10/19/2018

How Genes Determine Our Quality Of Sleep

17:39 minutes

two men on a stage with microphones
Ketema Paul onstage with Ira Flatow. Credit: Brian Stethem

How did you sleep last night? If you’re one of the estimated one in three American adults who gets less than seven hours of sleep per night, you may not want to answer that one. As researchers cement the connection between sleep and health, others are still asking why some people have fewer problems sleeping, and others recover more easily from lost sleep. On top of that, there seem to be gender divides in who suffers from sleep disorders.

[What can salt production tell us about the ancient Mayan economy? Hint: A lot.]

In this interview recorded live in Thousand Oaks, California, UCLA associate professor Ketema Paul explains where our genes come into the picture and how they regulate our internal clock, sleep, and wakefulness. Plus, he’ll explain how his own work has found genes outside the brain—in skeletal muscle, of all places—contributing to sleep loss recovery.

Segment Guests

Ketema Paul

Ketema Paul is an associate professor of Integrative Biology and Physiology at the University of California-Los Angeles in Los Angeles, California.

Segment Transcript

IRA FLATO: This is Science Friday. I’m Ira Flatow coming to you from the Civic Arts Plaza in Thousand Oaks, California.

[APPLAUSE]

How did you sleep last night? Yeah, me neither. Something about being in the wrong time zone always catches me off guard. But I am not the only one, I can see from the audience. Statistics about sleep in the United States, among other countries, aren’t great. Fewer than two thirds of us are getting the recommended seven hours per night.

And you’ve probably heard by now that it’s a bad idea to consistently lose Z’s– chronic health problems, acute cognitive problems, the whole shebang. But is our ability to sleep more than just a product of our habits or schedules? Could there be genes at work? My next guest says the answer is yes.

He’s on the hunt for genes that regulate how well we sleep and how well we recover from lost sleep. And he’s found one of these genes in a surprising place nowhere near the brain. Welcome Dr. Ketema Paul, associate professor of integrative biology and physiology at the University of California, Los Angeles.

[APPLAUSE]

KETEMA PAUL: Thank you.

IRA FLATO: Is that right? You need to get seven hours of sleep a night. That’s what the usual requirement is?

KETEMA PAUL: Yes, for the majority of long-term studies that have looked, have found that if you get significantly less or significantly more than seven to 8.5 hours a night, then that doesn’t work out well for you in terms of–

IRA FLATO: I’m in a lot of trouble, yeah. Because I get like six. If I’m lucky, I get seven. I know someone who gets two hours a night and seems to be doing fine with that. But you’re saying that’s not–

KETEMA PAUL: Well–

IRA FLATO: Is that going to–

KETEMA PAUL: In all honesty, I’m in the six-hour crowd myself.

IRA FLATO: Why do we need to sleep in the first place?

KETEMA PAUL: That’s one of the biggest questions, actually, is why. It’s one of the reasons I have a job actually. What we do know is that if you don’t sleep adequately, that it impairs your health. So they’re kind of two categories of consequences if you’re not getting sufficient sleep every day. The first are what we consider short term. So many of you may stay up tonight after you leave here.

You may go hang out, to a party, or you just may be up with the kids, not get enough sleep. Tomorrow, your memory may not work as well. You may have a harder time focusing on things. You may make more errors when you try to do things that you normally do. Those tend to be cognitive effects.

There are more longer term effects, if you continue daily on a regular basis not getting enough sleep. Then there are health consequences. It impairs your immune system, which makes you at a higher risk for infectious diseases. And it also increases your risk for chronic diseases, like heart disease, stroke, and diabetes.

IRA FLATO: Now, I mentioned about genetics and sleep. What is there about genes? Are they involved in sleeping?

KETEMA PAUL: Interestingly enough, I think genes are pretty much involved in everything we do.

IRA FLATO: What about sleep would our genes control? Would it be the hour, the number of hours, the quality? What are the genes doing?

KETEMA PAUL: That’s what we’re trying to figure out. The interesting thing when you’re talking about genes is you’re not just talking about how genes are expressed, but you’re talking about how they interact with the environment. So I always like to point out the study of genetics is the study of genes and their expression, but also the study of the environment.

If you want to understand how genes work, then it’s a pretty smart idea to try to understand how the environment works. I’m from a kind of line of research that has shown that genes play an important role in timing sleep, the time of day you prefer to sleep, the time of day you prefer to wake up. But they also play an important role in consolidating sleep.

We are awake most of the day, we’re asleep most of the night. What we’re trying to understand are what genes are responsible for the restorative properties of sleep, the things about sleep that preserve your memory and your ability to focus, and the things about sleep that improve your health. The genes that regulate these aspects of sleep are still largely unknown. And that’s what my research is focused on.

IRA FLATO: Now what fascinated me about reading about your research also was that these genes that help with or control sleep are not in our brains. They’re not in our heads?

KETEMA PAUL: Well, they’re everywhere.

IRA FLATO: Yeah.

KETEMA PAUL: They’re expressed in the brain, they’re expressed in the body. The gene that I focused on in my most recent study, BMAL1 is expressed in the majority of tissues in which we have analyzed. So BMAL1 is what’s known as a clock gene. You have clocks in every cell in your body, very real clocks.

In order for something to be characterized as a clock, there has to be an input mechanism to set it. There has to be an endogenous timing mechanism, like gears. I talk to my students about gears on a clock. Most of them don’t know what clock gears are. So I talk about their electronic mechanism in their phones that keep time.

IRA FLATO: Right.

KETEMA PAUL: There’s an output mechanism that allows you to tell the time. The majority of cells in your body have these clocks. And we know that these clocks regulate sleep. For a long time, we’ve been very interested in how these clocks have regulated sleep, so we’ve looked primarily in the brain.

Because the clock that regulates most of your behavior is in the brain and most of the things that drive your sleep are in the brain. But what we found, quite surprisingly, was that the clocks in the skeletal muscle can speak to sleep regulatory areas in the brain and tell your brain how to sleep, and more importantly, how to recover from sleep loss.

IRA FLATO: What do you mean how to recover?

KETEMA PAUL: So the mechanism we study is sleep homeostasis. It kind of works like a thermostat. If you set a thermostat to a certain temperature, if it goes too low, turns the heat on, your thermostat turns the heat on. If it goes too high, your thermostat turns the air on. Your sleep processes work similar. There’s a certain amount of sleep that you need to function correctly every day.

If you don’t get enough sleep, your body will try to compensate by having you sleep more. If you get too much sleep, it will go in the other direction. The clock is the same as the clock on your thermostat. In the morning, it sets to go to one temperature. In the evening, it sets to go to another. It works the same way in our bodies. In the morning, your clock tells you to wake up. In the evening, your clock tells you to go to sleep.

For a long time, we’ve suspected that the clock mechanisms are more involved in the homeostatic mechanisms that allow you to recover from sleep loss. And what we’re finding in my research, and the research of many that have come before me, is that the genes, like the gears on the clock, the genes that are responsible for timing, also play a role in your ability to recover from sleep loss.

IRA FLATO: So when you say the clock, is that the circadian rhythm we’ve been talking about.

KETEMA PAUL: That’s the circadian clock that regulates your daily rhythms of behavior and physiology. So we have a 24-hour light-dark cycle. Sun comes up in the morning, goes down at night, synchronizes your clock. But if you were in a consistent lighting environment, constant darkness, or constant light, that clock would still continue to oscillate. It has an endogenous timing mechanism. And it would oscillate at a period or frequency close to 24 hours.

IRA FLATO: Question over here, yes?

AUDIENCE: I have a question about napping. As I’m getting older, I’m discovering that it’s a really cool thing to have a nap. How might that play with the clock that you’re speaking of in the cells?

KETEMA PAUL: So napping is a very interesting phenomenon, big fan of it, by the way.

IRA FLATO: Do you imbibe in it yourself, the nap?

KETEMA PAUL: I do.

IRA FLATO: OK.

KETEMA PAUL: One of the great things about being a sleep researcher is if I take a nap in my office in the afternoon, no one can complain.

IRA FLATO: You can write it off.

KETEMA PAUL: I know what I’m doing, this is research.

IRA FLATO: But you’re saying napping is important?

KETEMA PAUL: Napping is very important if you’re not getting daily sufficient sleep. And most of us that have children, or have jobs, or live in a busy environment may not be getting sufficient sleep. So if you’re not, then getting an afternoon nap, an hour is usually what’s about recommended, but anything from a half hour to an hour is healthy. However, if you are getting sufficient sleep and you’re still napping, that goes into hypersomnia, which is like I said, getting sleep too much.

IRA FLATO: Too much sleep.

KETEMA PAUL: And that suggests that there may be an issue. However, in relation to the clock, my lab is currently conducting studies to determine if the ideal time for napping is driven by clock mechanisms, especially those of us that get sleep here in the afternoons, sometimes between 1 and 3, which is currently the same time of a course I’m teaching right now.

IRA FLATO: Oh, gosh.

KETEMA PAUL: So I have to be pretty animated when I’m teaching.

IRA FLATO: But you can’t blame them either.

KETEMA PAUL: Exactly right. That’s why I don’t try. I understand, but that just means I have to work harder to keep them awake.

IRA FLATO: Let me go to the questions on this side, yes?

AUDIENCE: Hi, my question is about the adolescent brain and sleep. Ever since I was in high school, we were talking about shifting the start time for high schoolers to be later in the day because–

[CLAPPING]

Yes. And as a parent, I definitely want that to happen, because getting my kids up in the morning before noon is a challenge. So how does your study affect our decision making in forming our society in that arena?

KETEMA PAUL: So the quickest way to answer your question is that my study doesn’t affect that at all. But there’s a good reason for that. And the reason for that is because the science behind adolescent sleeping and timing, the fact that adolescent maturation is associated with a delay in circadian rhythms is well known, since I first came into this profession. But what you bring up is a great point about the ability of scientists to affect public policy. You know, I can keep you here for a very long time talking the mechanisms–

IRA FLATO: We’ve talked about this, yes.

KETEMA PAUL: –that drive adolescent sleep. But in answer to your question, there are very renowned researchers that have put forth myriad of evidence showing that delaying start times during adolescent maturation would improve the majority of outcomes in an educational environment. The trick is, how do you convince the policymakers?

IRA FLATO: Is there a gender difference in how people sleep.

KETEMA PAUL: So first of all, sleep is a complicated process. We like to think about sleep as we go home at night, we put our heads on the pillow, we wake up in the morning. But if you think about your entire life, and how you slept at different stages of your life, and how you’re going to sleep at different stages in your life, you recognize that sleep is a very complicated process.

For circadian timing, males throughout the lifespan tend to be a little bit delayed. But unfortunately, if you don’t have enough timing, then we can’t talk about it. Because one of the biggest issues with sex differences in sleep is that for the majority of the history of sleep research, women haven’t been included in studies, in clinical studies. Females, there’s been a small amount of females included in basic research studies.

So when you’re asking about sex differences, you’re asking about reproductive processes and how they occur during the lifespan. And quite frankly, since sleep has to be so dynamic, in women, who have to sleep during pregnancy, during postpartum recovery, during a menstrual cycle, during menopause, and the fact that we haven’t included cohorts of these women in the majority of clinical studies, we really are just unfortunately cracking open the egg of how women and men sleep differently over their lifespan.

IRA FLATO: I’m Ira Flatow. This is Science Friday from WNYC Studios. We’re here–

[APPLAUSE]

–yes– with Ketema Paul of UCLA. See if we have time for a couple more questions. Let’s go over this side.

AUDIENCE: Hi, thank you for your time. The question has to do with atypical sleep patterns and perhaps gene mutation. And is this studied, in terms of people who don’t have a typical sleep pattern, gene expression, gene mutation, and what impact that may have? Thank you.

KETEMA PAUL: Yes, on the majority of clinical studies. First of all, atypical is a word I try to avoid. I recognize its value. But what we’re beginning to recognize is that some of the gene– I talked about BMAL earlier, but some of its partners and the molecular clock that generates your rhythms have what we call polymorphisms, which are alleles, that are expressed in different members of the–

IRA FLATO: Little genetic pieces.

KETEMA PAUL: Exactly right. Or mutations that affect a variety of sleep characteristics. This is actually one of the most active areas of sleep research right now. So it goes back to the question you asked at the beginning, as to how much sleep is enough for each one of us. It’s only been in the past decade that we’ve identified these genetic mutations and how they encode sleep amount and a variety of other sleep traits.

So we’re really only beginning to understand whether the amount of time you sleep is genetically generated, if you’re predisposed to sleeping a certain amount of time, and if so, how the environment interacts with that predisposition. So in answer to your question, there are several labs that are investigating those areas right now. But we’re still at the beginning of answering those questions.

IRA FLATO: I have one final question for you. I’m what I would call a night person. I like to stay up late, go to bed late. I know there are a lot of people who are morning people. You know who you are out there, right? Is this a genetic thing too? Is there genetic, about going to bed late, staying up, going to bed early?

So this is something that we call chronotype.

IRA FLATO: Chrono type. And yes, it is to a large degree genetically regulated.

I’m a morning person.

IRA FLATO: We’re not getting along very well.

I tried to be–

[LAUGHTER]

I tried to do what Mark did earlier when I was a young person, but their inability to stay up late killed that side of the career. So now I’m in the lab. But yes, the very genes that regulate your chronotype, whether you’re a morning person or an evening person, are a lot of the genes that also determine a lot of your other sleep traits. So when we talked earlier about adolescence delaying as they mature, it’s those genes that regulate those mechanisms.

IRA FLATO: Is there any kind of blood test yet that tells us about our sleep needs, or what kind of sleeper we are, or deficiency?

KETEMA PAUL: Not yet, but I don’t think I would be exaggerating if I said that that would be, right now, among the holy grails of sleep research. That is–

IRA FLATO: A simple blood test.

A biomarker to determine whether you’ve sufficiently slept or not. If you can imagine when it comes to transportation errors and accidents, industrial accidents, accidents that occur in medical environments, the amount of errors that result from not getting adequate sleep, if there were some method for us to determine whether or not you’ve had adequate sleep, it would potentially lead to a dramatic reduction in errors, costs associated with those errors, and even lives.

Actually, many of the major funding agencies have set a priority in trying to pursue a biomarker or a blood test, sobriety test tends to be a word used, for sleep.

IRA FLATO: Fascinating. Thank you very much, Dr. Paul. Ketema Paul, associate professor of integrative biology and physiology at UCLA. Thank you for joining us.

Thank you also.

[APPLAUSE]

IRA FLATO: That’s about all the time we have. Our heartfelt thanks to Chris Kimball, Mary Olson, Duncan Lively, Andy Vasoyan, Lynda Fulford, Brian Stethem, and all the great folks at KCLU and California Lutheran University for hosting us.

[APPLAUSE]

And thanks also to Michael Cachco, Sean Jones, and all the amazing staff here at the Civic Arts Plaza for making this wonderful evening possible. And we want to thank our Science Friday staff. Takes a lot of people behind the scenes to run this ship. And let’s give one last round of applause for Money Mark, who’s going to play us out tonight. Thank you all for coming. In Thousand Oaks, California, I’m Ira Flatow. Drive safely and have a good night.

[MUSIC PLAYING]

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