San Diego researchers unlock the key to what wakes us up helping us better understand our biological clock
October 3, 2011 1:30 p.m.
Dr. Satchidananda Panda, Biologist, Salk Institute
Related Story: San Diego Scientists Discover Gene That Wakes You Up
CAVANAUGH: This is KPBS Midday Edition. I'm Maureen Cavanaugh. If you are among the membership wake up a little bit before your alarm clock rings, have you ever wondered why? What is it that triggers us to wake up on our own? Researchers at Salk institute say they have found the gene that wakes us up. The reason that's important is that some chronic sleep disorders and diseases are linked to fragmented biological clocks. I'd like to welcome my guest, biologist doctor Satchidananda Panda who along with his research associate isolated the wake-up gene. The findings were published in this month's edition of the journal science. Thank you so much for coming in.
PANDA: Thank you, Maureen
CAVANAUGH: I'd like to invite our listeners to join this conversation. Do you wake up at the same time each day? Do you have perhaps an unusual sleep pattern? Give us a call with your questions and comments, that's 1-888-895-5727. Doctor Panda, this discovery helps us understand what mechanisms are in place to tell our body to wake up. But first, can you explain how our body clockworks?
PANDA: Yeah. For over the last 10 to 15 years, we got a very rough idea of how our body clockworks. There is one critical protein called PERIOD protein. What happens is, the PERIOD protein level goes up throughout the day. And in the evening, it comes down. So the body just looks at the number of proteins of this PERIOD protein in the cell and says, ha, this is morning or this is evening. So that's how the body clock kind of works.
CAVANAUGH: Ah, now, you say the human body is a collection of clocks. What do you mean by that?
PANDA: Yeah, so a very long time we thought that there is only one clock somewhere in the brain. And that it tells us time. A few years ago Na very surprising discovery, people found that almost every cell in our body has its own clock. For example, your liver as I clock, your skin has a clock, your eye has a clock, and all these clocks talk to each other. And they tell our body when to do what.
CAVANAUGH: Until now, it hasn't really been known how the body works when it's waking up.
PANDA: We took advantage of this idea that there's a clock everywhere. So we don't have to tile take a whole human or whole mouse and do this work. We can just take a little bit of cells from human skin or from mouse tail, and then ask what happens in these cells. And we monitor the PERIOD level was going up and down. And as they break, they're just stopping this -- and in the morning, something has to come, and take the brake off, and push the gas pedal. And we found this preteen just comes in the morning and takes off that brake and lets the PERIOD protein again begin to rise so that the body will know that this is morning, and we have to do different things throughout the day.
CAVANAUGH: And how is it that your body gets used to waking up as a certain time? I think is that many. Us will set our alarm because we're afraid we may over sleep, and yet I don't think I've heard my alarm go off in years. I mean, I kind of always wake up a little while before the alarm. And I thought I was alone in that. But from what I've heard you say, that's not the case at all.
PANDA: NO, actually our body has a remarkably accurate clock. And what is interesting, over years this body clock will set for example, for 24 and a half hours or something like that. Even if we take a little bit of cells from your skin and culture them, that clock in out cells will also work nearly 24 hours, day after day after day for many, many weeks. So it is really amazing to see that each of our cells has a very sophisticated Swiss watch already built into it.
CAVANAUGH: I'm speaking with doctor Satchidananda Panda, and he along with his research associate at the Salk institute have isolated the wake-up gene. Their findings are published in this month's edition of the journal science, and wee taking your calls at 1-888-895-5727. Meredith is on the line from Alpine. And good afternoon, Meredith. Thank you for calling.
NEW SPEAKER: Hi, good afternoon. Thanks for take Moog I question.
NEW SPEAKER: Hi. I want to know what I can do to change my gene. It wants to go off at three 30 in the morning. And it's been doing this for years, and I know a lot of other people, a male friend of mine recently told me that's been his problem as well. And sleep aids, they tend to keep him -- help you to fall asleep, but they don't help me to stay asleep.
CAVANAUGH: That's very interesting. Doctor?
PANDA: Yes, so that's a very interesting question. In terms of sleep problems, we essentially have three different type was sleep problem. One, people have difficulty falling asleep. Second, people go to sleep but they cannot stay asleep a long time. And third is in the morning, even after 8 hours of sleep, people wake up and feel like they didn't sleep last night. So we really don't know how the clock or which aspect of these three things is regulated by your clock. Because there are two different mechanisms that tells our body to sleep. One is if you're really too tired, then you will fall asleep. No matter what time of the day. If you really worked hard throughout the day, throughout the night, you will fall asleep in the morning. And it seems like the biological clock does not control that aspect. What it controls is when you go to sleep and then how many hours you stay asleep. From our discovery to actually finding a drug or something that will keep people asleep for a long time, that will take a few years.
CAVANAUGH: Right. I want to talk more about that. And I also want to talk about the illnesses that are connected with not being able to stay asleep or not being able to maintain this proper rhythm. But first I wanted to ask you if you heard about someone who basically said they could tell themselves what time they wanted to wake up in the morning. Would any of your research support that?
PANDA: NO, actually that's another mystery with that we still don't understand. Sometimes you might say, well, I have to get up at 4:00 to catch a flight, and you might get up. But we actually don't know how that works.
CAVANAUGH: That's beyond your current state of research.
CAVANAUGH: Okay. Tommy is calling from San Diego. I want to tell everyone again we're taking your calls at 1-888-895-5727. Hi Tommy, good afternoon. And welcome to Midday Edition.
NEW SPEAKER: I think the doctor kind of answered my question. My question was that it seems like every morning -- well, every night of every day, I always wake up around 2:00, 4:00, and 5:00, those are the hours I wake up, no matter how tired I am so I was just curious, I think you answered my question, but then I always wake up, typically wake up as well when it's time for me to wake up.
CAVANAUGH: Tommy, thank you for the call. Is that -- are you at a state of research where you can now say that that is a malfunction of the wake-up gene?
PANDA: Yeah, so as I said, every cell in our human body has a clock. But sleep-wake cycle is kind of at a good indicator of how hour clockworks. So usually when we have this fragmented sleep, that means there's something wrong with the clock, might be wrong with the clock. And that's showing up in our sleep-wake pattern. There might be something else wrong in the body and that we might not know for a very long time. And after a while, those kinds of malfunctions will show up as chronic diseases.
CAVANAUGH: As we age, there are variants in our body clock. I guess our sleeping patterns. Do we understand why that is, and is this discovery of yours going to be helpful in understanding why it is that age plays a factor in this?
PANDA: Yeah, so that's a very interesting question. And that's one of the reasons why we got into this. We know that as we age, our body clock becomes weaker and weaker and weaker. So that, for example, that PERIOD protein that I told you about, that PERIOD protein does not go all the way up during that time, and cannot come back all the way down. So the body gets confused in dealing out this period protein level and thinks it might not be the right time for the right thing. So the dampened clock essentially confuses our body. And another thing you also brought up early ones are is many shift workers who stay up late into the night after many, many weeks or years, their clock also becomes very weak. And their body cannot tell what time of the day it is. And what is interesting is when we mutate this gene, we found, we almost see a similar kind of pattern that we see in old people. When we mutated this gene in fruit flies, the fruit flies cannot go to sleep very well. They go to sleep and they, very a few hours, they get up as if they had a short nap, and then they eat a little bit and go back to sleep. So they do that throughout the day and night. When we put the gene back into the fly, they behaved almost like young fly, they had a good night's sleep, get up in the morning and go eat enough, and were very active. So far I think this vehicle protein that we found, this gene, will give us some clue about why our clock breaks down as we age. Or when we work into late night for many, many weeks or years.
CAVANAUGH: Let's take another call. Maria is calling from Vista. Hi Maria, welcome to the program.
NEW SPEAKER: Hi. Thanks for taking my call. The reason I'm calling is because I have a 21-year-old son who likes typically -- they don't keep regular sleep patterns. And I'm wondering, I've always suspected that this affects the immune system quite a bit. And he does have a lot of difficulty falling asleep because he never falls asleep at the same time. And as you were just talking with, he gets up and he'll eat at any time of the night because he's not sleeping. So just how bad is this for him? And how to really -- does it affect the immune system?
CAVANAUGH: Thank you very much for the call. How bad is it for health?
PANDA: Oh, see, actually you asked the right question. It's really bad for the health because what our clock does, it does more than just sleep. It tells our body when the immune system should be functioning and when it should take a rest. It tells the liver when to burn glucose, and when to burn fat. And it tells our kidneys to function properly. Our muscles, our heart, almost every single organ. And we know that when people age or in shift workers when the clock breaks down, people also become more susceptible to disease as their immune system is breaking down. They also have higher incidents of diabetes and obesity, and they have higher incidences of cancer. So we know the clock disruption correlates with break down of community, increased incidents of cancer and diabetes and obesity. And what and interesting about these particular discoveries, this particular gene we found is already shown to have a very interesting function in the immune system, in cancer, and also in metabolism or how our cells actually break down sugar. So that's why you're more excited that maybe this will give us a clue how clock controls all the things, and in older individuals or in shift workers, is this the gene that's disrupted? And if so, can we fix it to fix the clock and also prevent cancer, diabetes, and infectious disease?
CAVANAUGH: Where do you take -- because this is pure research?
CAVANAUGH: That you've done. So where does that go now? What is the next step in this chain to try to figure out more about how the body's natural clock actually operates?
PANDA: Yeah, so it's almost like, for example, if you have a car, and if your car doesn't start in the morning and the only thing you know is, well, maybe there is no gas in the tank. Then you will check that gas tank. And then there is gas. You have nothing else to check. Then now as you know, another thing that might have gone wrong, now we'll go back and ask in animals or fruit flies or possibly in human cells that don't have a functional clock or a clock, they'll ask, is this the mechanism that's broken down? That's one thing we can ask. Another thing, as I told you, this gene has already been linked to cancer. And you know that there are many kinds of cancers where this gene is mutated. And there is a connection between cancer and sleep pattern. Many cancer patients do not get a good night's sleep. Now we'll go to those cancer cell lines and then ask how is the clock functioning there? Can we actually fix this gene or bring a drug that will mimic its own function so in that way we can correct the clock and possibly see improvement in other diseases.
CAVANAUGH: What an exciting discovery. I have been speaking with doctor Satchidananda Panda of the Salk institute. I want to thank you and congratulations.
PANDA: Thank you, Maureen.