Ideas - Could resetting the body's clock help cure jet lag?

Episode Date: April 29, 2024

Canadian PhD graduate Kritika Vashishtha invented a new colour of light and combined it with artificial intelligence to fool the body into shifting time zones faster — creating a possible cure for jet lag. She tells IDEAS how this method could also help astronauts on Mars. *This episode is part of our series Ideas from the Trenches, which showcases fascinating new work by Canadian PhD students.

Hey there, I'm Kathleen Goltar and I have a confession to make. I am a true crime fanatic. I devour books and films and most of all true crime podcasts. But sometimes I just want to know more. I want to go deeper. And that's where my podcast Crime Story comes in. Every week I go behind the scenes with the creators of the best in true crime. I chat with the host of Scamanda, Teacher's Pet, Bone Valley, the list goes on. For the insider scoop, find Crime Story in your podcast app. This is a CBC Podcast. Hello everyone, this is John. Hey John and Tom. Hi, Pauline. From CBC Radio.

Welcome to Ideas. I'm Nala Ayed. We're all putting these things on our feet? Yes. Why are they blue? We don't look at the colour as long as it keeps all the dirt from progressing inside the cabin. Ideas producers Tom Howell and Pauline Holdsworth entering a repurposed airplane hangar at Downsview Airport in Toronto. There's this beautiful kind of sky blue floor, really tall ceilings, fans going everywhere.

Yeah, like as it used to be a hangar, it does get really hot and cold. So, but yeah, other than that, it's just different projects that are going on here. I can see an airplane seat that's just sitting out on its own. By the way, that project used to be mine with that black tower. It was a small project

where I actually tested different lights to see how they can inactivate coronavirus. actually tested different lights to see how they can inactivate coronavirus. Kritika Vashisht just completed her PhD in aerospace engineering. She spent the past three years in the laboratory at Advancing Engineering Research and Innovation in Aerospace, where she was pursuing a cure for something almost all air travelers have experienced, jet lag. Kritika is fascinated by light. In fact, light is the deeper focus of her research.

It's a fundamental framework that I've created, and it could be used in medical fields. You can create personalized light systems or light schedule to treat circadian rhythm disruption. Most adults in industrialized societies are chronically sleep-deprived. Now we know that there are multiple clocks in the body, and some of them might respond to other types of cues. Light penetrates everywhere. What's the darkest part of my body? Maybe that's another episode.

Yeah, maybe your bone marrow. I'm not sure. On today's episode, resetting the body's clocks. It's part of our series, Ideas from the Trenches, where we feature the outstanding work of Canadian PhD students and meet the scholars who inspire them. And welcome on board. Okay. So you can listen to this laboratory. Yeah, but I'm just going to open and turn on the standard lights that are there in an aircraft cabin.

Kritika Vashish brings us inside what used to be a large passenger airplane. Yeah, it's actually a real aircraft. Yeah. I mean, you wouldn't fly it now. Yeah, so we don't really have the cockpit, so it's just the cabin part that we have. It smells like an airplane. Noticeable lack of wings. There's a few reasons I wouldn't fly in this. Yeah, so this is the corner that we have set up for the light simulation.

I just got terrified. Her name is Barbara. Barbara is a mannequin placed at a window seat a few rows down from where we're standing and we actually use her to mimic as if a human is sitting there and at where you would measure certain illuminance at your eye level so very realistic especially her glasses and the buttons on her shirt oh yeah actually it's one of my colleague's top that she's wearing. And she's got a window seat? Yes.

And where would you sit if you were... Oh, I sit there to control all the lights. Kritika needs to control what type of light is striking Barbara's plastic eyeballs, and how much light is striking them, and when. This gets to the crux of her PhD thesis and its ambitious goal, using light to cure conditions like jet lag. I have basically developed an optimized light exposure schedule, which I'm going to show you the demonstration.

So what it does is that if you, let's say, have a have a 10 hour long flight so rather than just constantly having your lights on it would be optimized in a way that it's either on off or high intensity low intensity in that way you're going to have a schedule for 10 hours so that when you land in your destination time zone your circadian rhythm is little shifted towards your desired circadian rhythm. If you're flying from LA to London, you're going to have, like, depending on when you fly, you will have a jet lag of eight hours. So what that means is that your internal body clock cannot really shift with the speed we are flying. So our body clocks remain still in the local time zone whereas we are physically in our destination time zone so we're going to talk a little bit later about you know what jet lag is

and why we experience it but i'm just curious why light what got you really interested in light okay so uh that's a good question because uh a circadian rhythm it has like uh like many zeitgebers which means many stimulus you gotta say that again it's uh called zeitgebers, which means many stimulus. You got to say that again. It's called zeitgebers, which is a German word for stimulus, like external clue. Light is considered one of the strongest synchronizers, like a strongest stimulus for our circadian rhythm. So as other things like your meal timing. If you eat your meal, let's say at 5 p.pm, which is a little off time to have your lunch.

So it would have a different effect on your circadian rhythm. So same way the meal timing and your exercise timing and the light, they all act as a stimulus. We basically focus more on the light because the existing literature in the medical field supports that the light does act as a stronger synchronizer and it's also non-invasive. So you don't really have to push anyone to either do something or to eat something. It's just that they're sitting there and you're just changing the light pattern. So that was a big reason to choose light. The other reason for using light as a cure for jet lag involves your pineal gland. The pineal gland is working right now approximately in the very middle of your head.

Among its jobs is to convert the brain chemical serotonin into another brain chemical called melatonin. And for some reason, this gland reacts to what your eyes are experiencing. It seems to enjoy being in the dark because when your eyes see light, this pineal gland responds by getting depressed and it doesn't work nearly as hard and its melatonin production goes way down. Kritika's research involves examining how best to make use of this relationship. So what happens is when you suppress your melatonin, it makes you more alert because melatonin is known as a sleep hormone, right? It creates the sensation when you have high melatonin, it makes you less alert, more towards subjective sleepiness. So say Tom and I are here as participants, when we walk in, you know, what would our typical experience be in this lab? Okay, so there are a

few criterias that you have to fulfill, like you should have a regular sleep-wake cycle, you shouldn't have traveled internationally in past one month you should not be working as a shift worker and also no eye disorder kind of thing no alcohol consumption you know there are certain criteria and when you fulfill that you kind of sign consent form and then you come inside the cabin i'm gonna again go through all the consent requirements and so there's this 15 minutes period where where it's really low light intensity so that you get accustomed to this setting and then slowly we increase the light intensity and you have to sit here for four hours uh we usually recommend participants not to use the washroom but if they had to we kind of give them blue light block sunglasses they have to go in the dark you're saying no they have to just wear them which blocks the blue light and they're not allowed to

eat anything they're not allowed to have coffee or any caffeinated drink. This is fun. And so do people meditate? Do they talk? No, actually they're not allowed to close their eyes because you are having the light exposure, right? Yeah, they're allowed to talk. They can talk. Can we make Pauline do this? Can you shine lights at Pauline right now?

I can. Okay, let's do it. Let's make you go through this. Okay, so Pauline's going to take a seat next to Barbara, I guess? Is it okay for me to sit right next to Barbara? Yeah, you can. You can sit anywhere. Okay. Okay.

While I settle in next to Barbara, Kritika sits two rows ahead of me at a computer. Okay, so I'm going to have the, like a constant light exposure. The computer controls a strip of LEDs running along the side of the cabin just above Pauline's head. You'll see because when participants come here, they are usually having a constant light exposure. They don't really see this variation. exposure, they don't really see this variation. The brightest light on me right now is actually the sun, streaming through the window beside Barbara. Do you want to see the window first?

I think so. Tell us what you're showing us and then show it. Okay, so right now I'm just just gonna show you how the window works so you just made that window that's next to Barbara turns super what's getting close to a midnight blue yeah so it so it's going to get real dark. The transmittance level is 99%, so you can actually block 99% light. Okay. Yeah. We don't really go that dark.

The way it's controlled is that you pass the voltage through it, and it keeps getting dark, but we never actually test it with the maximum voltage, just because we don't really want to take a risk and fry it. Sunlight is very dynamic. So it's just changing every minute. Sometimes it can get cloudy. Sometimes it's super bright. And also, let's say you start flying in the afternoon.

So when you're flying, you will also have this transition where it's evening, right? Or where it's, again, morning all the time, depending on where you're flying, you will also have this transition where it's evening, right? Or where it's again morning all the time, like depending on where you're flying to. So like it's just so dynamic and you have to in real time keep measuring it and also ensure that based on that you're not abruptly changing either the transparency of the window or even the intensity of the lights to ensure that you don't really cause any kind of visual discomfort. With the sunlight under control, Kritika starts to manipulate the LEDs. Essentially, in a cabin environment,

like in an aircraft cabin environment, there are majorly only these two sources of light. Like, you still have other sources like your phone or the screen if you're watching a movie but like we are controlling only the natural sunlight that comes in and the cabin interior lights with the purpose of exposing only the optimal light that is required for your circadian shift why does barbara need to be there? Sometimes, so like for measuring the glare or when you are taking any measurement,

it is the eyes that perceive the light. So you have to measure how much light you're actually getting at your eye level. Because the light disperses, so light intensity here at this point A and point B can be different. So we use that as an average person or average human, and we just put the sensor right next to her eye. And so are the lights changing right now? No. The LED lights change color slightly,

and I'm sitting in a warmer shade than the regular cabin lights from before. So far, I'm enjoying the LED track lighting. I find this a comfortable light. Yeah, me too. I mean, when we first came on, there is that kind of feeling of being on an airplane, but this is more chill. This is more nightclub. This kind of mood lighting. This whole research, it's divided in two parts. So you do want to have the face shift, but you also want to maintain a visual comfort. I see. It's one thing to cure people of jet lag, but not if you give them some sort of seizure in the process. Yeah right so because it's a common assumption that more light you have

more phase shift you can get but if you really shine extremely high intensity light let's say 10,000 lux or more than that that is actually very uncomfortable to sit if you're sitting for a long time. That's what makes it a typical multi-objective optimization problem. That's what I'm solving. 10,000 lux, that would be more like what they would use for a seasonal affective disorder lamp, which you're only supposed to have for a set amount of time. Like in a long-haul flight for 10 hours or more than that, you can't really expose someone to that light.

Yeah. So your job in this lab is that you need to be able to control exactly how much light and what kind of light is hitting the eyeballs of a dummy or a real person but how do you know if the light that you're doing is even having any effect on their circadian rhythms okay so because melatonin which is considered the gold standard for circadian rhythm study it's not easy to measure you need a proper clinical setup because either you can measure it through your saliva sample or through plasma which is your blood and that kind of makes it difficult to do and you would require some sort of clinical assistance whereas

the mathematical models that we use their main state variable is core body temperature it's easier to kind of relate with that in reality would have pauline hooked up to various measuring things right to check her body temperature yeah so in reality she would had been using um a core body sensor from past three days from past two days now when you say a core body sensor that sounds like you have to stick something inside you yeah but uh that's actually um from a very new company. And they somehow use the heat flux to actually estimate what your core body temperature is. But you're right. Core body temperature means your temperature of your organs. So you either have to, like the conventional way is either a rectal thermometer.

Pauline, you agreed to take part in this. Or like a pill. You eat that. When do they get told there's a rectal thermometer involved i don't use that oh sorry i understand you have the clever the new one so you have to just stick it on your skin well that's good news for you excellent news My name's Bruce Malek. I'm an industrial designer at Bombardier Aerospace. A lot's been done in developing a whole bunch of new wavelengths of light,

and that's driven all these beautiful lights, LED lights that you have today. Bruce Malek designs airplane interiors. He also loves playing tricks on us with lights. To make the plane feel taller, we slowly adjust the intensity on the headliner, which is the ceiling of the aircraft. We bring that up a bit brighter. And it's in nuances. It's visually, you can't really see it, but you can feel it. And the sidewalls, the side of the cabin, we'll dim those a little bit.

cabin, we'll dim those a little bit also so that you don't really see it. But when you come in, you feel that it's a much taller environment than it actually is. And then when they go to sit down, you do a transition from height to width by playing now with the intensity of the width of the aircraft on the sidewalls and lowering the headliner and that will actually make the cabin feel wider. So it's all these nuances but if you do flip a switch then everyone's going to notice.

Then everybody's going to notice and it doesn't work. Can you do anything to make it seem like I've got more leg room than I have? We also put lights around the footwell so around where your feet are. So that makes you feel that there's more room for your feet. That's a nice little play on making you feel like you got this big opening underneath your feet to stretch out your legs, but it hasn't changed. It's just more light. The illusion works until you kick the person in front of you, I guess.

Bruce Malek's job makes him extremely interested in what light can do to shift our circadian rhythms during a flight. The wavelength of color acts on the receptors in the back of your eyes, basically. I'm making this really basic. Please. Acts on the receptors in the back of your eyes, which control through the sciatic nerve to the back of your brain,

which controls your production of melatonins. And your melatonin is what makes you awake and what makes you fall asleep. And if we can control those, we can wake you up early or we can help you fall asleep. The work that Kyrgyzika has been doing is playing with those and looking how we can use those color waves to offset your body clock, your circadian rhythm.

When you fly from Canada to Europe, you get a jet lag. So that jet lag is five hours. But Kiritika was able to prove on a four-hour jet lag, she can modify your circadian rhythm by two hours. Your body's adjusted to the light at the destination by two hours. That was the beauty of Kritika's research. She proved that this system works, and she proved that with these formulas that she came up with we can measure it and adjust it for every type of person Ladies and gentlemen

now that we're safely in the air and we're on our way to Port Elizabeth it gives me great pleasure to once again welcome you on board if there is anything that we can do to be of assistance to you please don't hesitate to ask A big problem with shifting our circadian rhythms is that our body's internal clock is conservative. It doesn't like changing its ways immediately. Its nature is to slowly alter its habits.

If you don't have the patience for that, and you want it to change more quickly and easily, to get over jet lag, for example, you might need to trick it. Hi, I'm Jamie Zeitzer. I'm a professor at Stanford University. Rumor has it that you've cured jet lag. How close to the truth is that? We're getting there. We're getting pretty close. We can cure short jet lag. How close to the truth is that? We're getting there. We're getting pretty close. We can cure short jet lag.

How about that? We can cure jet lag of, say, three to four hours. We're still working on the eight to nine hour one. Jamie Zaitzer's research has led to a consumer product called the Lumos Smart Sleep Mask. You strap it over your head like a regular sleep mask, and it flashes lights through your eyelids while you sleep. It came as a bit of a surprise to Jamie when this worked. We're not sure why.

I mean, flashes are not something that the circadian system evolved to respond to. But the cells that respond to light are kind of unusual in that they have very long off times. And what I mean by that is that when you expose one of these cells in the retina to light, these are the cells that are going to kind of respond to light and transmit the light information from the eye to the brain. When you expose one of these cells to light, they don't turn off. So you turn the light on, then you turn the light off, and these cells continue to fire.

And that's kind of weird. I mean, so if these were used for normal vision, it would be like you turn the lights on, then turn the lights off, but you kind of still think you're seeing light, but you're not actually seeing light. And that's kind of what these cells are doing and enables these cells in the eye to basically integrate light over time. So you're getting a lot of light over time, and it's kind of getting a gestalt of how much light you're getting. So that's how the basic system is working. And when you're using these flashes, basically what you're doing is you're

optimizing the response. So you're giving this flash of light, and then in between the flash of light, and these are not rapid flashes, this is not a strobe light. These light flashes, usually depending on the exact protocol, or anywhere between once every 10 seconds and once every 30 seconds. Between these flashes, this darkness between the flashes, the various cells in the eye, specifically the cones in the eye, they are basically readapting to the darkness. So they're resensitizing. Think of like when you're in a movie theater and it's all dark, and then you go outside and how bright it seems when you first go outside. And that's the sensitization process. If you're giving normal, long duration, normal light exposure, the cells kind of inure themselves to the light

relatively rapidly and you're getting most of the response in just the first few minutes of light exposure. And so by giving these flashes of light, we are basically able to fool the system into thinking it's a much, much bigger stimulus than it actually is. And this is happening while people are asleep. Doesn't it wake people up? No. So we've done this when people are awake and asleep. And if you're awake, it's annoying. Not something I would suggest sitting in front of. I've done this for many hours and it's not the most pleasant experience when you are awake getting these camera flashes in your eye. But when you're asleep, it doesn't. We've tested this in lots of people. We can't find any substantive changes to sleep and it doesn't seem to wake people up. So when you're giving these light flashes, light can pass through your eyelids. About 90% of light

is cut out. So only about 10% goes through the eyelids. Mainly red light and to a lesser extent green and blue light go through the eyelids and can activate these cells in the eye. That information then goes into the brain and goes into various parts of the brain. And kind of the parts of the brain that are responsible for responding to external stimuli, for the most part, they don't wake people up. Now, will it wake anybody up? Absolutely. There are people who are definitely sensitive to light exposure. There are people who are more sensitive to sound and they will be woken up. Now, you have a lot of people who, when the sun comes up in the morning, a little stray

beam of light comes into the room and they wake up immediately. So some people are very sensitive to light and they're probably not participating in the kinds of studies or using this kind of mask. But I would say probably about 95% of people, they don't tell us anything. And when they're in laboratory, we don't see any evidence of them waking up to the light. I mean, how did you get into this? Because it doesn't seem, well, whatever. What do I know? I don't know what seems obvious and what doesn't, but how did this start? You're absolutely correct. This was basically a conversation between a colleague of mine, Craig Heller, and I.

I had just gotten to Stanford as a postdoctoral fellow, and Craig has been in the field for a long time, and he had done this study, and I've asked him this question, and I still haven't gotten an adequate response as to why he did this, but he did it in mice. Did this? What do you mean, did this? Did this study with flashes, you know, gave flashes to mice. And I said, well, why'd you do it? And he's like, I don't know. We had the mice, and our original experiment didn't work, so, you know, whatever.

We had the mice. That's great. it worked, so, you know, whatever. We had the mice. That's great. You know, I'm sure there was some interesting beverages associated with the design of the study originally. Jamie Zeitzer of Stanford University. His research into flashing lights through your eyelids gave rise to the Lumos Smart Sleep Mask.

On Ideas, you're listening to Resetting the Body's Clocks. This episode is part of our ongoing series, Ideas from the Trenches, where we showcase fascinating research by Canadian PhD students. You can find Ideas wherever you get your podcasts, and on CBC Radio 1 in Canada, across North America on Sirius XM and US Public Radio, U.S. Public Radio, and in Australia on ABC Radio National and around the world at cbc.ca slash ideas. I'm Nala Ayyad. Hey there, I'm Kathleen Goldtar, and I have a confession to make. I am a true crime fanatic. I devour books and films and, most of all, true crime podcasts. But sometimes, I just want to know more. I want to go deeper. And that's where my podcast, Crime Story, comes in. Every week, I go behind the scenes with the creators of the best in true crime.

I chat with the host of Scamanda, Teacher's Pet, Bone Valley. The list goes on. For the insider scoop, find Crime Story in your podcast app. Jet lag is a tiresome side effect of long airplane trips. It normally takes us a while to get over it. It can feel rough even when the switch is just between regular and daylight savings time. So it's no wonder that leaping four, five, ten time zones in one day really throws us off. Kritika Vashish took on the job of finding help for long-distance flyers. It was the focus of her PhD in aerospace engineering at Toronto Metropolitan University.

Kritika now rejoins Ideas producers Pauline Holdsworth and Tom Howell. Hi. Kritika's been listening to everything we've heard so far, and since we've recorded that scene in the airplane lab, I understand you've completed your PhD, right? Yes. I'm currently at Harvard doing my postdoc. Congratulations. Thank you so much. How did your defense go? Did they ask you more sophisticated questions than we ask you? It went well, but I think like as any defense is,

it was hard. It was a lot of questions. I passed it, so I would say it went well. And Bruce Mallett gave us an idea of the results of your research, but can you remind us exactly what you succeeded in proving? So we were able to see that the efficacy of our light and there was a shift of two hours, approximately two hours. Obviously, if you're flying for 10 hours, you're probably going to have a jet lag of eight to nine hours, but you are still able to kind of reduce that. Whereas before it was like nothing. So yeah, I feel like that's a good step towards it. And the second part of my research as the title was personalized model. So we also wanted to take into account age and gender or the chronotype and like further optimize the light model.

So, yeah, that was the second part. So here's a frightening question. Jamie Zeitzer told us that they're getting closer to curing jet lag with this sleep mask that flashes through your eyeballs. Very different approach. Are you worried he's going to cure jet lag in a different way and then we're not going to need your research at all? I mean, it's very fascinating. I didn't actually know about that research before I heard this, but no, not really. I think in general, I feel in science, it's all about learning.

And if we could do that with the sleep mask, it's great. You know, at the end, the whole point is to solve the problem of jet lag. Is there any chance, because as I understand that you use that mask when you're asleep and your eyes are closed and in your research, we're talking about time you're sitting on the flight and your eyes are open, right? In your study, you have to keep your eyes open. Is there any chance that we could add like his two hours and your two hours and get people to shift four hours? Or is that too simple? I actually don't know.

But maybe, you know, different systems and different models could be integrated to see how that would impact. But best to my knowledge, I think there is also your bodily restrictions that you can't really shift. I think, hormonally speaking and internally, you can't really, you know, just shift in a day. 10 hours of jet lag, you can't just shift in a day. But if in future we are able to, then that would be great. So you were telling us about the second strand of your PhD research around personalizing. Why does your light schedule need to be personalized? Why isn't it the same schedule of lights for everyone on the same flight?

Okay, so that part of my work actually gets inspired or comes from Dr. Jean Duffy's work. She has been recently appointed as a professor at Harvard Medicine School. One of her work was where she was saying age-related differences in your circadian rhythm, like when you're exposed to light. And also, it's not just the age. There are other factors as well, like your gender could also play a role, like males could be more sensitive or less sensitive compared to females, to a specific light exposure or your chronotype, which is essentially your sleeping pattern if you're a morning person

or an evening person. Dr. Jean, she has done some amazing work in kind of figuring out the inter-individual differences in your circadian rhythm, and that kind of also played a strong background for creating this personalized model. And you're at Harvard now. Are you seeing her in the hallways? Yeah. Like, luckily, we are in the same team. So, yeah, that's like a dream come true that people who I really looked up to, I'm actually able to work in their team and with them. That's so exciting.

I'm Jean Duffy. I'm a professor of medicine at Harvard Medical School and a clinical researcher at Brigham and Women's Hospital in Boston, Massachusetts. Just to get us started, can you describe the lab that you work in? Describe it in what way? Physically. Physically, as well as the kind of work that you do there. Okay. We have five separate study rooms. They're designed for doing sleep and circadian rhythm studies in a special way,

They're designed for doing sleep and circadian rhythm studies in a special way. So they have special soundproofing so that noises from the outside don't wake participants when they're sleeping. They have very precise lighting control so they don't have windows so that the light isn't coming in at different levels at different times of day. And they have ceilings that are completely covered with lamps that we can control how much light those lamps output, anywhere from very dim levels of light up to very bright light, much brighter than normal indoor light. Each participant is studied separately in one of these study rooms. And their studies last anywhere from just overnight to the longest studies that we've done have been up to three months where their participant comes into the room and just doesn't leave for the three months until their study's over. How much would you have to pay someone to put themselves through that?

Well, so some of the very long studies, the participants get many thousands of dollars for taking part in them. Obviously, they do it for the compensation, but they tend to also do it because they're either interested in science, interested in sleep and, you know, their biological clock, or yeah, just want to, you know, take part in something interesting. One thing that we've been trying to understand is why we have a circadian rhythm in the first place. Is there some kind of evolutionary advantage or other advantage that it gives us? So yeah, it's thought that there's an evolutionary advantage to having these clocks because really they're found at all levels of organization from some single-celled organisms to insects, plants,

mammals, and so forth. And if you think about it, all life forms evolved on this really strongly periodic planet that we live on where there's, and then there's darkness. And along with the light, there's changes in humidity and temperature. If you have an ability to know when the light is coming, if you're in the dark, and you know when the light's about to come, and you can be prepared for that, you're likely going to have a better chance of finding food or finding a mate or whatever, all those things that contribute to your survival. Those are obviously theories, but there is some evidence from studies that can be carried out in organisms with short lives,

where you take the organism and put it in an environment that doesn't have a near 24-hour cycle. And then you can see that they don't survive as long, they don't do as well, those sorts of things. And then the reverse types of experiments have been done where you can either find mutant organisms that have, instead of a 24-hour clock, their clock is either shorter or longer. clock, their clock is either shorter or longer. They survive better in an environment with the cycle length close to their internal clock length and worse on a 24-hour environmental cycle. The circadian rhythm gets its name from the fact that it takes about a day for your body to cycle through various biological processes and begin them all over again. Circa means thereabouts, and DA means day, so circa DN means literally about a day. Weirdly, almost no one's body clock is on a precise 24-hour cycle. For the vast majority of us, it's already slightly off. That's the very interesting thing. Every species has a range that's near 24

hours, but not exactly 24 hours. The studies that have been done so far in humans, the range seems to be somewhere between about 23 and a half to maybe up to close to 25. So each individual person has a slightly different period. And on average, sighted humans have a period of about 24 hours and 10 minutes. Do we know any personality traits that go along with having a longer clock? Not necessarily personality traits, but predisposition to certain kinds of sleep disorders and sleep problems. And so if you think about it, we have these clocks that aren't exactly 24 hours. But if we're trying to live in a 24-hour world, then our clock has to be reset a little bit each day for us to stay in sync with the external light dark cycle day you know day night cycle and so the longer your internal clock is away from 24.0 the harder it is or the you know the bigger

resetting you have to do every day to stay in sync and the more likely it is that you can kind of get out of sync. One of Jean's big areas of research is trying to help people who do shift work on a constantly changing schedule. People who work the night shift, you know, they're trying to stay awake all night and be at work when their physiology is promoting sleep. And then they go home in the morning, they're exhausted from having tried to, you know, stay awake all night and they go to sleep because they're really exhausted, but they typically can't stay asleep for more than four or five hours because their biological clock thinks it's the daytime and wants them, you know, wants them to be awake. And so on average shift workers are getting one or two hours less sleep than even the normal sleep deprived people are because

they're kind of fighting against these cycles of sleep promotion and weight promotion that are coming from their biological clock. We know that there are changes in metabolism that can happen fairly quickly within a week of just not getting enough sleep night after night. There are also changes to the immune system that make us more vulnerable to things like viruses or make us take longer to develop antibodies to a vaccine. And there are some also changes in our cardiovascular system in like blood pressure and heart rate and things like that. Many other factors can affect a person's circadian rhythm beyond the hours they work. Different people are on different schedules.

We even experience slightly different lengths of day according to our body's needs. And we see this in a lot of blind individuals. Many blind people who don't have any light perception drift slowly in and out of sync with the 24-hour day. And so they'll go through cycles where they're in sync and so they can sleep well at night, stay awake during the day, but then they start to drift out of sync. They're very sleepy during the day, may have to take naps in order to cope, and then they have a lot of trouble sleeping at night. And then they'll gradually cycle back around to being in sync again

as their clock kind of drifts in and out of sync with the 24-hour day. And to make matters even more complex, in addition to the variation between different people's internal clocks, there's more than one clock to worry about, even inside one human body. Every single cell in your body is actually running a small molecular oscillator that keeps 24-hour time. that keeps 24-hour time. My name is Rosemary Brown. I'm an associate professor at Northwestern University where my lab works on computational methods for analyzing high-dimensional data, including data that you might get from wearable devices or biomarkers in the blood. Rosemary Brown's team has developed a blood test that essentially helps tell what time it is inside somebody's body.

Blood cells themselves are running this little molecular clock. And so what we're able to do is measure the levels of genes that are expressed in the blood. Those genes change their levels periodically over the course of the day. And so by measuring their levels, we can then infer physiological time on an individual basis. Okay. And is it actually expressed as a clock time or what's the reading? Yeah. So it's expressed as a clock time. That clock time that the machine learning model outputs can then be compared to the clock on the wall or the clock time that you were at some point previously, right? in order to assess

how well aligned you are with your current environment and how that might change if you're treating a circadian disruption. One of the things that we're interested in now is can we get read outs of these different clocks and then start to ask, do we find evidence of good internal synchrony in an individual or desynchrony in an individual? One of the things that we know from epidemiological studies and clinical studies and people's experiences is that as we age, circadian rhythms tend to become a little bit more damped and a little bit disrupted. People start to experience more sleep disruption as they get older. And so one of the questions we have now is, does that arise from an internal desynchrony within an individual? Ongoing research in our lab and

others are starting to probe how well synchronized are the various tissues in an organism and how does that change with age? The fact that we have so many internal biological clocks, each of them affected by different stimuli, also has important implications for treating jet lag. When people have modeled jet lag in the past, they've thought about the central clock in the brain, the input to which is the light that you see, right? So that's how that circadian rhythm in the brain is reset. Now we know that there are multiple clocks in the body, and some of them might respond to other types of cues. So it's thought that the clocks in your gut might be responsive to when you eat. Mouse studies have shown that clocks in muscle tissue are responsive to exercise.

And so now we can start to think about how all of these different cues could be brought together in order to help somebody recover from chat lag. Last year, we published a mathematical model that described two populations of clocks. These were meant to model the clocks in your brain and the clocks in your gut. And in this model, we had two different inputs, the light input and the meal input, which we could vary mathematically differently. And we could ask, well, what does this model tell us about the speed of jet lag recovery depending on different meal schedules. What the model showed was that if you start eating on the schedule of your new time zone, as soon as you arrive in that new time zone, and really emphasize having a good hearty breakfast in the

new time zone, we believe that you should recover from jet lag faster than you would if you were eating just when you felt hungry or eating on the new time zone, but not really having a hearty breakfast, sort of spreading it out during the day. What hearty breakfast did you give your hearty breakfast? Great minds think alike. That is a great question. So this is something, unfortunately, that is a limitation of our mathematical model. It will not tell you actually what caloric intake a hearty breakfast should be. So that's something that has yet to be determined. But what we were able to do was we were able to mathematically skew the size of the input. So when that input of a meal in the morning was large relative to the ones later in the day, it showed faster recovery from jet lag. A lot of your work is really trying to understand these kind of interconnections. And I wonder what looking at circadian rhythm in particular has revealed or kind of clarified for you about the nature of this sort of complex interplay that's always going on in our bodies?

You know, I find this fascinating because one of the things I'm really interested in is how, just in general, how living systems self-organize, right? We start out from a single cell. We become this incredibly complicated multicellular organism where everything needs to be orchestrated in harmony in order to maintain a healthy immune system, a healthy cardiovascular system. And one of the ways that a multicellular organism can coordinate processes is through every cell having a timekeeping mechanism, right? I like to give the example of, you know, if you and I agree that we are going to meet for drinks after work at five o'clock, we don't need

to be in contact throughout the day saying, is it time? Is it time? Is it time? It's enough for each of us to just have a clock and show up at the same place at five, right? And so this is one mechanism, I believe, by which a multicellular organism can keep processes orchestrated without having to expend energy for everything communicating to each other. And I think we're just starting to scratch the surface scientifically about the role in which those biological timekeeping mechanisms have in orchestrating processes. I think it's an exciting time to be in this field. Have you got a sense at the moment of how possible it will be to sort of set a human clock? Like, I want to be this time, and just like on the cooker or whatever, you get to just set it. Is that something that will always be impossible,

or do you think that's something that's sort of within the range of where this mind will lead? You know, that's a really great question. And I'm actually not sure what the answer to that question is. I think that, you know, in some sense, it's important for these systems to be a little bit robust

so that, for example, on a dark day, you don't find your circadian rhythm suddenly being reset or you experience an eclipse, right? And suddenly there's a reset to your circadian rhythm. So there needs to be a little bit of resilience and robustness. And that might make it hard to come up with a mechanism that would instantaneously change the clock. But then again, we don't fully understand all of the molecular underpinnings of this. So it's possible that there would be an avenue to do so that we just haven't yet discovered. Another avenue where there are still a lot of discoveries up ahead is space. Jean Duffy had something to say about that.

The group that I work in at Brigham and Women's Hospital did a lot of research for NASA and for the National Space Biomedical Research Institute back in the 90s when the U.S. space program was planning to go to Mars. Backshell set. Current velocity is 83 meters per second at about 2.6 kilometers from the surface of Mars. We have confirmation that the backshell has separated. Originally, they were going to get there by 2014, but that didn't happen.

And there are all kinds of challenges, because first of all, the day length on Mars isn't the same as the day length on Earth. They have a 24.6-hour day. Let's say you sent people to Mars and they were going to stay there for a while. If they tended to have a shorter cycle length of their clock, they would have a hard time adjusting every day. It would kind of be like being

a blind person. Individuals with a longer cycle length would adapt better to a Mars day length. And we actually did some simulated studies in our lab where we had people living on Mars days versus Earth days and trying to see how their internal systems would adapt to those. The other thing is just in terms of circling the Earth, so being in space but in orbit around the Earth, astronauts are exposed to a 90-minute light-dark cycle when they're in orbit. And that, of course, is very disruptive to their circadian clocks. So again, the NASA Space Program has done a lot of studies to try to understand how to help astronauts adapt to that. Kritika Vazist, you are, I believe, sitting in our Toronto studio and have been listening to all of this. Is that correct?

Yes. Hello. Hello. Are you going to take your research into space? Yes. I'm really interested from a long time how combining AI with the existing knowledge that we have about meal timing or the light exposure timing and how we can just, you know, create a model and help astronauts adjust to their circadian rhythm better when they're on Mars. What are the aspects of space travel that most interest you in terms of this kind of scientific research? Oh, like in childhood, I always wanted

to be an astronaut. I did my PhD in aerospace, so I still have that interest to do something for space. Now I'm more interested in doing circadian rhythm research, so I really want to create an AI-based model to help adjust circadian rhythm better in outer space. So maybe the astronaut would talk to the AI and say how this light schedule is working for him or her and then the AI would improve it on the go, that kind of thing? a sleep log and you can through that sleep log kind of try to interpolate how much you predicted they will have jet lag and how much actually it was and then feed that as a feedback in your AI model and improve it for that particular passenger when they're flying again. It's more like learning with every trip. Speaking of biomarkers, we heard Rosemary Brown talking about the work that her team is doing to look at biomarkers in the blood

to get a readout. What aspects of the sleep science that we heard from Rosemary and Jean are the most important for you? I think if we could, because right now, as she mentioned, when you have to kind of create a baseline for the circadian rhythm, you have to have minimum of five to six points. That being said, you need to have minimum five blood samples taken or five saliva samples taken to actually create that curve and see what their natural cycle is like. If we could have a way that you just prick someone once and you can just predict their whole cycle, that would be fascinating. It would really be a great advancement in creating personalized model because you just need one point to predict how i think rosemary told us her team now has it down to two blood draws which i

think is a a big improvement in terms of the kind of data that you need yeah yeah i'll definitely look into her work it was really fascinating to hear what her team is doing then as with the advance over the rectal thermometer you need to get to a point where you can just put a thing on your skin and it just measures it and you don't even have to lose any blood over it at all right correct uh and yeah and taking like initially i i read one of the study where uh we were thinking that we can like it was a separate study but the point was that you can send a a home kid and they can just you know prick themselves and take the blood sample which is easier rather than asking someone to come into a lab and do it. So if we could do something like that, astronauts for sure would be, you know, well-trained to take their own blood sample. And you can use

that as a feedback to see how their circadian rhythm is in training or shifting in the desired direction. Is there anything else that you heard from Jean Duffy or Rosemary Braun that sparked any particular thoughts for you? Yeah, like right now, the models that I use for my research had only light as one of the stimulus. My current work is actually looking into how meal timing impacts it. Then maybe we can look into the content of the meal as well, like this research where they say you should have more carbs in the morning and more fats in the night that one of the profs she is working or she already has that model where they have integrated few different stimulus which is amazing and i would really want to look more into that so now we need the ai robot to not only be measuring you and seeing how

your sleep cycle is going and adjusting your light treatment accordingly, but also cooking you your meals and playing the violin to you at the right time or something like this, full service, circadian rhythm adjustments. Yeah, for sure. I think music could be really, like I haven't read much papers, but you know, when even you're feeling sleepy

and you start listening to a hip hop music, you obviously, you know, you feel very active. So music could be one of the stimulus so yeah we could definitely think of adding music to that list as well critica it's been fascinating hearing about your research thank you so much for all the time that you've spent with us oh thank you for taking time and listening about my work. Thank you so much. You were listening to Resetting the Body's Clocks,

featuring the work of Toronto Metropolitan University PhD graduate Kritika Vashisht. It's part of our ongoing series, Ideas from the Trenches, where we feature outstanding PhD research from across the country. This episode was produced by Tom Howell and Pauline Holdsworth. If you are working on a PhD and would like to be considered for Ideas in the Trenches, just email us through our website, cbc.ca slash ideas.

Thank you to all of our guests. Rosemary Brown. Jean Duffy. Bruce Pollack. Jamie Zeitzer. For more on our guests and their work, you can head to our website, cbc.ca slash ideas. Technical producer of Ideas is Danielle Duvalval our web producer is lisa ayuso acting senior producer is lisa godfrey greg kelly is the executive producer of ideas and i'm nala ayed For more CBC Podcasts, go to cbc.ca slash podcasts.