说话人 1: Welcome to the Salk Institute’s 治愈的起点 podcast. Where scientists talk about breakthrough discoveries with your hosts, Allie Akmal and Brittany Fair.
Brittany Fair: I am here with Dr. Emily Manoogian. Dr Manoogian is a postdoctoral fellow in the lab of Dr. Satchin Panda, where she studies chronobiology. So Dr. Manoogian, what is chronobiology?
Emily Manoogian: Great question. So chronobiology is really just studying the timing of biology. So chrono being time and then biology being biology. So, really just studying the timing of everything. Chronobiology, as a field, is very broad. It ranges from people studying many different model organisms. So, everything from a single cell bacteria to marine life, to mammals, to humans, everything has a circadian clock. I mean even plants, that’s actually a pretty big field. That’s where it was originally discovered.
Brittany Fair: So does this mean that everything in this world is on some kind of clock?
Emily Manoogian: As far as we know, the hypothesisis that every living thing has a clock. For a whileit was thought that extremophiles, these bacteria that can live in these super extreme environments that really don’t have daily rhythms in the environment, did not have rhythms. But even then there’s been some data to suggest they have different types of rhythms, but they do exist. And the ideas that we’ve all, all organisms have created a way to adjust to this 24 hour cycle in environmental changes. So it’s really a way of preparing your body for what it needs to do and anticipate what it needs. And so, regardless of what kind of organism you are, you still need to anticipate that environmental change.
Brittany Fair: And what do you mean by circadian clock?
Emily Manoogian: Yes, so circadian is just Latin for about a day. So circa is about, dian is day. That is one example of a biological rhythm. There are others obviously. So, we have circa annual rhythms. It would be a yearly rhythm. We have these now tidal rhythms. We have monthly rhythms. We even have ultradian rhythms, which are shorter than 24 hours. They’re still usually in factors that would multiply to 24 but not always. And as science is progressing, there’s been more and more studies show there might be these micro rhythms that then result in larger rhythms, so that these really short scale. So there’s many different kinds. Frequently you hear about circadian rhythms because that is that 24 hour oscillation that is really adapting to the environment. But those other rhythms are also very important and can be very insightful.
Brittany Fair: When you speak about circadian rhythms, it makes me think of the sleep wake cycle.
Emily Manoogian: Yeah. So sleep wake cycles is one example of a circadian output, right? So if we think about circadian behavior, sleep and activity is the easiest thing to relate to. Because we all sleep, we all get up. Generally we have a pattern to that, but there’s actually rhythms in all kinds of behaviors. So sleep is not the only one.
Brittany Fair: So what are some other examples?
Emily Manoogian: Yeah, so pretty much any behavior. So mood actually oscillates throughout the day.
Brittany Fair: Really?
Emily Manoogian: Even your cognitive ability oscillates throughout the day. In fact, there was a study I think that came out last year said they had 73 different personality traits that fluctuated across the day.
Brittany Fair: That’s fascinating.
Emily Manoogian: Most people tend to be the most cognitively able around 10 in the morning, depending on when you get up. It could be a little earlier or later on your own schedule. But morning is typically your most alert and cognitively able. There’s been some interesting things too anecdotally that people are best at editing things at night. And just your rational abilities change throughout the day. So there’s all kinds of things like that.When we think about more direct physiological behaviors aside from sleep wake, like when we eat, when we run, when we’re active. All those things or even social interactions, are we going to have a really intense conversation? All of those things are influenced by the clock and also feedback on the clock to give it cues about what time of day it is.
Brittany Fair: So do you try and schedule your meetings around 10:00 AM every day?
Emily Manoogian: No. I need my cognitive abilities for whatever’s happening then. And it depends on the person, right? There’s definitely different types of… Everyone has their own circadian clock. Everyone has a slightly different phase. So their relationship of my 10:00 AM, “10:00 AM,”my best cognitive performance is probably different than someone else’s. So it’s all relative. Even physically, you have your greatest muscle strength in the afternoon, but you have different skills at different times of day. So physically, mentally you’re really just a different person at different times of day.
Brittany Fair: I think that’s so interesting because I am currently training for a triathlon.
Emily Manoogian: Wow!
Brittany Fair: And I’ve heard that 4:00 PM is the best time to work out, but I had no idea why.
Emily Manoogian: Yeah, so you actually do have higher muscle strength. Again, I don’t like using exact clock hours, like time on a clock.
Brittany Fair: 好的。.
Emily Manoogian: Because if you’re a morning person and you wake up at 6:00 AM versus someone who wakes up at 10:00 AM, that 4:00 PM is a very different number for those people. But generally in the late afternoon is, you have your peak muscle performance. And it also changes your blood pressure. So depending on what you’re going for, you can push yourself in different ways at different times of day.
Brittany Fair: That’s very helpful to know. And how does the timing of when we eat affect our body?
Emily Manoogian: Now, light is the biggest cue to tell that clock in your brain the time of day that it is. And so light is super important to get right and is really the easiest way to reset behavior. Especially shown in animal models, but we also know it’s really potent in humans. The problem is is all those other clocks throughout your body are actually more sensitive to nutrient cues than they are to light. They’re only going to get that light cue downstream from the clock in your brain. But if you change nutrient availability, they respond instantly. And so food is a huge cue to pretty much all of your body to tell it this is the time of day that it is. If it’s eating, it’s assuming that it’s during your active phase. If you’re eating at the same time of day during your normal day time within a reasonable interval. It’s a great way to support your circadian system and say this is the time of day that it is. And it’s this positive feedback to say we’re on time. This is what’s going on. And it’s reinforcing that. When we eat super early or super late or in middle of the night, or just even high variability in the times that we eat, it’s really a very inconsistent queue, and it’s trying to reset the clock all the time. And then-
Brittany Fair: So how can we best biohack the system?
Emily Manoogian: Yeah, so that’s a great question. That’s what all of our research is focusing on right now. The big thing is obviously what you’re eating and how much you’re eating is absolutely important. Our line of research is, and many other people in the field have shown that when you eat is also really important. So there’s a few aspects to it. First is variability. So trying to have regular eating times, especially the first meal and the last meal. Try to be more regular. There is a good amount of evidence out there and I think it’s growing that having really variable, switching your breakfast time by more than an hour is associated with some negative consequences. So keeping it regular and that’s every day of the week, not just weekdays versus weekends.
Brittany Fair: Good to know.
Emily Manoogian: So there’s also a good amount of evidence saying to have most of your calories in the first half of your day. So having a really small breakfast or lunch and then binge eating a dinner has been associated with a lot of different health negative health consequences. So the whole saying of eat breakfast like a king, lunch like a prince, dinner like a pauper, I think actually might have some scientific backing to it. And our research suggests that eating, that duration should absolutely be shorter than 12 hours a day. When we do interventions we put people on a 10 hour duration. So for instance, 8:00 AM to 6:00 PM or 9:00 PM to 7:00 PM. And if you consolidate everything into that period, you’re allowing for two things. One, you’re giving your body those nutrient cues when you’re absolutely in your active phase and not when you’re about to fall asleep. Secondly, you’re allowing for a daily 14 hour fast. And sometimes people hear the word fasting and they go, ah, that’s an extreme thing. But no, it just means you’re not eating. You’re not taking in calories at that time. We think of the digestive system as a road. If you need to fill in potholes or realign things, you need to get the cars off the street and you need a chance to do that.
Brittany Fair: This sounds easy for someone like me who has basically a 9:00 to 5:00. But what about someone who does more shift work or someone who has an abnormal schedule like a flight attendant? How can they use this to their advantage?
Emily Manoogian: Great question. It absolutely depends on your schedule for how easy this would be to adopt. There’s some people that are like, “This is the easiest thing in the world. How can everyone not do this?” And there’s others it’s like, “Look, this is impossible.” We are currently working with the San Diego Fire Department to test out time restricted eating. But even there we have it a little bit easier than some because they’re on a 24 hour shift. So their day is still their day and they’re used to having most of their meals during the day and being active during the day. And although they’ll have to wake up and go on a call, they’re not usually staying up in between those calls. Unlike maybe a doctor or a nurse that would be on the night shift and they’re-
Brittany Fair: They’re actually working.
Emily Manoogian: … working the whole time that they’re awake at night. Or anyone that does night shifts. Right? Police, I mean I could go on.
Brittany Fair: 好的。.
Emily Manoogian: Shift work is extremely common unfortunately. I mean we need them, but it’s hard.
Brittany Fair: And you have a current study going on called My Circadian Clock.
Emily Manoogian: Yeah. So, My Circadian Clock is actually a tool that we use in a lot of studies. It is available worldwide for anyone to download.
Brittany Fair: Download, like on a phone?
Emily Manoogian: Yeah. So it is a smartphone App. It was developed in Satchin’s lab, but really it’s a tool for logging food. One of the problems is if you go back to all the traditional nutrition logging, it never included the timing of food. To get this data, the App locks in a timestamp, and then we can actually assess when are people taking in calories? When are you eating?The way it’s set up, it’s a two week baseline. What is your current lifestyle?We just want to know what is your eating pattern? And even if that’s all that you do that’s super interesting, because understanding eating pattern in different parts of the world is something that really needs to be done. And then after that you can set your own goals. So if you see that you have a 16 hour eating window, I wouldn’t jump to 10. I would say, “Okay, let’s go down to 12 or 14 even. Get your body comfortable there. Let’s go down to 11 or 12 now, and then maybe go down to 10 or 11.” If you’re interested in tracking your weight, then you can add everything that you’re eating, get that eating pattern in there and then update your weight frequently. If you’re interested in looking at how your blood pressure might change, you can add your blood pressure. In fact, you can add pretty much anything you’d get tested at a normal doctor’s office or a blood test. So you can keep track of things that are interesting to you. So if you’re interested in signing up for the My Circadian Clock App, you can visit us at www.mycircadianclock.orgg and you can sign up there.
Brittany Fair: I’m very curious to see where this research leads you. How long will you be collecting data from this App?
Emily Manoogian: We are planning on collecting data for a long time. We have a lot of collaborations going with experts in different fields that are interested in applying time restricted eating and understanding eating patterns in different ways. There is this really cool paper that just came out looking at where you are within a time zone, and the effect that that might have. If you’re on the west side of a time zone versus the east side of a time zone. And some very large countries like China don’t have different time zones, right? So people in different areas are getting much different exposure to light. And so when they eat, clock time, when they eat might be physically very different than someone else eating at that same time. We see similar things in Spain when, the light that they get is actually a bit delayed. So everyone says they eat so late and yes they do. Sure.
Emily Manoogian: But it’s actually not quite as extreme as you think when you adjust for the difference in the timing of light. So understanding that in many different ways. We need to keep the App going for a long time so we can get enough people to be able to analyze that properly.
Brittany Fair: Well, it’s just so fascinating too because I feel like we’ve always looked at what you eat, not when.
Emily Manoogian: I think it is important to note that many cultures that have fasting as part of their religion, there’s all kinds of different advice that we get from family members. And it really, if you go back to it, the Buddhist cultures had fasting periods. Hinduism has fasting. There’s Ramadan. I mean there’s all these different historical pieces of society that have influenced how we eat. I think now is the first time where it’s come from more of a basic science point of view. But we shouldn’t act like we’re the first ones to think of this ever because we’re not. It’s been part of human culture for hundreds of years. But now I think this is the first time we’re trying to analyze it in a scientific way. And do controlled clinical trials to find out what the optimal eating pattern is and really try to roll it out in a big way. And the fact that now we can do this kind of citizen science where we can put out an App that anyone in the world can use and collect data on really large scales, I mean that’s something that we can only do now because of technological advances.
Brittany Fair: Well, and also, I mean you’re not just looking at what time period is bad for you. You’re looking at what is the ideal time period? What keeps someone in health, which I think is an approach that people tend to not take. They really are looking at what goes wrong in disease. So that’s an interesting side to the story as well.
Emily Manoogian: Especially in the firefighter trial, it is more of a prevention as well. Is it something that’s feasible? Is it something that you can live with that it could potentially help you longterm? So I think this will be a very rapidly growing field. Even within the past year, the number of studies that have been posted on clinicaltrials.gov, I mean have just skyrocketed.
Brittany Fair: And what are some of the clinical implications for diseases such as obesity or diabetes?
Emily Manoogian: So those are the most exciting, I think. So I don’t see this as a weight loss diet. I see time restricted eating as part of what a healthy lifestyle mean. In the human trials that have been done, on average, time restricted eating leads somewhere between three and a half to five percent weight loss without people changing their diet. But what’s more exciting and where we actually see bigger differences is in some of these other cardio metabolic outputs. So we just finished a pilot study that’s under review right now where we had individuals do a 10 hour time restricted eating window for 12 weeks. And these were individuals that had metabolic syndrome. So they’re at high risk for diabetes, they’re at high risk for cardiovascular diseases. So they tend to have elevated cholesterol, elevated blood pressure, and they tend to be overweight. And some of them also have elevated glucose levels. And what we found is improvements across the board. So those that had elevated glucose before they started had significant decreases in their HbA1c, which is this average measure of glucose. And that was really exciting to see an improvement of that. And so we’re seeing these widespread cardio metabolic benefits and it’s not just us. Other groups that have tested 8 hour eating intervals and even a 6hour eating interval, which is a little extreme, but they’ve also shown similar improvements in glucose regulation and cardiovascular health.
Brittany Fair: How could this possibly be related to cancer?
Emily Manoogian: Yeah, cancer is interesting. Cancer cells can have different rhythms than your healthy cells.
Brittany Fair: No way.
Emily Manoogian: Yeah. So they can be out of phase with each other. So there are certain cancers where this is really effective, where if you can identify the phase of the cancer cell, and target that with chemotherapy while they’re dividing and your healthy cells aren’t, it can be much more effective and have very few side effects.
Brittany Fair: So I’m really interested in learning how you got into this field. I mean, were you always fascinated by circadian rhythms?
Emily Manoogian: No. I mean, who knows about circadian rhythms as a kid. When you’re five, you’re not like, “I’m going to be a chronobiologist.” And someone would be like, “What is that?”
Brittany Fair: Yeah. How did you even learn that chronobiology was a field?
Emily Manoogian: Was a thing. Yeah, I didn’t learn it until I was a sophomore in college and I took a class called Hormones and Behavior with Lance Kriegsfeld at UC Berkeley. Yeah, I fell in love with the class. It’s this big overlap actually between neuro endocrinologist and chronobiologist, because a big part of chronobiology is seasonal reproduction and how does this circa annual rhythm play into all these other things? And so that’s actually how I got interested in it. And I just loved the class. And then he had a second class called Biological Clocks and I took that. And that was how I got into chronobiology.
Brittany Fair: So what is your favorite part about being a chronobiologist?
Emily Manoogian: Oh, that’s good question. I think it’s just that it’s this kind of secret system that most people don’t really know about and it really affects everything. And it sounds like this really overstatement to say that chronobiology affects every other aspect of biology. But it’s very hard to find something that is separate from it. It’s like this core pillar of physiology that everyone ignores. Circadian system can be such a great supportive piece of health and it can also be very easily disrupted. And so I think it’s a really interesting intervention point where there are completely free noninvasive things that we can do. Like getting light at the right time of day, eating at the right time of day, trying to have regular sleeping patterns, exercising at the right time of day. That seem very simple and these little things, but can have really huge impacts on health. But I just think it’s this really beautifully intricate part of physiology that isn’t fully appreciated yet.
Brittany Fair: So do you have any advice for an aspiring chronobiologist?
Emily Manoogian: Do it? No, it’s a great field.
Brittany Fair: You can say do it but at the right time.
Emily Manoogian: Do it at the right time. No, now is actually a great time I think to join chronobiology. So, last year the Nobel prize went to a group of chronobiologists for the first time. It’s really expanded dramatically in the past 50 years. And so now is an amazing time to join the field because there is so much of a beautiful laid down structure. But there’s so much more to understand and it’s really not just a field of chronobiology, there are chronobiological aspects to any field, right? So it really is expanding into a lot of different things. The people within the field are really great and supportive. And so I’ve really enjoyed growing up within that field. And so I think it’s a good group to be a part of.
Brittany Fair: Well, thank you so much for being here today. It was fascinating to learn about the field of chronobiology and to learn more about your specific work in your current study.
Emily Manoogian: Yeah. Thank you so much for having me.
说话人 1: Join us next time for more cutting edge Salk science. At Salk, world renowned scientists work together to explore big, bold ideas from cancer to Alzheimer’s, aging to climate change. 治愈的起点 is a production of the Salk Institute’s Office of Communications.