger, and as a result, we might get lighter, more disrupted, less healthy sleep, less restorative sleep.

I get the question a lot of what's most important, sleep or physical activity or diet. The way that I look at it is imagine a three-legged stool. What leg is most important? If each one of those components are a fundamental part of healthy physiological functioning, which they are, then an individual might have greater need to address poor sleep or more physical activity or better diet. But from a physiological perspective, none of them are more important than the other. We have requirements around each of those domains and others, and we need to try to meet those requirements as best we can.

The question of what is the purpose of sleep has been a fairly difficult one to pin down. Is there a solitary purpose of sleep or do multiple things take place during the sleep phase that are important for healthy functioning? I think that that's probably more the reality. We do know of recent data starting back with a science paper in 2013 that when we go into slow-wave sleep, there is a very important process that takes place where our


glymphatic system, so the brain doesn't have a lymphatic, but it has this glymphatic system. The space between neurons will increase by about 60%, and during that time, amyloid proteins, which accumulate in response to energy usage, they are produced in response to just thinking and having a more active brain during the day than you have at night.

Because of the energy expenditure, you're more likely to produce these protein aggregates. Now that's a normal part of physiological functioning, but if you're not purging those potentially neurotoxic plaques at night, you have an accumulation of them and that can absolutely lead to mental impairment and cognitive impairments, including the biggest one, which is Alzheimer's disease. The connection between poor sleep and Alzheimer's disease is very strong. Now that typically happens during slow-wave sleep, so there's two different types of sleep. There's REM and non-REM. In non-REM, you have light and slow-wave sleep.

Slow-wave sleep, you have a release of growth hormone. You have this again purging of these neurotoxic substances. Another thing that takes place then of course is ... That's one thing. It's the purge the use-generated substances. That's good. We also know that as we are thinking during the day, we are using energy, and one marker of that energy usage is a substance called adenosine. Now when we have high levels of adenosine, it makes us sleepy, so a great way to understand that is the most adenosine antagonist or blocker of adenosine is caffeine. Probably know somebody that drinks a cup or two.

It's a part or modern life, right? We're a little groggy in the morning. We have a cup of coffee. The coffee blocks the adenosine receptor, and adenosine can't promote that sleepiness signal. But adenosine at night has a very important role. It'll trigger different immune substances like TNF-Alpha and neuroleukins. Those will facilitate the sleep initiation, sleep dep process and also will facilitate neuroplasticity. Neuroplasticity is our body's ability to have exposures during the day and help us adapt or acclimate to what's happening in your life specifically. It's the ability to neurons to connect with one another, disconnect, and connect to another neuron.


That needs a certain environment, and that environment is then facilitated by daytime usage, followed by an immune response at night, and that immune response then will help us with memory formation, so memory and learning are oftentimes uses synonymously, although they're a bit different, but that is a very important thing that takes place over the lifetime. Think about how you are different than you were 10 years ago and 20 years ago and how the experiences you had then to now have led to the crystallization of different sort of intelligence in you, has led to a different perspective and belief.

That is all your ability, the brain's ability to take in new information, make adaptations to it, and that is facilitated by sleep. If we didn't have sleep, then we wouldn't have that stable environment for plasticity to take place.

The connection between sleep and physical activity originally was presumed to be a strong one. Early investigations into that connection were you could say disappointing or at least in the strength of the connection was not easily observed. My friend Matt Buman, he's a professor at Arizona State University, we've done collaboration together. A lot of his work has looked into the connection, this bidirectional connection between physical activity during the day and then depth of sleep at night, and there is this connection. When you sleep better, you're more likely to be physically active the next day, and when you're physically active the next day, you're more likely to have better sleep at night.

Where does that connection occur? Well, we know if people are subject to bedrest, so they have a broken femur or even if it's an experimental research studies where they put people in bed, that will cause fragmentation of their sleep, a lightening of their sleep. You actually start to see those people sleep more like an older adult, right? Where they don't have as tight consolidation of their sleep in an eight-hour window, but rather they're up a lot at night and then they sleep and nap more during the day. You also see this, it's almost like an asynchronization versus a deep, robust circadian rhythm. Is that your sleep is light, and your alertness is light instead of deep sleep and robust alertness.


Sleep is actually a ... Excuse me. Physical activity is a pretty vital component in input into getting that robust cycle. How and why? Well, there's probably multiple factors. One of them is just physical activity and energy expenditure and perhaps even daytime exposure, generation of nitric oxide. Perfusion of muscles. Also, brown fat activation. Particularly potentially one of the reasons why outdoor exercise with greater variability in environmental temperatures might be one of the reasons why exercise outdoors is healthier than exercise indoors.

We have this sleep homeostat, and there's multiple different factors that are contributing to this sleep pressure, that build up over the day, and then at night wears down, back down to baseline, hopefully if you sleep a complete amount. The reason why we don't get sleepier from the moment we wake up is because we have a circadian rhythm for alertness that is counteracting it at every step of the day. That's why circadian alignment for alertness is really important, because if your timing has shifted, the timing of your alertness rhythm might be mismatched to the generation of the sleep pressure, so you're just sleepy across the day.

If those are very tightly matched, you'll wake up, and you might have sleep inertia for an hour, meaning you're a little groggy for the first hour of the day, but it's how you feel from that point until you go to sleep again, which is really what we're looking for in terms of good quality alertness. When you have people that, for example, do a lot of travel across time zones or have social jet lag, they may become adjusted to having just lower quality mental performance day by day. Sometimes people don't actually experience notable sleepiness. They might feel a little bit sleepy, but their major cognitive impairment is altered decision making or altered risk-taking behavior or altered mood.

Those are all things that are quite sensitive, and it might look different for an individual. I worked closely with somebody in the past where if I don't get enough sleep, I feel sleepy. This person could get very little sleep, perform okay, but would make decisions that weren't aligned with this person's common behavior set, common decision set. That was very interesting to observe after I became sort of attuned to this from a scientific perspective and then observing it in the wild, if you will.


I think one manifestation of a poorly aligned circadian rhythm is nocturia, so because all of your rhythms are not operating in sync, think of a symphony playing, but they're all mistimed. It's not going to sound good. It's not going to work well. One manifestation of a misaligned circadian rhythm is the desire to wake up and urinate in the middle of the night. Now that tends to happen. There's other reasons for that as well. It's normal to wake up 15 to 20 times per night. As you age, you remember more of those awakenings that you do when you're younger. When we're young, every time you turn over, that's a microarousal. That counts, but the likelihood that you're going to remember those arousals and have greater what's called wake time after sleep onset, so once you are awoken, you stay up longer.

There could be some hormonal issues. There's also some behavioral issues. Habits are more than just putting on your shoes and going for a run. A habit is looking at pass behaviors repeated multiple times over different days, and your body creating efficiencies of those patterns. It could be patterns of thought. It can be new patterns of physiology. If you wake up and you urinate at 4 a.m., if you do that for four days in a row, it might not be hormonal that's driving it. It might just be behavioral, and your body is now prepared to do that activity at that time of day because you've done it several days in a row before that.

I've been very optimistic about quantified self really since its inception, and there are clear misunderstandings of its utility. The first level of utility is wearing these devices, getting information on yourself, and then setting goals. The goal setting part by itself is valuable. I want to be in bed at this time. You have some indication of trying to then create reliability and low variability in the time that you go to bed. We know that that's a factor in both health and mental performance. Now you have this device and through the process and the, hopefully, the user experience of setting one of these quantified self devices up, it's now helping you form that goal, and it's then reminding you in the moment, in certain moments, that yes, you said you wanted to be in bed in an hour, and we're sending you a notification to do that.


It's helping to modify your behavior. The next generation, as the signal quality becomes more robust, so multiple different signals triangulating to then give a sort of higher quality indication of what's happening physiologically, that's then going to lead to better prediction of saying okay, here are the things that you do during the day that actually influence the quality of your sleep at night, and then here are things you can do to actually improve the quality of your sleep. I think what we will see eventually is when these services can run statistics on months of data on you and we avoid the peril of last night I ate peanut butter at 8:00, and I slept really well, and I'm going to eat peanut butter every single day, and you basically have false positives, right?

Right now, in a time where we're having more false positives and false negatives in terms of the signals and what they mean, over time, as the quality of the signal improves, and we have more time to run statics on you, the device can say, "We've been monitoring your activity for a while, these things matter, and they can help you attend and focus on things that actually help you get good sleep, aside from just your behaviors. That's pretty cool too, and that's I think we're going to see more of that. Again, we live in a mismatched world, right? Our world and all those forces and pressures that we have, cause us to live in a way that's not natural, and to the degree that technology can help us live more naturally, I'm all for it.

We know that not all devices are created equal. What I like so much about the Oura ring is that detecting certain signals from the finger seems to have advantages over detecting the same signals at other parts of the body like the wrist. For example, with the aura ring will sample 250 times a second on the arterial side of the finger. It's sampling things like pulse wave. It's sampling temperature. It's sampling movement through actimetry. All of those things then will better predict what stage of sleep that you're actually in. I gave a talk at the University of Washington earlier this year, and in that talk, I discussed how devices like this can actually help us understand what natural sleep looks like.


Polysomnography is the gold standard. It's 27 leads on your body, so you have multiple wires coming out of your head, on your face. There's even one called the pez, which puts a wire down your throat to measure breathing rate. How anybody can sleep with a sleep study is sort of baffling to me. What a sleep study does is it's good at detecting signals that are important for the prediction or diagnosis of a certain condition. Movement, breathing rate, obstruction, oxygen saturation, and of course electroencephalography or brain wave detection. But it's the Heisenberg principle, right? The more closely you try to study something, actually the harder it is to then of course detect it. The observer affects the actual thing that's trying to be measured.

The more frictionless this is, the better ... I think that the potential for the aura ring to actually tell us what natural sleep looks like it better than PSG for sure because people can wear these, forget about them, and it then over periods of months to quarter to even years it can say this is what your sleep actually looks like. We know that we want to have high homology or overlap with what PSG tells us in a very controlled environment, and once that reaches a certain degree of ability, then we're going to have a lot more people wearing these devices in ecologically relevant settings, and we're going to learn more about sleep than we ever have.

This has huge potential to help us as a population, as humanity understand what natural sleep looks like in different scenarios, what natural sleep is, and then we can use that information to counteract the personal information that you're getting and then all of it can then hopefully help an individual have better health across their lifespan.

Yeah, so the things that matter for sleep are timing, intensity, and duration, and what does that mean? The time where your sleep occurs, the intensity of that sleep, meaning the stages that you get into, the depth of those stages, how those can catenate to one another, sleep continuity. All of those do matter, and some of them are directly controllable, so you can go to bed at the same time and you can plan to have enough time in sleep. We just addressed two of those. We addressed one, which is the timing of your sleep, right? If that's consistent, that's good. We can also then plan to have what I call complete sleep, which means that you're waking up naturally and not by an alarm, so you're not going to get eight hours of sleep if you're in bed for six hours. We know that.


I'm not using eight hours and six hours as necessarily bad and always good, but those are kind of common ways to discuss sleep time. You can look then at things ... and then the other things that matter too is smart light rhythms, day, evening, and night. You want to get adequate amount of daylight exposure, so at least a half an hour outdoors has sort of a Pareto principle about 80% of the benefit of that anchoring your circadian rhythm happens in about 30 minutes outside.

You want to modify your light environment in the evening so that the tone and intensity of light is changing, so the intensity of light is diminishing. The tone is becoming more like fire. Think about what a natural exposure is, being outside exposed to the ... What are the colors of fire? They're orange; they're amber, right? Then at night, you want to keep your room relatively dark. Our eyelids are translucent. Light can go through our eyelids and affect our circadian rhythms, so if kids want a nightlight, keep it extraordinarily low intensity and also amber toned. If a nursing mother wants to feed their child, that same light is going to be really important just so that they can see.

Minimal light necessary to be able to see. All that's really good. Now these devices really depend on the ecosystem that they're connected to. It's the ecosystem then that gives ... If you just wear this and it's collecting all this data on the sleep and you're not getting feedback, it does nothing for you. Oftentimes, that serves as a control in clinical trials that are looking at these devices and their impact on some parameter like increase in steps or improvement in sleep quality. You have to be able to get that feedback. You have to set your goals, then perhaps modify them. I thought I needed six and a half hours in bed, but I tried experimenting with longer time, and I noticed that if I slept longer, I felt better.

Having that in a form of experimentation I think is good . it can lead us down some rabbit holes. It can lead us astray, but ultimately, it's engagement. You're engaging with your own ... with aspects of health that matter, and so a big part of what I do with HumanOS and it's based off of this behavior model that I created, it's looking at why should you do something, how do you do it, are you doing it, and is it working? Once you've learned the value of something and you've developed some skills around that understanding or that activity, how do you stay engaged where three or four years later you're still doing the things that you believe and understand to be valuable?


Now we know life gets in the way. We've got family pressures. We've got job pressures. Things like this can just help you to stay engaged with a lifestyle pattern that you believe is healthy with better fidelity. We know that. We know that work by Albert Bandura showed he'd the fourth most most cited psychologist of the 20th century. That the more that we ... People's ability to achieve an outcome is proportional to their ability to define a specific goal and get specific feedback about how they're doing. You have that idea of what gets measured gets managed is true. It's true. Now we've got to be selective because we can measure things that don't matter, so we don't want to just measure everything.

We also can't measure everything that does matter, right? If you keep that sort of balance in mind, I like to keep it simple. While the sophistication of these devices is increasing, and I'm excited about what could happen with them, a lot of the value is simply wearing, engaging, and helping it change you, your behaviors, versus thinking it's going to do things for you. In the future, the ability for these devices to do that will improve. I'm not waiting for that now because the majority of the benefit is just helping me align with stuff that I know to be good for me.


interview with dan pardi...interview with dan pardi i'm dan pardi. i do sleep research, and i...

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