Latest / What's Your Problem? / Every Cell in Your Body Has a Clock

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Every Cell in Your Body Has a Clock · What's Your Problem?

• 0:15
  Speaker 1: Pushkin Here's a thing I did not know until very recently.
• 0:24
  Speaker 1: Every cell in your body has a 24-hour clock in it.
• 0:28
  Speaker 1: In other words, your circadian rhythm is not just in
• 0:31
  Speaker 1: your brain, it is everywhere in your body. And it
• 0:35
  Speaker 1: doesn't just affect when you go to sleep and when
• 0:37
  Speaker 1: you wake up. It affects metabolism. It affects repair of
• 0:41
  Speaker 1: damaged cells. It affects the release of hormones. Your circadian
• 0:44
  Speaker 1: rhythm affects all kinds of things that need to happen
• 0:47
  Speaker 1: in your body to keep you healthy. Unfortunately, as you
• 0:52
  Speaker 1: get older, the clocks in your cells stop regulating everything
• 0:57
  Speaker 1: quite so well. The system gets disordered. Things fall apart.
• 1:02
  Speaker 1: It's not all bad news, though. There are things you
• 1:05
  Speaker 1: can do to slow the process of degradation. And scientists
• 1:09
  Speaker 1: are learning more. They are figuring out how to keep
• 1:12
  Speaker 1: the circadian rhythm in all your cells working better into
• 1:15
  Speaker 1: old age so that you can stay healthier for longer.
• 1:21
  Speaker 1: Music I'm Jacob Goldstein, and this is What's Your Problem?
• 1:32
  Speaker 1: My guest today is Karen Esser. She's the chair of
• 1:36
  Speaker 1: the Department of Physiology and Aging at the University of Florida,
• 1:40
  Speaker 1: and she's a world expert on circadian rhythm in muscle cells.
• 1:44
  Speaker 1: Karen's problem is this. What happens to the circadian rhythm
• 1:48
  Speaker 1: in muscle cells as we age? And how can we
• 1:51
  Speaker 1: keep the system from falling apart? Part of the answer
• 1:54
  Speaker 1: seems to be exercise. Exercise helps keep the circadian system
• 1:58
  Speaker 1: functioning better for longer. Now, in her research, Karen is
• 2:02
  Speaker 1: trying to figure out why. What is going on exactly
• 2:06
  Speaker 1: at the cellular level here? And the answer to that
• 2:09
  Speaker 1: question could shed light on other ways to fight age-related decline.
• 2:14
  Speaker 1: In our conversation, Karen and I discussed why muscle cells
• 2:17
  Speaker 1: need a 24-hour clock, what the circadian rhythm in muscle
• 2:22
  Speaker 1: cells means for when we should exercise, and Also, how
• 2:26
  Speaker 1: your stomach and your brain can wind up in different
• 2:29
  Speaker 1: time zones when you travel. And how Karen's research has
• 2:32
  Speaker 1: led her to change her own habits. To start, Karen
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  Speaker 1: told me that she didn't set out to study circadian rhythm.
• 2:39
  Speaker 1: She was actually looking at the effect of exercise on
• 2:42
  Speaker 1: muscle cells. And she wound up studying circadian rhythm because
• 2:46
  Speaker 1: of a finding that was so weird that at first
• 2:49
  Speaker 1: she thought it was a mistake.
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  Speaker 2: We were looking at responses in muscle cells. in response
• 2:54
  Speaker 2: to an exercise bout. And the clock genes came up.
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  Speaker 2: So that study, you know, 20 years ago was focused
• 3:00
  Speaker 2: on that with no idea of circadian clock genes.
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  Speaker 1: But you found it surprising. You said, oh, after a
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  Speaker 1: bout of exercise, these cells are turning on genes that
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  Speaker 1: we associate with the sleep-wake cycle, with the circadian rhythm.
• 3:14
  Speaker 1: And that was a surprise.
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  Speaker 2: Correct. But it's in the muscle. Yeah. What the heck?
• 3:17
  Speaker 1: So, like, why does the muscle care what time it is? And.
• 3:20
  Speaker 2: And really, is this just a technical problem? Did we
• 3:24
  Speaker 2: make a mistake? And so, you know, as a PI,
• 3:27
  Speaker 2: you always question your students first.
• 3:29
  Speaker 1: You thought somebody screwed up. You're like, there's no way.
• 3:32
  Speaker 2: No, no. And as usual, the students are fine and
• 3:35
  Speaker 2: they did the right thing. It's just the biology is
• 3:37
  Speaker 2: much more exciting. So that started my whole research trajectory
• 3:42
  Speaker 2: in that. So that's a little side note.
• 3:44
  Speaker 1: No, that's quite interesting. I mean, I think there's an
• 3:47
  Speaker 1: idea here. Let me take a stab at it. You
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  Speaker 1: can tell me if it makes any sense or if
• 3:52
  Speaker 1: I'm reaching. I feel like there's this interesting arc over
• 3:56
  Speaker 1: the past, I don't know, few decades, I guess, of
• 4:00
  Speaker 1: realizing that more is going on in each cell than
• 4:02
  Speaker 1: we thought. You know, I feel like there's this old
• 4:04
  Speaker 1: model where the brain is sort of all the action
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  Speaker 1: and then the body's just kind of dumb. The muscle just,
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  Speaker 1: you know, contracts and lifts things. But as we have
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  Speaker 1: looked closer, including the kind of research you're talking about,
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  Speaker 1: we've seen that, oh no, the cells themselves are talking
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  Speaker 1: to each other, are sort of Making what we might
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  Speaker 1: call decisions or, you know, adapting. And this seems like
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  Speaker 1: part of that, right? Like the fact that every cell
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  Speaker 1: has its own 24 hour clock is wild and really interesting.
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  Speaker 2: It is. It is. And I, you know, I'll be
• 4:33
  Speaker 2: real honest. When I first started, I had some colleagues
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  Speaker 2: that were like, what the heck are you doing? You know?
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  Speaker 2: Because I had my line of research, I had NIH funding,
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  Speaker 2: and now I'm going over it.
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  Speaker 1: You mean when you started looking into circadian rhythms in
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  Speaker 1: muscle cells? Yeah, because they just said, oh, it's.
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  Speaker 2: Just noise, or, oh, it's really, the muscle clock doesn't matter,
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  Speaker 2: it's just a dumb clock downstream of the brain.
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  Speaker 1: Well, why didn't you listen? Why didn't you think that?
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  Speaker 2: Well, I don't know, the whole thing fascinated me. The
• 5:02
  Speaker 2: idea that you have this clock that's an oscillator clock,
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  Speaker 2: regulating programs of gene expression in a cell. Yeah.
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  Speaker 1: And in a muscle cell, in a muscle cell, right?
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  Speaker 1: It's weird.
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  Speaker 2: Well, yes, yes. But again, I'm very influenced by evolution.
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  Speaker 2: Muscle cells are really.
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  Speaker 1: Old, okay? I mean, they're evolutionarily ancient, older than, say,
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  Speaker 1: eye cells or something like that.
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  Speaker 2: Or even a central nervous system, right? My whole training
• 5:30
  Speaker 2: and kind of how I've thought about biology... has been
• 5:33
  Speaker 2: more that muscle is part of this system. And so
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  Speaker 2: I think I was a little bit refractory to those
• 5:38
  Speaker 2: people that were concerned about me. Yeah.
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  Speaker 1: I mean, the idea that muscles are sending signals to
• 5:44
  Speaker 1: the body, right? That muscles are part of the endocrine system.
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  Speaker 1: Like they're not just there to move your arms and
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  Speaker 1: legs around. Right.
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  Speaker 2: Or look good when you're on the beach, right?
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  Speaker 1: Most importantly.
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  Speaker 2: So, right.
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  Speaker 1: So there is this broader... realization that, I mean, does
• 6:02
  Speaker 1: every cell have a clock, have a 24-hour clock?
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  Speaker 2: Virtually all cells. I think it's pretty safe to say yes.
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  Speaker 1: And other organisms? Like, does everything, does bacteria have a
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  Speaker 1: circadian rhythm? It does.
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  Speaker 2: I mean, they do. But, you know, I think, you know, plants, bugs, insects,
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  Speaker 2: you know, when you look across, you know, Almost everything
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  Speaker 2: you're looking at is going to have a clock in it.
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  Speaker 1: And like every cell in everything.
• 6:32
  Speaker 2: Yeah.
• 6:33
  Speaker 1: What is the clock? Like we're saying there's a clock.
• 6:35
  Speaker 1: It's not a clock. Like it's something where there's like
• 6:38
  Speaker 1: a 24-hour cycle where things change over the course of
• 6:41
  Speaker 1: 24 hours and they go back. But like what's going on?
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  Speaker 2: It's a great question. And as someone that sort of
• 6:47
  Speaker 2: came into the field from physiology, it took me, you know,
• 6:50
  Speaker 2: it took a little while to kind of wrap my
• 6:51
  Speaker 2: head about how to think about this. So there is
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  Speaker 2: what we call the core clock. And that is what
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  Speaker 2: I call the timer. So that's that 24-hour timer. And
• 7:02
  Speaker 2: so there is a process of gene expression. Then the
• 7:05
  Speaker 2: proteins are made and the proteins come back in. And
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  Speaker 2: then they do their function. And this takes approximately 24 hours.
• 7:13
  Speaker 1: Is the theory that mainly what it's doing is keeping time?
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  Speaker 1: Is there like a set of gene kind of expression
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  Speaker 1: and something happens and another gene is expressed and it
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  Speaker 1: takes 24 hours and that's its function?
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  Speaker 2: That's part of its function.
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  Speaker 1: Yeah. Like that is rad, right? Like that is such
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  Speaker 1: a wild evolutionary thing.
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  Speaker 2: Oh, it is awesome. And I mean, part of it
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  Speaker 2: is I just, like I said, I didn't train in this,
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  Speaker 2: but when I, the more I read about it, it
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  Speaker 2: was just like, holy, this is really cool. And, and,
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  Speaker 2: and it's what we call self-sustaining, which means it doesn't
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  Speaker 2: need a cue. You don't need light for it to work.
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  Speaker 2: You don't, it is intrinsic to that genetic network inside
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  Speaker 2: the nucleus of that cell. So it's frigging amazing. But
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  Speaker 2: it has another job, and this is important from a physiology,
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  Speaker 2: from an aging perspective, is that these core clock factors
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  Speaker 2: will also sit on lots of different places. So in
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  Speaker 2: muscle cells, they will sit on about 4,000 to 5,000
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  Speaker 2: different places across the genome in a muscle, and they'll
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  Speaker 2: help contribute to what I call a daily program of
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  Speaker 2: gene expression. And so I think of it as a
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  Speaker 2: temporal organizer of housekeeping. And again, for a muscle cell,
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  Speaker 2: What you see before you wake up in your muscle
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  Speaker 2: cells would be genes that are important for metabolism, right?
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  Speaker 2: For oxidative metabolism.
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  Speaker 1: So this is like early morning, an hour before I
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  Speaker 1: get up at whatever, 6.30 every day. What's going on?
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  Speaker 1: Let's do a day. Can we do a day in
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  Speaker 1: a muscle cell?
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  Speaker 2: We can do a day.
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  Speaker 1: Okay. So it's 5.30 in the morning, an hour before
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  Speaker 1: I'm going to get up. If it's a good night,
• 8:47
  Speaker 1: I sleep till 6.30. What's going on in my muscle
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  Speaker 1: cell at that time?
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  Speaker 2: So what the clock is doing at that time, so
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  Speaker 2: obviously your muscle cell is kind of hanging out, but
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  Speaker 2: the clock is regulating genes that are going to contribute
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  Speaker 2: to your ability to use carbohydrates and fats as fuel.
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  Speaker 1: So it's getting ready. It knows I'm going to get up.
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  Speaker 1: That's what's happening?
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  Speaker 2: Yeah, I think of it warming up the engine.
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  Speaker 1: I love it.
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  Speaker 2: The metabolic engine. So you get that warmed up because
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  Speaker 2: you don't want to start from cold.
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  Speaker 1: Okay.
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  Speaker 2: And so now you wake up and you're ready to go.
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  Speaker 2: And the things that are important so that, you know,
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  Speaker 2: your mitochondria are ready, all these things that are important
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  Speaker 2: for input or sensitivity to insulin or incoming glucose. They're already.
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  Speaker 1: So just to be clear, they're primed so that when
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  Speaker 1: I get up and I start using my muscles, whether
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  Speaker 1: it's just going downstairs to make breakfast or going for
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  Speaker 1: a jog, they're ready to take in sugar and make
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  Speaker 1: energy and do their work as muscles.
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  Speaker 2: Correct. Yes, exactly. So they're ready to do work because
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  Speaker 2: that's what muscles do. But they obviously need fuel for that.
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  Speaker 1: And then what happens over the course of the day?
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  Speaker 1: So now we're up. Is stuff changing all through the day?
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  Speaker 2: Absolutely. And so what you will see is that so
• 10:02
  Speaker 2: as you start moving, as you start working, depending on
• 10:05
  Speaker 2: how intense and that, some of your energy stores, like
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  Speaker 2: some of your... like glycogen, that will start declining.
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  Speaker 1: Yeah, which is basically stored sugar. Yeah, stored glucose.
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  Speaker 2: Right. So that's going to be highest in muscle at
• 10:17
  Speaker 2: the start of the day. And then it'll start to
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  Speaker 2: get used as you do things. Yeah. And then you
• 10:23
  Speaker 2: start moving into kind of the second half of the day.
• 10:26
  Speaker 2: And it's, again, depending on your daily life patterns, then
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  Speaker 2: it's starting to prepare for the rest phase, which means
• 10:33
  Speaker 2: what are you going to do during the rest phase? Well,
• 10:35
  Speaker 2: you're going to start restoring glycogen. You're going to store
• 10:38
  Speaker 2: other energy substrates. The way I think about it is,
• 10:42
  Speaker 2: you know, you don't want to be repairing and replacing
• 10:44
  Speaker 2: while you're using and contracting. I see. So you're going
• 10:47
  Speaker 2: to send that to the rest phase. Recovery and maintenance
• 10:50
  Speaker 2: gets done while you're in the shop, i.e. sleeping.
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  Speaker 1: Okay. So it's basically get ready to work, work, get
• 10:59
  Speaker 1: ready to recover, recover.
• 11:01
  Speaker 2: Correct.
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  Speaker 1: That's the basic cycle. Right. And so how does my
• 11:08
  Speaker 1: exercise habit affect the circadian rhythm? Oh, my God.
• 11:14
  Speaker 2: We don't have enough time for this one. Right. I'm sorry,
• 11:17
  Speaker 2: because we're just learning some really exciting things right now.
• 11:21
  Speaker 2: So this is a great topic.
• 11:22
  Speaker 1: Okay.
• 11:23
  Speaker 2: Because I also have this role within the Motorpack Consortium,
• 11:27
  Speaker 2: which is.
• 11:28
  Speaker 1: Love Motorpack. Molecular transducers of physical activity. Did I get it?
• 11:33
  Speaker 1: I don't have it in front of me.
• 11:34
  Speaker 2: Exactly. So what is it about exercise that makes us healthy?
• 11:37
  Speaker 1: Let's just say what Motorpack is, because it's part of
• 11:40
  Speaker 1: the reason I want to be doing these interviews, right?
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  Speaker 1: The big idea of like... We've known for a long
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  Speaker 1: time that exercise is really good for you, but we
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  Speaker 1: haven't really understood why at a kind of cellular level.
• 11:52
  Speaker 1: And motor pack is this big study trying to figure
• 11:55
  Speaker 1: that out, right?
• 11:56
  Speaker 2: Right. And I was part of the preclinical arm of
• 11:59
  Speaker 2: motor pack. So we worked with the animal stuff. And
• 12:02
  Speaker 2: what I love, I will say is, you know, we
• 12:04
  Speaker 2: studied 18 tissues in these animals. So we're looking at spleen.
• 12:08
  Speaker 2: We're looking at small intestine, different parts of the brain.
• 12:11
  Speaker 2: Not the usual suspects, the muscle, heart, you know, fat.
• 12:15
  Speaker 2: So anyway, so we are currently working on a series
• 12:18
  Speaker 2: of manuscripts to be submitted hopefully in the next six months. But,
• 12:22
  Speaker 2: you know, in terms of the systemic effects of exercise
• 12:25
  Speaker 2: and the way exercise or physical activity, if people don't
• 12:29
  Speaker 2: even want to just move, the way that can communicate
• 12:33
  Speaker 2: throughout your body to cells that you maybe didn't even realize,
• 12:36
  Speaker 2: you know, cells in the lung, your immune cells, like
• 12:40
  Speaker 2: I said, the spleen, The colon, the colon, you know,
• 12:43
  Speaker 2: with training, the colon is changing as much as a
• 12:45
  Speaker 2: muscle cell is. And so, you know, the health benefits
• 12:49
  Speaker 2: are absolutely systemic.
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  Speaker 1: I'm glad to hear it. Tell me about what you're
• 12:55
  Speaker 1: learning about the circadian rhythm in particular. And I mean,
• 12:57
  Speaker 1: really what I'm asking, so you've talked about the kind
• 13:00
  Speaker 1: of basic circadian rhythm. And so I'm curious, how does
• 13:03
  Speaker 1: it change with age? And how does it change with exercise?
• 13:07
  Speaker 1: And then what is the relationship of exercise and aging
• 13:09
  Speaker 1: in the context of the circadian rhythm?
• 13:11
  Speaker 2: Okay, so let's start with aging. So what we've done, again,
• 13:16
  Speaker 2: this is all with preclinical work, but the limited clinical
• 13:20
  Speaker 2: data with aging and circadian rhythms is very consistent. And
• 13:24
  Speaker 2: that is the clock works as we get older. So
• 13:27
  Speaker 2: the timer still works. So if you think about those
• 13:29
  Speaker 2: two functions I talked about, which is the timer, and
• 13:32
  Speaker 2: then we're going to call it the output of the clock,
• 13:35
  Speaker 2: the output changes. And the output starts changing in middle age, unfortunately.
• 13:41
  Speaker 2: So even though the clock's working, the types of genes
• 13:44
  Speaker 2: it's regulating and when it's regulating those genes... Going back
• 13:48
  Speaker 2: to your conversation with one of the other guests you
• 13:51
  Speaker 2: had on was talking about autophagy or the ability of
• 13:55
  Speaker 2: the cell to break down proteins. Well, at a young
• 13:58
  Speaker 2: age in the muscle, genes involved in autophagy are under
• 14:03
  Speaker 2: circadian control, and they are peaking just as we go
• 14:06
  Speaker 2: into the rest phase, as we were talking about. Right.
• 14:09
  Speaker 1: This is part of the sort of cleaning up the cells. Correct.
• 14:14
  Speaker 2: By the time the animals are middle age, those genes
• 14:16
  Speaker 2: involved in autophagy are now peaking toward the end of
• 14:20
  Speaker 2: the rest phase. So now they're going to be coming
• 14:23
  Speaker 2: on at a time you're going to want to be
• 14:25
  Speaker 2: moving around. And so, you know, when I think about
• 14:27
  Speaker 2: the clock, it's like you've disordered the sequence.
• 14:31
  Speaker 1: It's not working as well. It's going to work, but.
• 14:34
  Speaker 2: It's not going to work as well. The efficiency is
• 14:36
  Speaker 2: going to be down and there are going to be
• 14:38
  Speaker 2: more mistakes made. Yeah.
• 14:40
  Speaker 1: Okay. Okay.
• 14:41
  Speaker 2: And so then by the time you get to really
• 14:43
  Speaker 2: old age, it's just, it's awful. It really is. When
• 14:48
  Speaker 2: you're younger and even when you're middle age, there are
• 14:52
  Speaker 2: categories of genes that are regulated across all 24 hours.
• 14:55
  Speaker 2: By the time you get to, in the mouse muscle,
• 14:58
  Speaker 2: by the time you get to old age, that gets lost.
• 15:01
  Speaker 2: You get a peak of genes peaking around sort of
• 15:03
  Speaker 2: rest to active phase transition. But that's it. And the overlap,
• 15:09
  Speaker 2: So the genes that are what we call clock-controlled in
• 15:13
  Speaker 2: the very old are not at all what you see
• 15:15
  Speaker 2: in the younger animal, and they're not at all what
• 15:18
  Speaker 2: you see in the middle age. So there's a loss
• 15:20
  Speaker 2: of identity as well as a loss of timing.
• 15:26
  Speaker 1: We'll be back in a minute with some good news.
• 15:38
  Speaker 1: Tell me about exercise and circadian rhythms. You know, in
• 15:42
  Speaker 1: the muscle, but throughout the body. Like, what does it do?
• 15:45
  Speaker 1: How does it work?
• 15:46
  Speaker 2: So, we're learning. So, again, I always, I don't want to.
• 15:49
  Speaker 1: Well, tell me what's clear. Like, let's start with what's
• 15:52
  Speaker 1: most clear and then move towards sort of the frontier
• 15:54
  Speaker 1: of what you're figuring out.
• 15:56
  Speaker 2: So, what we do know is that muscle contractions or
• 15:59
  Speaker 2: exercise of the muscle absolutely talks with the clock system
• 16:04
  Speaker 2: in the muscle. And so... What that means is, let's
• 16:08
  Speaker 2: say I've been exercising in the afternoon and my work
• 16:11
  Speaker 2: schedule changed, so now I'm going to have to exercise
• 16:14
  Speaker 2: in the morning because of my job, right? So I'm
• 16:16
  Speaker 2: going to start exercising in the morning. What will happen
• 16:19
  Speaker 2: is the clocks in the muscles, it may not feel
• 16:21
  Speaker 2: great at first, but the muscle clocks will sense the
• 16:24
  Speaker 2: timing of exercise and they're going to shift. And in general,
• 16:28
  Speaker 2: the way to think about it is, so if I
• 16:29
  Speaker 2: was exercising in the afternoon, they're going to shift closer
• 16:34
  Speaker 2: to align itself with when, you know, I am exercising
• 16:38
  Speaker 2: in the morning. So that will happen. It doesn't require
• 16:41
  Speaker 2: a change in the brain for that shift to happen.
• 16:43
  Speaker 1: And so what is what's actually happening when that happens?
• 16:47
  Speaker 1: It's sort of like they're storing energy. Like, what does
• 16:50
  Speaker 1: that mean in practice, that shift?
• 16:52
  Speaker 2: What we would predict is that, you know, so all
• 16:54
  Speaker 2: the things I talked to you about, what happens to
• 16:56
  Speaker 2: your muscle over time a day, All you're doing is
• 16:59
  Speaker 2: shifting all those jobs to an earlier time. So you're
• 17:02
  Speaker 2: going to prepare for your activity earlier and then the
• 17:05
  Speaker 2: recovery will also be shifted in time. So you're going
• 17:08
  Speaker 2: to just take your biology and shift it over.
• 17:11
  Speaker 1: I mean, obviously, I know the main thing with exercise
• 17:14
  Speaker 1: is just exercise. And like, I'm not really an optimizer.
• 17:17
  Speaker 1: I just want to exercise every day. But, like, what
• 17:21
  Speaker 1: is what you're saying about the circadian rhythm and your
• 17:25
  Speaker 1: body adjusting if you usually exercise at a certain time? Like,
• 17:28
  Speaker 1: what does that mean for how I should think about
• 17:30
  Speaker 1: when I exercise if I have some control over when
• 17:33
  Speaker 1: I exercise?
• 17:34
  Speaker 2: So, I mean, this is a great question. What I
• 17:37
  Speaker 2: would say is if you're thinking about performance, like, let's
• 17:41
  Speaker 2: say you're going to be in a race or you're
• 17:43
  Speaker 2: going to then you want to be exercising about the
• 17:46
  Speaker 2: time you're going to be performing. So your system is
• 17:49
  Speaker 2: I really don't believe in optimization, but it's best suited
• 17:53
  Speaker 2: for that time.
• 17:54
  Speaker 1: Yeah, if you want to run as fast as you
• 17:55
  Speaker 1: can in your half marathon, then you should try and
• 17:58
  Speaker 1: do your daily jog at the time the half marathon's
• 18:00
  Speaker 1: going to be. Correct, correct.
• 18:01
  Speaker 2: If you're, you know, exercising for health, that's more important
• 18:05
  Speaker 2: than exactly when you exercise. And again, I also don't
• 18:08
  Speaker 2: want to be too overly precise. You know, the clock
• 18:11
  Speaker 2: is not, oh, you've got 15 minutes. If you don't
• 18:13
  Speaker 2: exercise now, you're not going to capture it. No, it's
• 18:16
  Speaker 2: not like that.
• 18:17
  Speaker 1: So you've talked about aging and the circadian rhythm. And
• 18:21
  Speaker 1: basically the circadian rhythm, just the clocks are not as
• 18:24
  Speaker 1: effective at doing what they're supposed to do as you
• 18:27
  Speaker 1: get older. And then exercise basically can adjust the clock.
• 18:33
  Speaker 1: What effect does exercise have on aging in the context
• 18:37
  Speaker 1: of circadian rhythm?
• 18:39
  Speaker 2: So a junior faculty member in my lab has a
• 18:41
  Speaker 2: study on that right now, and it's very exciting.
• 18:44
  Speaker 1: So it's a secret? Can you tell me?
• 18:46
  Speaker 2: Well, it's, you know, it's his work and I want
• 18:48
  Speaker 2: to let him But it's good. It's very good. And
• 18:52
  Speaker 2: so being more active improves the function of the clock
• 18:57
  Speaker 2: and the clock output. And this was data looking at
• 19:00
  Speaker 2: both muscle and liver. So the impact of exercise on
• 19:03
  Speaker 2: the clock is system-wide. It's hippocampus, hypothalamus, cortex, spleen, small intestine, colon, muscle, heart,
• 19:14
  Speaker 2: the usual suspects. But every organ in the body is
• 19:18
  Speaker 2: responding to exercise in terms of their clock components. And
• 19:23
  Speaker 2: so I am beginning to, well, I've been wondering about this,
• 19:26
  Speaker 2: but I'm beginning to think about exercise as a clock
• 19:29
  Speaker 2: improver with age. People are looking for small molecules. So
• 19:34
  Speaker 2: there definitely are people out there looking to target the clock.
• 19:38
  Speaker 1: Small molecules meaning drugs. Small molecules meaning drugs. Or nutraceuticals. Yeah,
• 19:42
  Speaker 1: or supplements. Yeah. And so, I mean, as I understood
• 19:46
  Speaker 1: it before, the problem isn't that the clock itself, it
• 19:51
  Speaker 1: still keeps time just as well, but that it's like
• 19:53
  Speaker 1: when the clock is telling other, well, genes basically, right,
• 19:57
  Speaker 1: to turn on or off, that's the problem. part that
• 19:59
  Speaker 1: gets less effective with age. Right.
• 20:01
  Speaker 2: Correct.
• 20:02
  Speaker 1: And so the intervention isn't to make the 24 hour
• 20:04
  Speaker 1: thing work, keep time better. It's the relationship between the
• 20:08
  Speaker 1: clock and all the genes it's turning on and off.
• 20:11
  Speaker 2: Perfect. You've got it.
• 20:12
  Speaker 1: Does it matter what time of day I exercise? Let's stipulate.
• 20:16
  Speaker 1: Always it's better to exercise than to not exercise. And
• 20:19
  Speaker 1: the important thing is to exercise. And, like, I'm not
• 20:21
  Speaker 1: trying to win a race. Like, if I have some flexibility,
• 20:25
  Speaker 1: does it matter?
• 20:26
  Speaker 2: I don't think so.
• 20:27
  Speaker 1: Is it better if I do it at the same
• 20:29
  Speaker 1: time every day if I can't?
• 20:30
  Speaker 2: That's what I'm going to come back to. I would
• 20:33
  Speaker 2: say that, you know, so what we do know is
• 20:34
  Speaker 2: what time you exercise can make things shift.
• 20:37
  Speaker 1: Yeah.
• 20:37
  Speaker 2: So probably what's not recommended is, you know— seven in
• 20:41
  Speaker 2: the morning one day and seven at night the next day.
• 20:43
  Speaker 2: And this is a new field, to be honest with you.
• 20:46
  Speaker 2: And so based on what I understand with the clocks,
• 20:50
  Speaker 2: with the clocks and exercise and health, I think just
• 20:54
  Speaker 2: find a routine that works for you. When you're active,
• 20:57
  Speaker 2: how you're active, if you're active, is going to be
• 21:00
  Speaker 2: an important informing cue for the clocks across the body.
• 21:06
  Speaker 2: And that's going to be important for health. And especially
• 21:11
  Speaker 2: with age, one of the key issues with aging is
• 21:14
  Speaker 2: a loss of resiliency. So you're exposed, you get a disease,
• 21:18
  Speaker 2: the disease progresses either more quickly or more seriously, so
• 21:22
  Speaker 2: you end up in the hospital. And it just leads
• 21:26
  Speaker 2: to a bad sequence. And to me, this is something
• 21:29
  Speaker 2: that addressing... clock robustness throughout the system is a way
• 21:35
  Speaker 2: we can help.
• 21:36
  Speaker 1: Why? Like what's the relationship between the circadian rhythm and,
• 21:40
  Speaker 1: you know, getting more or less sick if you get
• 21:42
  Speaker 1: an infection?
• 21:44
  Speaker 2: So if I think of, you know, my cell and
• 21:47
  Speaker 2: the ability of my cell and my cell's going to
• 21:49
  Speaker 2: get immune challenges, it's going to get all these things.
• 21:53
  Speaker 2: And you just think of it as this little island
• 21:55
  Speaker 2: that has to resist outside warriors. And so the clock
• 21:58
  Speaker 2: is a key part of the ability for that cell
• 22:01
  Speaker 2: or that tissue or that human to maintain homeostasis.
• 22:04
  Speaker 1: To stay healthy.
• 22:06
  Speaker 2: To stay healthy. And so what that also means, and
• 22:10
  Speaker 2: I will speak from my own aging perspective, is when
• 22:13
  Speaker 2: you get older, it takes longer to recover.
• 22:15
  Speaker 1: Yeah.
• 22:16
  Speaker 2: But the better you can keep your clocks working, the
• 22:19
  Speaker 2: more resilient your cells are going to be, the more
• 22:23
  Speaker 2: able they are to recover and to be strong and
• 22:28
  Speaker 2: resilient against external challenges.
• 22:30
  Speaker 1: I mean, does this go back to the idea of
• 22:32
  Speaker 1: like there's a time for resting and the time for
• 22:35
  Speaker 1: resting is sort of rebuilding, cleaning up? doing these things
• 22:39
  Speaker 1: that take energy and that we don't want to do
• 22:41
  Speaker 1: when we're moving around because we need our energy for
• 22:43
  Speaker 1: moving around. And when we're young, that just happens. And
• 22:46
  Speaker 1: as we get older, that works worse, but exercising makes
• 22:50
  Speaker 1: it work better. Is that the basic model?
• 22:52
  Speaker 2: Yes, that's the basic model. Yep, exactly. I think identifying
• 22:57
  Speaker 2: the experiments and the ways to demonstrate that very clearly
• 23:01
  Speaker 2: and directly is sort of where I'm very interested right now.
• 23:05
  Speaker 1: And does the kind of exercise matter in terms of.
• 23:08
  Speaker 2: I don't think so.
• 23:10
  Speaker 1: Yeah. Like resistance training, cardio, fast, you know, fast cardio,
• 23:14
  Speaker 1: slow cardio, whatever, just do whatever and it's good?
• 23:17
  Speaker 2: I think so. I mean, for the clocks, okay? I mean, obviously,
• 23:21
  Speaker 2: if you want to grow muscle, that's versus.
• 23:23
  Speaker 1: No, no, but for the clocks, yeah.
• 23:24
  Speaker 2: For the clocks, I don't think it's going to matter.
• 23:27
  Speaker 1: Great. I love that answer. Just do something. Don't do nothing.
• 23:31
  Speaker 2: Something. Yes. Yes.
• 23:33
  Speaker 1: You know, we got to talk about jet lag at
• 23:35
  Speaker 1: some point. I'm talking here to an expert in circadian rhythm.
• 23:38
  Speaker 1: How could I not ask you about jet lag? So
• 23:42
  Speaker 1: what should I know about jet lag? Tell me about
• 23:43
  Speaker 1: jet lag.
• 23:44
  Speaker 2: So what is jet lag? Jet lag is when you
• 23:46
  Speaker 2: travel to. So let's say I go from Gainesville, Florida,
• 23:50
  Speaker 2: to Paris, France. It's a six hour difference. And jet lag,
• 23:53
  Speaker 2: you feel crummy.
• 23:55
  Speaker 1: Not great. Right.
• 23:56
  Speaker 2: Right. That's a circadian syndrome. Yeah. Because all the clocks
• 24:00
  Speaker 2: in your body get disrupted by that change in light
• 24:03
  Speaker 2: cycle and that time cycle, and you feel crummy while
• 24:07
  Speaker 2: things are out of alignment.
• 24:08
  Speaker 1: Okay?
• 24:09
  Speaker 2: Until they all get aligned.
• 24:11
  Speaker 1: Well, and so there's two kinds of alignment, right? The
• 24:13
  Speaker 1: sort of vernacular alignment, the one I think of is, oh,
• 24:17
  Speaker 1: my body thinks it's whatever. six at night, but it's
• 24:21
  Speaker 1: actually midnight. But there's another kind of alignment given that
• 24:25
  Speaker 1: we have clocks in all of our different cells. Like
• 24:29
  Speaker 1: when you get jet lag, do your different cells wind
• 24:32
  Speaker 1: up thinking it's a different time within your body?
• 24:35
  Speaker 2: Yes. Different cells in your body adjust to the new
• 24:38
  Speaker 2: time at different rates. So you're going to be in
• 24:41
  Speaker 2: that period of blah. Yeah. your brain's going to adjust
• 24:44
  Speaker 2: pretty fast with the light cue. But the rest of
• 24:47
  Speaker 2: the cells, like your stomach and do you feel hungry or,
• 24:50
  Speaker 2: you know, whatever, I mean, they take different periods of
• 24:54
  Speaker 2: time to adjust.
• 24:55
  Speaker 1: So even just like shifting when you sleep to, you know, whatever,
• 24:59
  Speaker 1: I'm going to go to sleep in the middle of
• 25:00
  Speaker 1: the night and wake up in the morning, you're still
• 25:01
  Speaker 1: not going to feel good because your body is going
• 25:04
  Speaker 1: to be internally inconsistent. Your stomach's going to think it's
• 25:09
  Speaker 1: one time and your brain's going to think it's another.
• 25:10
  Speaker 2: Yeah, exactly. So when I think about alignment, I'm talking
• 25:13
  Speaker 2: about the alignment of the clocks in my brain, you know, heart,
• 25:18
  Speaker 2: throughout the body. And what we now know, there's a
• 25:21
  Speaker 2: term called social jet lag.
• 25:23
  Speaker 1: Okay.
• 25:24
  Speaker 2: And you can feel as bad as you do with
• 25:26
  Speaker 2: jet lag just by staying at home, having a normal
• 25:29
  Speaker 2: light cycle, but let's say late night eating. Because what
• 25:33
  Speaker 2: late night eating is going to do, it's going to
• 25:34
  Speaker 2: tell clocks in your peripheral tissues that it's really maybe midday.
• 25:38
  Speaker 1: Uh-huh.
• 25:40
  Speaker 2: But your brain's like, no, it's nighttime. And so there
• 25:44
  Speaker 2: is a misalignment of clocks throughout the body. And you just,
• 25:48
  Speaker 2: I mean, again, it's not lethal, but you don't feel great.
• 25:54
  Speaker 1: We'll be back in a minute with The Lightning Round.
• 25:56
  Speaker 1: The Lightning Round I want to do just a lightning round.
• 26:10
  Speaker 1: What is one thing a lot of people get wrong
• 26:14
  Speaker 1: about fitness and aging?
• 26:16
  Speaker 2: That there's, you know, if you get to a certain
• 26:18
  Speaker 2: age and you've never worked out, it's not going to
• 26:20
  Speaker 2: do you any good. There's lots of data. This is,
• 26:23
  Speaker 2: you know, yes, you can. And yes, it does. Will
• 26:27
  Speaker 2: it do everything it would have done when you were
• 26:29
  Speaker 2: 20 or 30? Maybe not, but it still has health
• 26:32
  Speaker 2: benefits for sure.
• 26:33
  Speaker 1: Well, and going from nothing to a little bit is
• 26:36
  Speaker 1: a huge gain, right? Like people who don't move at all,
• 26:39
  Speaker 1: if they walk for 10 minutes a day, like literally
• 26:43
  Speaker 1: you see these very large benefits.
• 26:46
  Speaker 2: Exactly.
• 26:47
  Speaker 1: Tell me about caffeine. We didn't talk about caffeine.
• 26:50
  Speaker 2: Yeah, so caffeine basically stimulates the autonomic nervous system, epinephrine, norepinephrine.
• 26:58
  Speaker 2: Some of the clock genes can be sensitive to this,
• 27:00
  Speaker 2: but I think there's no really strong evidence that the
• 27:05
  Speaker 2: coffee is going to modify the clock.
• 27:08
  Speaker 1: Has your research changed how you exercise?
• 27:11
  Speaker 2: It's changed how I live my life.
• 27:14
  Speaker 1: Say more.
• 27:15
  Speaker 2: Yeah. Well, I am older, too. But I've always been
• 27:19
  Speaker 2: an early morning person. So that hasn't changed so much.
• 27:23
  Speaker 2: But thinking about, you know, when do I start eating?
• 27:26
  Speaker 2: When do I stop eating? Sort of the time-restricted aspect
• 27:31
  Speaker 2: with that being a cue. Light exposure at night.
• 27:34
  Speaker 1: When do you stop eating, if I might ask?
• 27:36
  Speaker 2: I target for like 7 o'clock. Yeah. But, you know,
• 27:40
  Speaker 2: 7 to 8.
• 27:41
  Speaker 1: One tip for dealing with jet lag.
• 27:43
  Speaker 2: Get out and walk around. Or if you want to swim, swim.
• 27:46
  Speaker 2: Do something. And wherever you are, just get into sync
• 27:49
  Speaker 2: with that day as quickly as possible. But movement and
• 27:53
  Speaker 2: time you're eating to be in cycle, just, you know,
• 27:56
  Speaker 2: don't go to bed right away just because you've been
• 27:58
  Speaker 2: up all night.
• 27:59
  Speaker 1: Should we make daylight saving time permanent? Stop changing the clocks. No. Oh, God, no. Oh, interesting.
• 28:06
  Speaker 1: I thought you were going to go the other way.
• 28:08
  Speaker 2: Standard time should be permanent. Oh, okay.
• 28:09
  Speaker 1: Okay. So we should stop changing the clocks, but it
• 28:13
  Speaker 1: should be standard time, not daylight saving time. Correct. Daylight
• 28:15
  Speaker 1: saving is when you spring forward, right? Correct. So you
• 28:18
  Speaker 1: set the clocks forward, so it means six becomes seven.
• 28:22
  Speaker 1: So it gets light later in the morning. It stays
• 28:24
  Speaker 1: dark until a later time in the morning, and then
• 28:26
  Speaker 1: it stays light later in the evening. Late at night, right.
• 28:28
  Speaker 1: That's bad, you're saying.
• 28:30
  Speaker 2: Correct, for a couple of different reasons. One of them
• 28:33
  Speaker 2: is when you think, and the one that's argued most
• 28:36
  Speaker 2: is child safety, going to school in the morning, especially
• 28:39
  Speaker 2: as So if you kept that the same all the.
• 28:41
  Speaker 1: Time, kids would go to school in the dark and that's.
• 28:43
  Speaker 2: Completely in the dark. Right. And then there are there
• 28:46
  Speaker 2: are sets of data out there that, you know, so
• 28:49
  Speaker 2: standards time is based kind of in intrinsic time of
• 28:54
  Speaker 2: day sunlight cycles. Right. And and there's some data that
• 28:58
  Speaker 2: that in terms of the biology with people living on
• 29:01
  Speaker 2: more standard time versus on daylight savings time.
• 29:06
  Speaker 1: Is it right the bill that's in Congress now is
• 29:08
  Speaker 1: for permanent daylight saving time as opposed to permanent standard time?
• 29:11
  Speaker 2: Correct.
• 29:12
  Speaker 1: Why?
• 29:13
  Speaker 2: Well, it's because, well, I mean, where am I, Florida?
• 29:22
  Speaker 2: So the Society for Research on Biological Rhythms is the
• 29:25
  Speaker 2: main scientific organization, has had policy statements out for several
• 29:29
  Speaker 2: years on this. We've talked to our senators, we've talked
• 29:32
  Speaker 2: to our congresspeople, but it likely is Golf courses, places
• 29:37
  Speaker 2: where people, I don't know whether it's the theme parks
• 29:40
  Speaker 2: too in Florida.
• 29:41
  Speaker 1: Places where people go, say, after work if it's still light. Correct.
• 29:46
  Speaker 2: So it's an economic issue, right? Instead of a health
• 29:50
  Speaker 2: and safety issue.
• 29:52
  Speaker 1: Thank you for your time. It was delightful to talk
• 29:54
  Speaker 1: with you.
• 29:55
  Speaker 2: Oh, sure. That was so much fun.
• 30:03
  Speaker 1: Karen Esser is the chair of the Department of Physiology
• 30:07
  Speaker 1: and Aging at the University of Florida. Today's show was
• 30:10
  Speaker 1: produced by Gabriel Hunter Chang, engineered by Sarah Bruguier, and
• 30:14
  Speaker 1: our showrunner and editor is Jake Harper. I'm Jacob Goldstein.