Instant Genius - The body clock, with Prof Russell Foster

Episode Date: May 22, 2022

Neuroscientist Prof Russell Foster explains how our circadian rhythms control functions throughout our entire bodies. Once you’ve mastered the basics with Instant Genius, dive deeper with Instant Genius Extra, where you’ll find longer, richer discussions about the most exciting ideas in the world of science and technology. Only available on Apple Podcasts. Produced by the team behind BBC Science Focus Magazine. Visit our website: sciencefocus.com Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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So you can experience exceptional sound at home. Music just as the artist intended. Visit name audio.com to learn more. From BBC Science Focus magazine, this is Instant Genius, a bite-sized masterclass in podcast form. I'm Amy Barrett, editorial assistant at sciencefocus.com. Today I'm talking to Professor Russell Foster, a leading expert, on circadian neuroscience and the author of the newly published book, Lifetime, The New Science of

of the Body Clock and how it can revolutionise your sleep and health. He'll be speaking to me about our internal timekeeper and how it links to our daily experiences throughout the episode. First, I wonder if you could just tell me what actually is the body clock. Well, it's great to join you. I think you can think of the body clock as an internal, biological representation of a day, ticking away within the brain, which is, which contains the master clock, which then coordinates the rhythmic activity of essentially every cell in the body. I mean, if we think about what biology needs to do, it needs to deliver the right materials in the right concentration to the right tissues at the right time of day. And it's that

temporal structure in both space and time that the circadian system provides. And without it, essentially, everything falls into chaos. It's a bit like an orchestra. You've got sort of this this conductor in the brain, coordinating rhythmic activity. And then all the members of the orchestra scattered throughout the organs and the tissues of the body. And if they're all working together, if they're all sort of singing from the same hymn sheet, then you have a beautiful symphony. But of course, if they're all playing at a slightly different time, you have this, this cacophony. And so it's all about doing the right thing at the right time and fine-tuning our biology

to the very demands of the 24-hour revolution, of the earth on its axis and the dynamic changes that we see in light and temperature. So is it that there is one kind of location, one conductor somewhere in our brain that we can see on a scan and pinpoint that is our body clock? Well, that's how we used to think about it. We used to think that this structure deep within the brain in the hypothalamus called the supra-chiasmatic nuclei. It's a paired structure consisting of about 50,000 cells. And it sits in the brain where the optic nerves go into the the brain infuse and form what's called the optic chasm.

And it sits there and we thought, right, that's it. It's this driver forcing 24-hour rhythmicity onto every biological system throughout the body. And then what was discovered is that cells throughout the body, they were taken out. They were put in a dish and they showed 24-hour oscillations. And I remember when those data were first presented at a meeting and there was like an audible gasp. Because, you know, we come from thinking that the circadian rhythm was this network property of cell-cellar interaction to the realization that it's actually a subcellular molecular process, and that's contained within the suprachyasmatic nuclei. And then this revolution that every cell in the body is capable

of generating a circadian oscillation. So, yes, I mean, it's been a really exciting journey. I mean, my career has sort of spanned all these wonderful discoveries, which, we occasionally have been able to contribute to. And you mentioned kind of the word circadian. Can you just sort of tell me what that actually means? Yeah. So circadian means about a day. And this is a biological property.

And you define a circadian rhythm because the oscillation, the 24-hour change, whether it's in gene expression or electrical activity or indeed behavior, will continue under constant conditions. So the clock will continue to tick. So it's not a driven rhythm as a result of, for example, the change in light intensity at dawn and dusk. So that's one of its key properties. But it's no good having a clock unless it can be set to the external world. And so the second property is that it can be entrained or locked on to a cycle generated by the earth. And that's usually the light, dark cycle. And then the third property of a clock has to be that its temperature compensated, which means that despite huge,

changes in environmental temperature, the clock will continue to tick with a period of about 24 hours. If it didn't in, for example, insects or plants, it would mean that there would be no real biological time. And of course, this is what the clockmakers in the 17th and 18th century were trying to resolve a mechanical clock which continued to tick despite huge changes in external temperature. And of course, biology solved this billions of years ago. So this is something that it's not just in humans. Everything on the planet will have this. More or less.

And we used to think, oh, well, it's just multicellular organisms. And it's probably just sort of like vertebrates. And then, of course, actually, we knew that it was plants because one of the early observations by Demaria was on a plant. And he took mamosa plants. And these are the plants which, if you touch the leaves, they fold up. and he noticed that they would open and close. And he put these mamoza plants in a cupboard

and showed that under constant darkness, this opening and closing of the leaf would continue. And that was actually the first real demonstration of a rhythm that persisted under complete darkness. And so from plants and all the invertebrates, all the vertebrates, and we thought that, oh, it won't be bacteria, it won't be the prokaryants, because, you know, they're just too simple.

And, you know, lo and behold, a few years ago, yes, bacteria were shown to have circadian rhythms as well. So it seems to be almost a ubiquitous feature of life on Earth. In fact, looking for life on Mars, some of the experiments have involved looking for oscillations that are similar to the Martian Day, which is about 24 hours and 36 minutes or so. And so are hour clocks 24 hours on the dot? No, that's a great question, because in fact, on average, they're about 24 hours and 10 minutes or so. That's an average. And that's the more recent estimates, the early estimates, which are most often quoted in textbooks and things, is that the human clock is 25 hours.

That seems to have been a slight mistake. So, on average, they're 24 hours and 10 minutes. but some people are much longer and some people are much shorter. So there's a variation across the human species. Interestingly enough, we're quite variable as a species. If you look at mice or plants or whatever, they're much, much tighter. And one interesting question is, why do we have such a range of circadian periods? Periods?

Well, yes, the period is essentially the peak to trough change. and so our clocks are around about 24 hours and 10 minutes. So that's the oscillation. Whereas some people, their period could be in some extreme cases 26 hours or even 27 hours. And that's been associated, those very long clocks have been associated with changes in the molecular clockwork. Actually the machinery within the cell that makes the clock tick. So if it is sort of independent of light and dark, or it could be, could that mean that really, as humans, you know, we could just decide, or I could decide that I wanted to sleep during the day and work during the night and, you know, my body would adapt and my body clock would do that for me? No, absolutely not.

And I think that's the thing. I mean, the arrogance of being human and we're all the same, you know, we believe we can do whatever we like at whatever time of day. And of course, we have this temporal structure embedded within us, and you can't. And indeed, I remember, oh, good 20 years ago chatting to the chief, the head of the Confederation of British Industry. And he was saying, right, you know, we're going to solve the economic problems of the UK. We're going to run our whole industry on a 24-7 basis. So we won't have lots more buildings in London, and we won't have the Russia.

and he generally thought that the body clock would adapt to the demands of working at night, and it simply doesn't. 97% of night shift workers do not adapt to the demands of working at night. And that relates to the really very and fundamental importance of light in setting the clock. So, you know, the light, dark cycle sets this internal rhythm to the external world. and what happens for night shift workers is that they're under relatively dim light during the workplace. And then they experience bright light on the journey home or on the journey going into work. And the clock will always defer to the brighter light signal as being daytime.

And so the body clocks of night shift workers do not shift. So they're having to override this huge biological drive to saying, now you should be asleep, and yet they're essentially being forced to work. And to override this body clock, you have to activate the stress access, and what that does is essentially throw our biology out of kilter by forcing activity upon an entire biology which is prepared for sleep. So what impact does that have long term? Because obviously, you can understand sometimes I would stay up through the night

to finish a university assignment, but that was just a one-off, whereas people who are doing this for years, you know, even decades, what is that doing to them? Well, it's really interesting. So the World Health Organization has now classified night shift work as a probable carcinogen. And we should dig a bit deeper into some of the consequences of night shift work. Or just, you know, working out of kilter with our internal biology. So short term, there can be a big impact upon our emotional responses. So you see increased fluctuation in mood, irritability, anxiety, loss of empathy for failure to pick up those social signals from friends, family and one's work colleagues.

Loss of empathy, again, is a really interesting feature. Risk taking an impulsivity. I mean, doing stupid and unreflective things is a classic impact upon our emotions. There's a greater tendency to take stimulants such as caffeine or indeed something. less legal than caffeine, and then also to use alcohol as a sedative to wind down from these issues. Cognitive responses can be impaired, so the ability to multitask, the ability to multitask, memory consolidation really falls apart quickly, attention, concentration, that's something that really fails as a result of night shift work and disrupted sleep wake cycles, one's communication

skills, decision-making skills, all fall apart. So they're the relatively short-term effects that many of us have experienced as a result of working on those papers when we should have been a bit better prepared. But I think it's the more serious chronic impact that now has come to light. So daytime sleepiness and microsleeps are kind of obvious ones, but they're exaggerated by long-term night shift work. So for example, so recent study had shown that 57% of junior doctors had either had a crash or a near-miss on the journey home after the night shift. I mean, this is really serious stuff. Cardiovascular disease is very much associated with night shift work, altered stress responses. infection and lowered immunity.

I mean, one night of no sleep can reduce the effectiveness of natural killer cells by something of the order of 20 to 30 percent. I mean, quite, quite extraordinary. And of course, those natural killer cells are really important in preventing cancer spread, you know, identifying tumor cells. And, of course, you find higher rates of cancer. Very important studies on Danish night shift nurses showing higher rates. of colorectal cancer and breast cancer in that group.

And then we go back to that statement earlier, the World Health Organization saying that night shift work is now being classified as a probable carcinogen. Metabolic abnormalities, obesity, type 2 diabetes, very common in night shift workers compared to day shift workers. And of course, psychosis and depression. So mental health problems can be exacerbated by sleep weight disruption. So I think you raise a really important point because you just tend to think, oh, well, I'm just feeling tired at an inconvenient time.

But actually what we now know as a result of research over the past five to ten years is that circadian rhythm and sleep disruption impacts upon every domain of health. And that's why we need to take it so very seriously. And is this kind of risk just down to the sleep disruption element or are there other parts of the circadian rhythm? that, you know, perhaps we're not really thinking about when it comes to our daily cycles. Yeah, the problems in night shift work particularly are a misaligned clock. So we're trying to do things when the body is prepared to do something else. And the second thing is a cumulative loss and sleep disruption. And those are the two whammies that really hit a night shift work are very, very hard. Now, as I say, short term, so for many of us who sort of try and

throw that all-nighter, then we're working against an internal biology. We haven't got accumulated sleep debt at that stage. And of course, the number of years doing night shift work exaggerates the severity of these conditions. And you talked about variability in kind of our sort of times from 24 hours up to 27 hours. But what other kind of differences do, say, yourself or myself, what do we, you know, have different when it comes to our body clock. Yeah, I think it's a really fascinating question. And we're getting to the subject of one's chronotype, which is one's body clock type, and whether you're a morning person, an intermediate type, or a late person. And I think this is, it's a really very important point because we are very different.

We can have a huge range of chronotypes across the population. And one's chronotype, morning, intermediate or evening type is defined upon sort of three or four criteria. The first is one's genetics. So do you have changes in some of the fundamentally important clock genes, which either speed up or slow down the clock? And what's really extraordinary is that we now have examples where tiny changes in some of those genes and the proteins they encode will translate into whether you're a morning type or an evening type. I just think that's just so cool. It's in fact one of the examples we've got of how genes encoding their protein products ultimately change behavior. I mean, just one amino acid change can change morningness to eveningness.

Just so cool. The second is our development. So from about the age of 10, there's a tendency to want to go to bed later and later and later. Now, that peaks in our late teens, early 20s. And then there's a slow move to want to go to bed a little bit earlier and earlier and earlier. The time you're in your late 50s, early 60s, you're wanting to get up and go to bed at about the time you did when you were 10. And on average, that's about two hours earlier than when you were in your late teens at early 20s. So there's that change in development, but men and women

are different. Men tend to want to go to bed later for longer compared to women who peak in their sort of lateness earlier than men, and they never get on average as late as men. And in fact, it's only by the time we get to about 55, 60, that men and women, on average, are getting up and going to bed at about the same time, which I think is really intriguing. So there is that change. And that's probably due to the circulating levels of the sex hormones, estrogen, progesterone, and testosterone. So we've got our genetics, our development, whether we're male or female. But the fourth, which is so important, is how much morning versus evening light you see. Now, what we now know is that morning light will advance the clock. It will make you get up earlier

and go to get up and go to bed earlier, whereas evening light will make you go to bed later and get up later. Now, when we were all agricultural workers, and in 1800, we were all agricultural workers, basically, we got a symmetrical exposure to morning and evening light. And so we were nudged backwards and forwards, and so we stayed basically aligned. We did a study a few years ago on university students around the world, in Munich, in Oxford, in Perth, in Auckland. And the results were just amazing because it showed that the later the chronotype, the more of an owl you were, the more evening light versus morning light you've got. And of course, the evening light delays the clock, whereas the morning light advances the clock. So by just sampling one bit of the

light dark cycle can shift you either forward in time or back in time. It's a great problem for adolescents who struggle through the school week, then they massively oversleep at the weekends, missing the morning light, which would advance their body clocks, but they get the afternoon evening light, which then delays the clock. So it's that fascinating interaction, as with so many elements of our biology, of genes and the environment, which ultimately give us our body clock type. I don't mean to sound, you know, in any way offensive here. But chronotypes are one of those things that I think a lot of people may be associated,

because maybe it just sounds like a horoscope type thing. You know, it feels almost like it's one of those quizzes, you know, answer these five questions and we'll tell you whether you're a night out. You know, how do we know that this is, you know, not just sort of what we like to do and this is actually regulated? Yeah, yeah. So the questionnaires that have been developed to define whether you're a morning or evening type have been based and validated on real life recordings about when people actually get up and go to bed. and not only their activity, but also hormonal levels, because a one's avert activity can be masked. You can sort of set the alarm clock, and it'll make you get out of bed,

let's say at 7 o'clock every morning, but your underlying body clock might be different. So most of these surveys have had both an activity report, but also wear the hormones. And in particular, a hormone from the pineal called melatonin, which is very tightly coupled to the body clock. So if you know where the peak of melatonin is, whether it's advanced or delayed, you know where an individual's chronotype is, very accurately. In fact, we did some really interesting work a few years ago on looking at the rest activity cycles of individuals who are blind.

They have no eyes. And so they had no way of regulating their internal clock. So their clock was just drifting through time. And then we discovered this lady who's rest. activity was drifting through time, and then her husband, who was a long-distance lorry driver, would come home. And it looked as though her circadian rhythms then became aligned to her husband. And we thought, wow, it's not just light. There are other factors here. And then we also measured her melatonian rhythm. And what we found is, although she had set her alarm clock to get up and go to

bed at the same time as her husband. So her activity, her underlying circadian rhythms, her biology, was actually drifting through time. And so you have to be very careful about getting enough data to be sure about whether it's a genuine circadian rhythm or it's actually being driven by some external cycle. There are some things that are controlled by our circadian rhythms that, you know, we might not think. So things like fertility, you know, energy and even things. things like digestion, is that right? This is all controlled by this one big conductor. I think that's what I find so exciting is that it's all, you know, and because it kind of makes sense. We're doing this fine-tuning, delivering the right stuff at the right time,

to the right, you know, time of day. And so it makes sense that all of our biology is being time stamped to a greater or lesser extent. And absolutely. So where to start. I mean, let's start with metabolism. And so when we eat, we'll have a – when we eat, we'll influence the sort of thing that the body does with those calories. So when we're asleep, we're not taking in food. And, of course, to survive, we're mobilising stored calories to drive our metabolism. During the day, we're moving around.

We're taking in calories. And so we're using those calories as they're needed. But if you think about it, the metabolic status of somebody asleep and somebody awake is completely different. And so when we eat, will influence what happens to those calories. So if we eat, it's a very nice studies have looked at the same calorie intake, the same glucose intake across the day. During the first part of the day to the lunchtime, those calories are metabolized and used. was towards the late afternoon and evening, those calories tend to be stored as fat.

So individuals who were trying to diet were given the same set of calories and they concentrated those calories in the morning or lunchtime or lunchtime in the evening. They lost more weight when they were in the first part of the day and the second part of the day. And it kind of makes sense because that's what the metabolism is doing.

The really exciting new data as well is in the immune system. and so we now know that the immune system is turned up during the day when we're sort of likely to encounter pathogens from other people or moving around the environment and turned down at night. And this has been shown in a number of interesting cases. So it started as with most studies on mice. Mice were infected with a virus, either at the beginning of their activity phase or at the beginning of their sleep phase. given at the beginning of the sleep phase, more mice became sick and ill than if the virus

was given at the beginning of activity phase. And similar sorts of findings have been found in humans, not least, when to get vaccination. So there was a study a few years ago now looking at the influenza vaccine, either first thing in the morning or late in the afternoon, the virus, sorry, the vaccination that was given in the morning produced an antibody response threefold greater in the morning compared to the afternoon. And you could ask, well, hang on, why isn't the immune system on full throttle all the time? And of course, we don't know, but my thought about this was that if we turned up the immune system and it was aggressive all the time, we're more likely to trigger autoimmune responses.

So by concentrating the effectiveness at the immune system during the day, when we're most likely to encounter bacteria and viruses, we tune it up for then. And so we're both sort of saving resources, but also reducing the risk of an overly aggressive immune system that would trigger an autoimmune response. Now, I don't know, but these are the sorts of ideas that one can play with. The other thing that's so interesting, though, is that if you are getting sort of sleep and circadian rhythm disruption, then the effectiveness of a vaccine becomes much worse. Some very interesting studies compared individuals who were very sleep restricted,

only got four or five hours of sleep a night compared to what they would like, let's say, 7, 8, 9. and their immune responses were far less effective than the fully arrested individuals. All this raises some very important aspects, I think, for our frontline night shift workers, our nurses and doctors. So knowing that you're more vulnerable to infection at night means that the sort of protective coverings that you need, we should pay more attention to them, particularly at night. knowing that vaccination is less effective when you're asleep and circadian rhythm disrupted,

then we should make sure our frontline staff are fully rested before they shouldn't have done a string of night shifts, they'd become vaccinated, they should sort of be rested and then have their vaccination. And, of course, we need to work out, not least for COVID-19, when is the most effective time to deliver those vaccinations. So really interesting stuff, again, basic biology, you know, phenomenology, all that's cool stuff, but with an amazing translational potential. And so just a recap for anyone listening, what would you say the three things, three things that make the biggest difference to our body clock would be? Well, first of all, getting morning light, because morning light is critically important

in setting the internal day to the external world. And so that would be one key thing to do. And in terms of sleep, what time you sleep, how long you sleep, it's really important to appreciate that one shoe size doesn't fit all and that you as an individual need to work out for yourself what works best for you. And in a sense, so many people have become anxious by this stream of media saying you must do this, you must do that. And within that context, I'd be very wary of sleep apps. Now, sleep apps are great for telling you roughly when you went to sleep, how many times you work up in the night, and roughly when you finally work up.

But telling you you've had good sleep or deep sleep and all the rest of it, the algorithms just aren't good enough in most cases to give you that feedback. So rely upon yourself. Embrace the sleep that you get and don't get worried about. some of the stuff that's being told to you by a sleep app. It's worth bearing in mind that none of the Sleep Societies have endorsed any of the commercially available apps, and none of them, to my knowledge, are FDA approved as medical devices. So, you know, be aware, you're going to be different, and then try and work out for yourself. What's the best thing for you? So first of all,

morning light, which is really important at setting the internal day to the external day. The second, I would say would be careful about caffeinated drinks. They're really good at alerting us. And so I, for example, try not to drink any caffeinated drinks beyond 2 o'clock in the afternoon and certainly not close to bedtime. The other thing is that short-term use of sleeping tablets, fine, but it's really important to appreciate that sleeping tablets do not provide a biological mimic for sleep.

They essentially, they're sedatives. And so they can actually inhibit some of the really important things going on whilst we sleep. So again, short-term use, fine, but don't become dependent upon them. So there will be three things of many that one could embrace to improve one's sleep and one circadian timing. Thank you for listening to this episode of Instant Genius. That was Professor Russell Foster. If you want to know more about The Body Clock, check out his new book, Lifetime.

Or, to hear him tell me more about how we can manage our circadian rhythms, head over to Instant Genius Extra, available only on Apple Podcasts. The May issue of BBC Science Focus magazine is out now. Pick up a copy in store or visit sciencefocus.com. This podcast is sponsored by name, audio and focal. The texture and emotional depth of music can be lost through digital sources or podcast. signal. Name Audio believes you can have digital precision with analog warmth. Alongside French acoustic specialist vocal, Name creates high-end audio systems combining innovation with craftsmanship,

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