1 00:00:15,396 --> 00:00:23,616 Speaker 1: Pushkin Here's a thing I did not know until very recently. 2 00:00:24,276 --> 00:00:27,586 Speaker 1: Every cell in your body has a 24-hour clock in it. 3 00:00:28,336 --> 00:00:31,636 Speaker 1: In other words, your circadian rhythm is not just in 4 00:00:31,676 --> 00:00:35,436 Speaker 1: your brain, it is everywhere in your body. And it 5 00:00:35,476 --> 00:00:37,276 Speaker 1: doesn't just affect when you go to sleep and when 6 00:00:37,296 --> 00:00:41,146 Speaker 1: you wake up. It affects metabolism. It affects repair of 7 00:00:41,226 --> 00:00:44,846 Speaker 1: damaged cells. It affects the release of hormones. Your circadian 8 00:00:44,866 --> 00:00:47,246 Speaker 1: rhythm affects all kinds of things that need to happen 9 00:00:47,286 --> 00:00:52,466 Speaker 1: in your body to keep you healthy. Unfortunately, as you 10 00:00:52,486 --> 00:00:56,976 Speaker 1: get older, the clocks in your cells stop regulating everything 11 00:00:57,476 --> 00:01:01,956 Speaker 1: quite so well. The system gets disordered. Things fall apart. 12 00:01:02,836 --> 00:01:05,396 Speaker 1: It's not all bad news, though. There are things you 13 00:01:05,436 --> 00:01:09,326 Speaker 1: can do to slow the process of degradation. And scientists 14 00:01:09,386 --> 00:01:12,406 Speaker 1: are learning more. They are figuring out how to keep 15 00:01:12,446 --> 00:01:15,566 Speaker 1: the circadian rhythm in all your cells working better into 16 00:01:15,666 --> 00:01:19,146 Speaker 1: old age so that you can stay healthier for longer. 17 00:01:21,336 --> 00:01:32,586 Speaker 1: Music I'm Jacob Goldstein, and this is What's Your Problem? 18 00:01:32,786 --> 00:01:36,106 Speaker 1: My guest today is Karen Esser. She's the chair of 19 00:01:36,146 --> 00:01:39,586 Speaker 1: the Department of Physiology and Aging at the University of Florida, 20 00:01:40,046 --> 00:01:44,046 Speaker 1: and she's a world expert on circadian rhythm in muscle cells. 21 00:01:44,766 --> 00:01:48,526 Speaker 1: Karen's problem is this. What happens to the circadian rhythm 22 00:01:48,626 --> 00:01:51,346 Speaker 1: in muscle cells as we age? And how can we 23 00:01:51,386 --> 00:01:54,186 Speaker 1: keep the system from falling apart? Part of the answer 24 00:01:54,326 --> 00:01:58,526 Speaker 1: seems to be exercise. Exercise helps keep the circadian system 25 00:01:58,586 --> 00:02:02,886 Speaker 1: functioning better for longer. Now, in her research, Karen is 26 00:02:02,906 --> 00:02:06,126 Speaker 1: trying to figure out why. What is going on exactly 27 00:02:06,326 --> 00:02:09,386 Speaker 1: at the cellular level here? And the answer to that 28 00:02:09,426 --> 00:02:13,396 Speaker 1: question could shed light on other ways to fight age-related decline. 29 00:02:14,296 --> 00:02:17,596 Speaker 1: In our conversation, Karen and I discussed why muscle cells 30 00:02:17,736 --> 00:02:22,016 Speaker 1: need a 24-hour clock, what the circadian rhythm in muscle 31 00:02:22,056 --> 00:02:26,736 Speaker 1: cells means for when we should exercise, and Also, how 32 00:02:26,796 --> 00:02:29,196 Speaker 1: your stomach and your brain can wind up in different 33 00:02:29,256 --> 00:02:32,696 Speaker 1: time zones when you travel. And how Karen's research has 34 00:02:32,756 --> 00:02:36,296 Speaker 1: led her to change her own habits. To start, Karen 35 00:02:36,316 --> 00:02:39,236 Speaker 1: told me that she didn't set out to study circadian rhythm. 36 00:02:39,716 --> 00:02:42,366 Speaker 1: She was actually looking at the effect of exercise on 37 00:02:42,446 --> 00:02:46,186 Speaker 1: muscle cells. And she wound up studying circadian rhythm because 38 00:02:46,226 --> 00:02:49,226 Speaker 1: of a finding that was so weird that at first 39 00:02:49,506 --> 00:02:50,486 Speaker 1: she thought it was a mistake. 40 00:02:51,126 --> 00:02:54,606 Speaker 2: We were looking at responses in muscle cells. in response 41 00:02:54,646 --> 00:02:56,996 Speaker 2: to an exercise bout. And the clock genes came up. 42 00:02:57,426 --> 00:03:00,806 Speaker 2: So that study, you know, 20 years ago was focused 43 00:03:00,866 --> 00:03:04,356 Speaker 2: on that with no idea of circadian clock genes. 44 00:03:04,796 --> 00:03:07,676 Speaker 1: But you found it surprising. You said, oh, after a 45 00:03:07,696 --> 00:03:11,376 Speaker 1: bout of exercise, these cells are turning on genes that 46 00:03:11,416 --> 00:03:14,076 Speaker 1: we associate with the sleep-wake cycle, with the circadian rhythm. 47 00:03:14,156 --> 00:03:15,136 Speaker 1: And that was a surprise. 48 00:03:15,256 --> 00:03:17,496 Speaker 2: Correct. But it's in the muscle. Yeah. What the heck? 49 00:03:17,516 --> 00:03:20,326 Speaker 1: So, like, why does the muscle care what time it is? And. 50 00:03:20,936 --> 00:03:24,296 Speaker 2: And really, is this just a technical problem? Did we 51 00:03:24,316 --> 00:03:27,236 Speaker 2: make a mistake? And so, you know, as a PI, 52 00:03:27,276 --> 00:03:28,826 Speaker 2: you always question your students first. 53 00:03:29,526 --> 00:03:32,426 Speaker 1: You thought somebody screwed up. You're like, there's no way. 54 00:03:32,566 --> 00:03:35,626 Speaker 2: No, no. And as usual, the students are fine and 55 00:03:35,646 --> 00:03:37,846 Speaker 2: they did the right thing. It's just the biology is 56 00:03:37,886 --> 00:03:42,146 Speaker 2: much more exciting. So that started my whole research trajectory 57 00:03:42,206 --> 00:03:44,326 Speaker 2: in that. So that's a little side note. 58 00:03:44,346 --> 00:03:47,386 Speaker 1: No, that's quite interesting. I mean, I think there's an 59 00:03:47,486 --> 00:03:50,476 Speaker 1: idea here. Let me take a stab at it. You 60 00:03:50,516 --> 00:03:52,156 Speaker 1: can tell me if it makes any sense or if 61 00:03:52,236 --> 00:03:56,586 Speaker 1: I'm reaching. I feel like there's this interesting arc over 62 00:03:56,616 --> 00:03:59,126 Speaker 1: the past, I don't know, few decades, I guess, of 63 00:04:00,166 --> 00:04:02,866 Speaker 1: realizing that more is going on in each cell than 64 00:04:02,906 --> 00:04:04,586 Speaker 1: we thought. You know, I feel like there's this old 65 00:04:04,646 --> 00:04:06,486 Speaker 1: model where the brain is sort of all the action 66 00:04:06,526 --> 00:04:08,526 Speaker 1: and then the body's just kind of dumb. The muscle just, 67 00:04:08,996 --> 00:04:11,756 Speaker 1: you know, contracts and lifts things. But as we have 68 00:04:11,776 --> 00:04:14,016 Speaker 1: looked closer, including the kind of research you're talking about, 69 00:04:14,036 --> 00:04:17,556 Speaker 1: we've seen that, oh no, the cells themselves are talking 70 00:04:17,596 --> 00:04:19,816 Speaker 1: to each other, are sort of Making what we might 71 00:04:19,856 --> 00:04:23,686 Speaker 1: call decisions or, you know, adapting. And this seems like 72 00:04:23,746 --> 00:04:26,186 Speaker 1: part of that, right? Like the fact that every cell 73 00:04:26,246 --> 00:04:30,406 Speaker 1: has its own 24 hour clock is wild and really interesting. 74 00:04:31,106 --> 00:04:33,306 Speaker 2: It is. It is. And I, you know, I'll be 75 00:04:33,346 --> 00:04:35,496 Speaker 2: real honest. When I first started, I had some colleagues 76 00:04:35,536 --> 00:04:37,396 Speaker 2: that were like, what the heck are you doing? You know? 77 00:04:37,786 --> 00:04:40,286 Speaker 2: Because I had my line of research, I had NIH funding, 78 00:04:40,306 --> 00:04:42,396 Speaker 2: and now I'm going over it. 79 00:04:42,446 --> 00:04:44,986 Speaker 1: You mean when you started looking into circadian rhythms in 80 00:04:45,026 --> 00:04:47,066 Speaker 1: muscle cells? Yeah, because they just said, oh, it's. 81 00:04:46,986 --> 00:04:51,476 Speaker 2: Just noise, or, oh, it's really, the muscle clock doesn't matter, 82 00:04:51,676 --> 00:04:54,716 Speaker 2: it's just a dumb clock downstream of the brain. 83 00:04:54,916 --> 00:04:57,816 Speaker 1: Well, why didn't you listen? Why didn't you think that? 84 00:04:58,716 --> 00:05:02,316 Speaker 2: Well, I don't know, the whole thing fascinated me. The 85 00:05:02,396 --> 00:05:05,276 Speaker 2: idea that you have this clock that's an oscillator clock, 86 00:05:05,756 --> 00:05:08,836 Speaker 2: regulating programs of gene expression in a cell. Yeah. 87 00:05:08,976 --> 00:05:11,416 Speaker 1: And in a muscle cell, in a muscle cell, right? 88 00:05:11,436 --> 00:05:11,996 Speaker 1: It's weird. 89 00:05:12,596 --> 00:05:17,016 Speaker 2: Well, yes, yes. But again, I'm very influenced by evolution. 90 00:05:17,256 --> 00:05:18,936 Speaker 2: Muscle cells are really. 91 00:05:18,806 --> 00:05:22,926 Speaker 1: Old, okay? I mean, they're evolutionarily ancient, older than, say, 92 00:05:23,206 --> 00:05:25,926 Speaker 1: eye cells or something like that. 93 00:05:25,946 --> 00:05:30,386 Speaker 2: Or even a central nervous system, right? My whole training 94 00:05:30,446 --> 00:05:33,636 Speaker 2: and kind of how I've thought about biology... has been 95 00:05:33,716 --> 00:05:36,836 Speaker 2: more that muscle is part of this system. And so 96 00:05:36,876 --> 00:05:38,836 Speaker 2: I think I was a little bit refractory to those 97 00:05:38,876 --> 00:05:41,096 Speaker 2: people that were concerned about me. Yeah. 98 00:05:41,356 --> 00:05:44,426 Speaker 1: I mean, the idea that muscles are sending signals to 99 00:05:44,446 --> 00:05:48,046 Speaker 1: the body, right? That muscles are part of the endocrine system. 100 00:05:48,066 --> 00:05:51,386 Speaker 1: Like they're not just there to move your arms and 101 00:05:51,426 --> 00:05:52,286 Speaker 1: legs around. Right. 102 00:05:52,546 --> 00:05:54,666 Speaker 2: Or look good when you're on the beach, right? 103 00:05:54,726 --> 00:05:55,486 Speaker 1: Most importantly. 104 00:05:57,296 --> 00:05:58,056 Speaker 2: So, right. 105 00:05:58,076 --> 00:06:02,676 Speaker 1: So there is this broader... realization that, I mean, does 106 00:06:02,916 --> 00:06:06,096 Speaker 1: every cell have a clock, have a 24-hour clock? 107 00:06:07,676 --> 00:06:10,676 Speaker 2: Virtually all cells. I think it's pretty safe to say yes. 108 00:06:11,036 --> 00:06:15,376 Speaker 1: And other organisms? Like, does everything, does bacteria have a 109 00:06:15,756 --> 00:06:16,866 Speaker 1: circadian rhythm? It does. 110 00:06:17,256 --> 00:06:22,826 Speaker 2: I mean, they do. But, you know, I think, you know, plants, bugs, insects, 111 00:06:23,846 --> 00:06:28,526 Speaker 2: you know, when you look across, you know, Almost everything 112 00:06:28,546 --> 00:06:30,306 Speaker 2: you're looking at is going to have a clock in it. 113 00:06:30,306 --> 00:06:32,206 Speaker 1: And like every cell in everything. 114 00:06:32,566 --> 00:06:32,766 Speaker 2: Yeah. 115 00:06:33,326 --> 00:06:35,546 Speaker 1: What is the clock? Like we're saying there's a clock. 116 00:06:35,866 --> 00:06:38,346 Speaker 1: It's not a clock. Like it's something where there's like 117 00:06:38,366 --> 00:06:41,626 Speaker 1: a 24-hour cycle where things change over the course of 118 00:06:41,626 --> 00:06:45,066 Speaker 1: 24 hours and they go back. But like what's going on? 119 00:06:45,586 --> 00:06:47,416 Speaker 2: It's a great question. And as someone that sort of 120 00:06:47,426 --> 00:06:50,356 Speaker 2: came into the field from physiology, it took me, you know, 121 00:06:50,376 --> 00:06:51,956 Speaker 2: it took a little while to kind of wrap my 122 00:06:51,996 --> 00:06:55,196 Speaker 2: head about how to think about this. So there is 123 00:06:55,376 --> 00:06:58,186 Speaker 2: what we call the core clock. And that is what 124 00:06:58,286 --> 00:07:02,026 Speaker 2: I call the timer. So that's that 24-hour timer. And 125 00:07:02,086 --> 00:07:05,626 Speaker 2: so there is a process of gene expression. Then the 126 00:07:05,666 --> 00:07:08,766 Speaker 2: proteins are made and the proteins come back in. And 127 00:07:08,786 --> 00:07:12,906 Speaker 2: then they do their function. And this takes approximately 24 hours. 128 00:07:13,206 --> 00:07:16,326 Speaker 1: Is the theory that mainly what it's doing is keeping time? 129 00:07:16,526 --> 00:07:18,866 Speaker 1: Is there like a set of gene kind of expression 130 00:07:18,926 --> 00:07:21,006 Speaker 1: and something happens and another gene is expressed and it 131 00:07:21,046 --> 00:07:23,306 Speaker 1: takes 24 hours and that's its function? 132 00:07:24,096 --> 00:07:25,386 Speaker 2: That's part of its function. 133 00:07:25,416 --> 00:07:28,436 Speaker 1: Yeah. Like that is rad, right? Like that is such 134 00:07:28,496 --> 00:07:31,376 Speaker 1: a wild evolutionary thing. 135 00:07:32,076 --> 00:07:34,296 Speaker 2: Oh, it is awesome. And I mean, part of it 136 00:07:34,376 --> 00:07:36,296 Speaker 2: is I just, like I said, I didn't train in this, 137 00:07:36,336 --> 00:07:37,926 Speaker 2: but when I, the more I read about it, it 138 00:07:37,936 --> 00:07:42,366 Speaker 2: was just like, holy, this is really cool. And, and, 139 00:07:42,786 --> 00:07:46,546 Speaker 2: and it's what we call self-sustaining, which means it doesn't 140 00:07:46,586 --> 00:07:49,086 Speaker 2: need a cue. You don't need light for it to work. 141 00:07:49,126 --> 00:07:52,816 Speaker 2: You don't, it is intrinsic to that genetic network inside 142 00:07:52,856 --> 00:07:55,746 Speaker 2: the nucleus of that cell. So it's frigging amazing. But 143 00:07:55,866 --> 00:07:58,956 Speaker 2: it has another job, and this is important from a physiology, 144 00:07:59,016 --> 00:08:02,416 Speaker 2: from an aging perspective, is that these core clock factors 145 00:08:02,456 --> 00:08:05,936 Speaker 2: will also sit on lots of different places. So in 146 00:08:06,016 --> 00:08:10,666 Speaker 2: muscle cells, they will sit on about 4,000 to 5,000 147 00:08:10,666 --> 00:08:13,726 Speaker 2: different places across the genome in a muscle, and they'll 148 00:08:13,786 --> 00:08:17,886 Speaker 2: help contribute to what I call a daily program of 149 00:08:17,946 --> 00:08:20,486 Speaker 2: gene expression. And so I think of it as a 150 00:08:20,526 --> 00:08:24,746 Speaker 2: temporal organizer of housekeeping. And again, for a muscle cell, 151 00:08:25,176 --> 00:08:27,726 Speaker 2: What you see before you wake up in your muscle 152 00:08:27,756 --> 00:08:32,226 Speaker 2: cells would be genes that are important for metabolism, right? 153 00:08:32,346 --> 00:08:33,506 Speaker 2: For oxidative metabolism. 154 00:08:33,526 --> 00:08:35,626 Speaker 1: So this is like early morning, an hour before I 155 00:08:35,666 --> 00:08:38,466 Speaker 1: get up at whatever, 6.30 every day. What's going on? 156 00:08:38,866 --> 00:08:40,906 Speaker 1: Let's do a day. Can we do a day in 157 00:08:40,946 --> 00:08:41,566 Speaker 1: a muscle cell? 158 00:08:41,586 --> 00:08:42,346 Speaker 2: We can do a day. 159 00:08:42,366 --> 00:08:45,526 Speaker 1: Okay. So it's 5.30 in the morning, an hour before 160 00:08:45,546 --> 00:08:47,596 Speaker 1: I'm going to get up. If it's a good night, 161 00:08:47,636 --> 00:08:51,136 Speaker 1: I sleep till 6.30. What's going on in my muscle 162 00:08:51,156 --> 00:08:52,096 Speaker 1: cell at that time? 163 00:08:52,736 --> 00:08:55,036 Speaker 2: So what the clock is doing at that time, so 164 00:08:55,196 --> 00:08:57,186 Speaker 2: obviously your muscle cell is kind of hanging out, but 165 00:08:57,226 --> 00:09:00,006 Speaker 2: the clock is regulating genes that are going to contribute 166 00:09:00,046 --> 00:09:03,786 Speaker 2: to your ability to use carbohydrates and fats as fuel. 167 00:09:04,066 --> 00:09:06,146 Speaker 1: So it's getting ready. It knows I'm going to get up. 168 00:09:06,246 --> 00:09:07,026 Speaker 1: That's what's happening? 169 00:09:07,346 --> 00:09:08,846 Speaker 2: Yeah, I think of it warming up the engine. 170 00:09:08,886 --> 00:09:09,276 Speaker 1: I love it. 171 00:09:09,366 --> 00:09:11,756 Speaker 2: The metabolic engine. So you get that warmed up because 172 00:09:11,796 --> 00:09:13,056 Speaker 2: you don't want to start from cold. 173 00:09:13,176 --> 00:09:13,536 Speaker 1: Okay. 174 00:09:14,736 --> 00:09:17,376 Speaker 2: And so now you wake up and you're ready to go. 175 00:09:18,216 --> 00:09:20,456 Speaker 2: And the things that are important so that, you know, 176 00:09:20,476 --> 00:09:23,416 Speaker 2: your mitochondria are ready, all these things that are important 177 00:09:23,496 --> 00:09:30,106 Speaker 2: for input or sensitivity to insulin or incoming glucose. They're already. 178 00:09:30,366 --> 00:09:32,406 Speaker 1: So just to be clear, they're primed so that when 179 00:09:32,466 --> 00:09:34,606 Speaker 1: I get up and I start using my muscles, whether 180 00:09:34,646 --> 00:09:37,166 Speaker 1: it's just going downstairs to make breakfast or going for 181 00:09:37,186 --> 00:09:40,596 Speaker 1: a jog, they're ready to take in sugar and make 182 00:09:40,656 --> 00:09:42,416 Speaker 1: energy and do their work as muscles. 183 00:09:42,796 --> 00:09:46,916 Speaker 2: Correct. Yes, exactly. So they're ready to do work because 184 00:09:46,936 --> 00:09:51,076 Speaker 2: that's what muscles do. But they obviously need fuel for that. 185 00:09:51,296 --> 00:09:53,276 Speaker 1: And then what happens over the course of the day? 186 00:09:53,586 --> 00:09:57,526 Speaker 1: So now we're up. Is stuff changing all through the day? 187 00:09:58,296 --> 00:10:02,336 Speaker 2: Absolutely. And so what you will see is that so 188 00:10:02,616 --> 00:10:05,086 Speaker 2: as you start moving, as you start working, depending on 189 00:10:05,146 --> 00:10:08,726 Speaker 2: how intense and that, some of your energy stores, like 190 00:10:08,746 --> 00:10:11,716 Speaker 2: some of your... like glycogen, that will start declining. 191 00:10:11,796 --> 00:10:14,856 Speaker 1: Yeah, which is basically stored sugar. Yeah, stored glucose. 192 00:10:14,876 --> 00:10:17,816 Speaker 2: Right. So that's going to be highest in muscle at 193 00:10:17,856 --> 00:10:20,606 Speaker 2: the start of the day. And then it'll start to 194 00:10:20,646 --> 00:10:23,136 Speaker 2: get used as you do things. Yeah. And then you 195 00:10:23,176 --> 00:10:25,866 Speaker 2: start moving into kind of the second half of the day. 196 00:10:26,226 --> 00:10:29,656 Speaker 2: And it's, again, depending on your daily life patterns, then 197 00:10:29,726 --> 00:10:33,206 Speaker 2: it's starting to prepare for the rest phase, which means 198 00:10:33,626 --> 00:10:35,126 Speaker 2: what are you going to do during the rest phase? Well, 199 00:10:35,146 --> 00:10:38,066 Speaker 2: you're going to start restoring glycogen. You're going to store 200 00:10:38,086 --> 00:10:42,046 Speaker 2: other energy substrates. The way I think about it is, 201 00:10:42,286 --> 00:10:44,926 Speaker 2: you know, you don't want to be repairing and replacing 202 00:10:44,966 --> 00:10:47,856 Speaker 2: while you're using and contracting. I see. So you're going 203 00:10:47,876 --> 00:10:50,556 Speaker 2: to send that to the rest phase. Recovery and maintenance 204 00:10:50,616 --> 00:10:53,336 Speaker 2: gets done while you're in the shop, i.e. sleeping. 205 00:10:53,456 --> 00:10:59,326 Speaker 1: Okay. So it's basically get ready to work, work, get 206 00:10:59,396 --> 00:11:01,106 Speaker 1: ready to recover, recover. 207 00:11:01,706 --> 00:11:02,146 Speaker 2: Correct. 208 00:11:02,246 --> 00:11:08,026 Speaker 1: That's the basic cycle. Right. And so how does my 209 00:11:08,186 --> 00:11:13,546 Speaker 1: exercise habit affect the circadian rhythm? Oh, my God. 210 00:11:14,886 --> 00:11:17,696 Speaker 2: We don't have enough time for this one. Right. I'm sorry, 211 00:11:17,996 --> 00:11:21,196 Speaker 2: because we're just learning some really exciting things right now. 212 00:11:21,256 --> 00:11:22,756 Speaker 2: So this is a great topic. 213 00:11:22,816 --> 00:11:23,716 Speaker 1: Okay. 214 00:11:23,956 --> 00:11:27,346 Speaker 2: Because I also have this role within the Motorpack Consortium, 215 00:11:27,376 --> 00:11:27,826 Speaker 2: which is. 216 00:11:28,126 --> 00:11:33,446 Speaker 1: Love Motorpack. Molecular transducers of physical activity. Did I get it? 217 00:11:33,446 --> 00:11:34,226 Speaker 1: I don't have it in front of me. 218 00:11:34,306 --> 00:11:37,766 Speaker 2: Exactly. So what is it about exercise that makes us healthy? 219 00:11:37,806 --> 00:11:39,986 Speaker 1: Let's just say what Motorpack is, because it's part of 220 00:11:40,046 --> 00:11:42,046 Speaker 1: the reason I want to be doing these interviews, right? 221 00:11:42,086 --> 00:11:46,096 Speaker 1: The big idea of like... We've known for a long 222 00:11:46,136 --> 00:11:48,196 Speaker 1: time that exercise is really good for you, but we 223 00:11:48,236 --> 00:11:52,136 Speaker 1: haven't really understood why at a kind of cellular level. 224 00:11:52,596 --> 00:11:55,276 Speaker 1: And motor pack is this big study trying to figure 225 00:11:55,316 --> 00:11:56,116 Speaker 1: that out, right? 226 00:11:56,676 --> 00:11:59,556 Speaker 2: Right. And I was part of the preclinical arm of 227 00:11:59,636 --> 00:12:02,576 Speaker 2: motor pack. So we worked with the animal stuff. And 228 00:12:02,596 --> 00:12:04,796 Speaker 2: what I love, I will say is, you know, we 229 00:12:04,836 --> 00:12:08,376 Speaker 2: studied 18 tissues in these animals. So we're looking at spleen. 230 00:12:08,396 --> 00:12:10,726 Speaker 2: We're looking at small intestine, different parts of the brain. 231 00:12:11,476 --> 00:12:14,736 Speaker 2: Not the usual suspects, the muscle, heart, you know, fat. 232 00:12:15,136 --> 00:12:18,736 Speaker 2: So anyway, so we are currently working on a series 233 00:12:18,796 --> 00:12:22,456 Speaker 2: of manuscripts to be submitted hopefully in the next six months. But, 234 00:12:22,616 --> 00:12:25,436 Speaker 2: you know, in terms of the systemic effects of exercise 235 00:12:25,476 --> 00:12:29,096 Speaker 2: and the way exercise or physical activity, if people don't 236 00:12:29,136 --> 00:12:33,466 Speaker 2: even want to just move, the way that can communicate 237 00:12:33,496 --> 00:12:36,726 Speaker 2: throughout your body to cells that you maybe didn't even realize, 238 00:12:36,906 --> 00:12:40,106 Speaker 2: you know, cells in the lung, your immune cells, like 239 00:12:40,126 --> 00:12:43,446 Speaker 2: I said, the spleen, The colon, the colon, you know, 240 00:12:43,506 --> 00:12:45,736 Speaker 2: with training, the colon is changing as much as a 241 00:12:45,746 --> 00:12:49,116 Speaker 2: muscle cell is. And so, you know, the health benefits 242 00:12:49,176 --> 00:12:50,716 Speaker 2: are absolutely systemic. 243 00:12:51,236 --> 00:12:54,996 Speaker 1: I'm glad to hear it. Tell me about what you're 244 00:12:55,016 --> 00:12:57,136 Speaker 1: learning about the circadian rhythm in particular. And I mean, 245 00:12:57,156 --> 00:13:00,456 Speaker 1: really what I'm asking, so you've talked about the kind 246 00:13:00,496 --> 00:13:03,686 Speaker 1: of basic circadian rhythm. And so I'm curious, how does 247 00:13:03,746 --> 00:13:07,186 Speaker 1: it change with age? And how does it change with exercise? 248 00:13:07,306 --> 00:13:09,786 Speaker 1: And then what is the relationship of exercise and aging 249 00:13:09,926 --> 00:13:11,286 Speaker 1: in the context of the circadian rhythm? 250 00:13:11,786 --> 00:13:16,436 Speaker 2: Okay, so let's start with aging. So what we've done, again, 251 00:13:16,476 --> 00:13:20,096 Speaker 2: this is all with preclinical work, but the limited clinical 252 00:13:20,136 --> 00:13:24,556 Speaker 2: data with aging and circadian rhythms is very consistent. And 253 00:13:24,616 --> 00:13:27,856 Speaker 2: that is the clock works as we get older. So 254 00:13:27,896 --> 00:13:29,876 Speaker 2: the timer still works. So if you think about those 255 00:13:29,916 --> 00:13:32,806 Speaker 2: two functions I talked about, which is the timer, and 256 00:13:32,846 --> 00:13:34,866 Speaker 2: then we're going to call it the output of the clock, 257 00:13:35,766 --> 00:13:39,946 Speaker 2: the output changes. And the output starts changing in middle age, unfortunately. 258 00:13:41,666 --> 00:13:44,506 Speaker 2: So even though the clock's working, the types of genes 259 00:13:44,566 --> 00:13:48,886 Speaker 2: it's regulating and when it's regulating those genes... Going back 260 00:13:48,936 --> 00:13:51,276 Speaker 2: to your conversation with one of the other guests you 261 00:13:51,316 --> 00:13:54,856 Speaker 2: had on was talking about autophagy or the ability of 262 00:13:55,216 --> 00:13:58,826 Speaker 2: the cell to break down proteins. Well, at a young 263 00:13:58,986 --> 00:14:03,186 Speaker 2: age in the muscle, genes involved in autophagy are under 264 00:14:03,286 --> 00:14:06,746 Speaker 2: circadian control, and they are peaking just as we go 265 00:14:06,786 --> 00:14:09,286 Speaker 2: into the rest phase, as we were talking about. Right. 266 00:14:09,316 --> 00:14:12,076 Speaker 1: This is part of the sort of cleaning up the cells. Correct. 267 00:14:14,046 --> 00:14:16,866 Speaker 2: By the time the animals are middle age, those genes 268 00:14:16,956 --> 00:14:20,406 Speaker 2: involved in autophagy are now peaking toward the end of 269 00:14:20,456 --> 00:14:23,716 Speaker 2: the rest phase. So now they're going to be coming 270 00:14:23,836 --> 00:14:25,396 Speaker 2: on at a time you're going to want to be 271 00:14:25,436 --> 00:14:27,836 Speaker 2: moving around. And so, you know, when I think about 272 00:14:27,856 --> 00:14:31,456 Speaker 2: the clock, it's like you've disordered the sequence. 273 00:14:31,556 --> 00:14:34,996 Speaker 1: It's not working as well. It's going to work, but. 274 00:14:34,936 --> 00:14:36,956 Speaker 2: It's not going to work as well. The efficiency is 275 00:14:36,976 --> 00:14:38,916 Speaker 2: going to be down and there are going to be 276 00:14:38,956 --> 00:14:40,136 Speaker 2: more mistakes made. Yeah. 277 00:14:40,256 --> 00:14:40,616 Speaker 1: Okay. Okay. 278 00:14:41,296 --> 00:14:43,156 Speaker 2: And so then by the time you get to really 279 00:14:43,216 --> 00:14:48,546 Speaker 2: old age, it's just, it's awful. It really is. When 280 00:14:48,586 --> 00:14:52,006 Speaker 2: you're younger and even when you're middle age, there are 281 00:14:52,086 --> 00:14:55,786 Speaker 2: categories of genes that are regulated across all 24 hours. 282 00:14:55,886 --> 00:14:58,546 Speaker 2: By the time you get to, in the mouse muscle, 283 00:14:58,586 --> 00:15:00,956 Speaker 2: by the time you get to old age, that gets lost. 284 00:15:01,096 --> 00:15:03,556 Speaker 2: You get a peak of genes peaking around sort of 285 00:15:03,676 --> 00:15:09,556 Speaker 2: rest to active phase transition. But that's it. And the overlap, 286 00:15:09,946 --> 00:15:13,176 Speaker 2: So the genes that are what we call clock-controlled in 287 00:15:13,196 --> 00:15:15,816 Speaker 2: the very old are not at all what you see 288 00:15:15,836 --> 00:15:18,256 Speaker 2: in the younger animal, and they're not at all what 289 00:15:18,276 --> 00:15:20,756 Speaker 2: you see in the middle age. So there's a loss 290 00:15:20,796 --> 00:15:22,896 Speaker 2: of identity as well as a loss of timing. 291 00:15:26,366 --> 00:15:28,886 Speaker 1: We'll be back in a minute with some good news. 292 00:15:38,396 --> 00:15:41,966 Speaker 1: Tell me about exercise and circadian rhythms. You know, in 293 00:15:42,006 --> 00:15:45,006 Speaker 1: the muscle, but throughout the body. Like, what does it do? 294 00:15:45,566 --> 00:15:46,226 Speaker 1: How does it work? 295 00:15:46,906 --> 00:15:49,866 Speaker 2: So, we're learning. So, again, I always, I don't want to. 296 00:15:49,966 --> 00:15:52,126 Speaker 1: Well, tell me what's clear. Like, let's start with what's 297 00:15:52,186 --> 00:15:54,326 Speaker 1: most clear and then move towards sort of the frontier 298 00:15:54,346 --> 00:15:55,246 Speaker 1: of what you're figuring out. 299 00:15:56,166 --> 00:15:59,786 Speaker 2: So, what we do know is that muscle contractions or 300 00:15:59,886 --> 00:16:04,266 Speaker 2: exercise of the muscle absolutely talks with the clock system 301 00:16:04,326 --> 00:16:08,686 Speaker 2: in the muscle. And so... What that means is, let's 302 00:16:08,706 --> 00:16:11,636 Speaker 2: say I've been exercising in the afternoon and my work 303 00:16:11,656 --> 00:16:14,116 Speaker 2: schedule changed, so now I'm going to have to exercise 304 00:16:14,156 --> 00:16:16,356 Speaker 2: in the morning because of my job, right? So I'm 305 00:16:16,376 --> 00:16:18,976 Speaker 2: going to start exercising in the morning. What will happen 306 00:16:19,056 --> 00:16:21,516 Speaker 2: is the clocks in the muscles, it may not feel 307 00:16:21,556 --> 00:16:24,376 Speaker 2: great at first, but the muscle clocks will sense the 308 00:16:24,416 --> 00:16:28,166 Speaker 2: timing of exercise and they're going to shift. And in general, 309 00:16:28,226 --> 00:16:29,926 Speaker 2: the way to think about it is, so if I 310 00:16:29,986 --> 00:16:33,526 Speaker 2: was exercising in the afternoon, they're going to shift closer 311 00:16:34,086 --> 00:16:38,216 Speaker 2: to align itself with when, you know, I am exercising 312 00:16:38,256 --> 00:16:41,396 Speaker 2: in the morning. So that will happen. It doesn't require 313 00:16:41,456 --> 00:16:43,556 Speaker 2: a change in the brain for that shift to happen. 314 00:16:43,676 --> 00:16:47,156 Speaker 1: And so what is what's actually happening when that happens? 315 00:16:47,186 --> 00:16:50,386 Speaker 1: It's sort of like they're storing energy. Like, what does 316 00:16:50,426 --> 00:16:51,746 Speaker 1: that mean in practice, that shift? 317 00:16:52,226 --> 00:16:54,726 Speaker 2: What we would predict is that, you know, so all 318 00:16:54,746 --> 00:16:56,866 Speaker 2: the things I talked to you about, what happens to 319 00:16:56,886 --> 00:16:59,306 Speaker 2: your muscle over time a day, All you're doing is 320 00:16:59,366 --> 00:17:02,386 Speaker 2: shifting all those jobs to an earlier time. So you're 321 00:17:02,406 --> 00:17:05,786 Speaker 2: going to prepare for your activity earlier and then the 322 00:17:05,836 --> 00:17:08,596 Speaker 2: recovery will also be shifted in time. So you're going 323 00:17:08,616 --> 00:17:11,176 Speaker 2: to just take your biology and shift it over. 324 00:17:11,196 --> 00:17:14,556 Speaker 1: I mean, obviously, I know the main thing with exercise 325 00:17:14,616 --> 00:17:17,476 Speaker 1: is just exercise. And like, I'm not really an optimizer. 326 00:17:17,516 --> 00:17:21,576 Speaker 1: I just want to exercise every day. But, like, what 327 00:17:21,636 --> 00:17:25,056 Speaker 1: is what you're saying about the circadian rhythm and your 328 00:17:25,076 --> 00:17:28,056 Speaker 1: body adjusting if you usually exercise at a certain time? Like, 329 00:17:28,116 --> 00:17:30,036 Speaker 1: what does that mean for how I should think about 330 00:17:30,776 --> 00:17:33,386 Speaker 1: when I exercise if I have some control over when 331 00:17:33,426 --> 00:17:33,946 Speaker 1: I exercise? 332 00:17:34,106 --> 00:17:37,426 Speaker 2: So, I mean, this is a great question. What I 333 00:17:37,446 --> 00:17:41,506 Speaker 2: would say is if you're thinking about performance, like, let's 334 00:17:41,526 --> 00:17:43,106 Speaker 2: say you're going to be in a race or you're 335 00:17:43,146 --> 00:17:46,286 Speaker 2: going to then you want to be exercising about the 336 00:17:46,326 --> 00:17:49,156 Speaker 2: time you're going to be performing. So your system is 337 00:17:49,846 --> 00:17:52,896 Speaker 2: I really don't believe in optimization, but it's best suited 338 00:17:53,076 --> 00:17:54,176 Speaker 2: for that time. 339 00:17:54,196 --> 00:17:55,776 Speaker 1: Yeah, if you want to run as fast as you 340 00:17:55,816 --> 00:17:58,316 Speaker 1: can in your half marathon, then you should try and 341 00:17:58,336 --> 00:18:00,236 Speaker 1: do your daily jog at the time the half marathon's 342 00:18:00,276 --> 00:18:01,456 Speaker 1: going to be. Correct, correct. 343 00:18:01,976 --> 00:18:05,266 Speaker 2: If you're, you know, exercising for health, that's more important 344 00:18:05,306 --> 00:18:08,546 Speaker 2: than exactly when you exercise. And again, I also don't 345 00:18:08,586 --> 00:18:11,206 Speaker 2: want to be too overly precise. You know, the clock 346 00:18:11,286 --> 00:18:13,826 Speaker 2: is not, oh, you've got 15 minutes. If you don't 347 00:18:13,886 --> 00:18:16,506 Speaker 2: exercise now, you're not going to capture it. No, it's 348 00:18:16,526 --> 00:18:17,086 Speaker 2: not like that. 349 00:18:17,486 --> 00:18:21,276 Speaker 1: So you've talked about aging and the circadian rhythm. And 350 00:18:21,356 --> 00:18:24,906 Speaker 1: basically the circadian rhythm, just the clocks are not as 351 00:18:24,996 --> 00:18:27,146 Speaker 1: effective at doing what they're supposed to do as you 352 00:18:27,186 --> 00:18:33,286 Speaker 1: get older. And then exercise basically can adjust the clock. 353 00:18:33,366 --> 00:18:37,106 Speaker 1: What effect does exercise have on aging in the context 354 00:18:37,206 --> 00:18:38,226 Speaker 1: of circadian rhythm? 355 00:18:39,086 --> 00:18:41,466 Speaker 2: So a junior faculty member in my lab has a 356 00:18:41,666 --> 00:18:44,126 Speaker 2: study on that right now, and it's very exciting. 357 00:18:44,146 --> 00:18:45,686 Speaker 1: So it's a secret? Can you tell me? 358 00:18:46,406 --> 00:18:48,906 Speaker 2: Well, it's, you know, it's his work and I want 359 00:18:48,926 --> 00:18:52,416 Speaker 2: to let him But it's good. It's very good. And 360 00:18:52,876 --> 00:18:57,486 Speaker 2: so being more active improves the function of the clock 361 00:18:57,516 --> 00:19:00,586 Speaker 2: and the clock output. And this was data looking at 362 00:19:00,646 --> 00:19:03,866 Speaker 2: both muscle and liver. So the impact of exercise on 363 00:19:03,906 --> 00:19:13,996 Speaker 2: the clock is system-wide. It's hippocampus, hypothalamus, cortex, spleen, small intestine, colon, muscle, heart, 364 00:19:14,116 --> 00:19:18,596 Speaker 2: the usual suspects. But every organ in the body is 365 00:19:18,656 --> 00:19:22,956 Speaker 2: responding to exercise in terms of their clock components. And 366 00:19:23,056 --> 00:19:26,756 Speaker 2: so I am beginning to, well, I've been wondering about this, 367 00:19:26,796 --> 00:19:29,946 Speaker 2: but I'm beginning to think about exercise as a clock 368 00:19:29,996 --> 00:19:34,446 Speaker 2: improver with age. People are looking for small molecules. So 369 00:19:34,466 --> 00:19:37,286 Speaker 2: there definitely are people out there looking to target the clock. 370 00:19:38,116 --> 00:19:42,876 Speaker 1: Small molecules meaning drugs. Small molecules meaning drugs. Or nutraceuticals. Yeah, 371 00:19:42,916 --> 00:19:46,276 Speaker 1: or supplements. Yeah. And so, I mean, as I understood 372 00:19:46,296 --> 00:19:50,586 Speaker 1: it before, the problem isn't that the clock itself, it 373 00:19:51,026 --> 00:19:53,706 Speaker 1: still keeps time just as well, but that it's like 374 00:19:53,786 --> 00:19:57,706 Speaker 1: when the clock is telling other, well, genes basically, right, 375 00:19:57,746 --> 00:19:59,516 Speaker 1: to turn on or off, that's the problem. part that 376 00:19:59,556 --> 00:20:01,596 Speaker 1: gets less effective with age. Right. 377 00:20:01,816 --> 00:20:02,036 Speaker 2: Correct. 378 00:20:02,076 --> 00:20:04,636 Speaker 1: And so the intervention isn't to make the 24 hour 379 00:20:04,676 --> 00:20:08,876 Speaker 1: thing work, keep time better. It's the relationship between the 380 00:20:08,916 --> 00:20:10,856 Speaker 1: clock and all the genes it's turning on and off. 381 00:20:11,356 --> 00:20:12,656 Speaker 2: Perfect. You've got it. 382 00:20:12,936 --> 00:20:16,316 Speaker 1: Does it matter what time of day I exercise? Let's stipulate. 383 00:20:16,736 --> 00:20:19,126 Speaker 1: Always it's better to exercise than to not exercise. And 384 00:20:19,166 --> 00:20:21,256 Speaker 1: the important thing is to exercise. And, like, I'm not 385 00:20:21,296 --> 00:20:25,446 Speaker 1: trying to win a race. Like, if I have some flexibility, 386 00:20:25,506 --> 00:20:26,026 Speaker 1: does it matter? 387 00:20:26,046 --> 00:20:27,726 Speaker 2: I don't think so. 388 00:20:27,906 --> 00:20:29,286 Speaker 1: Is it better if I do it at the same 389 00:20:29,346 --> 00:20:30,646 Speaker 1: time every day if I can't? 390 00:20:30,846 --> 00:20:33,026 Speaker 2: That's what I'm going to come back to. I would 391 00:20:33,066 --> 00:20:34,926 Speaker 2: say that, you know, so what we do know is 392 00:20:34,966 --> 00:20:37,026 Speaker 2: what time you exercise can make things shift. 393 00:20:37,246 --> 00:20:37,426 Speaker 1: Yeah. 394 00:20:37,766 --> 00:20:41,386 Speaker 2: So probably what's not recommended is, you know— seven in 395 00:20:41,406 --> 00:20:43,726 Speaker 2: the morning one day and seven at night the next day. 396 00:20:43,826 --> 00:20:46,726 Speaker 2: And this is a new field, to be honest with you. 397 00:20:46,946 --> 00:20:50,706 Speaker 2: And so based on what I understand with the clocks, 398 00:20:50,786 --> 00:20:53,966 Speaker 2: with the clocks and exercise and health, I think just 399 00:20:54,106 --> 00:20:57,126 Speaker 2: find a routine that works for you. When you're active, 400 00:20:57,206 --> 00:21:00,176 Speaker 2: how you're active, if you're active, is going to be 401 00:21:00,216 --> 00:21:05,476 Speaker 2: an important informing cue for the clocks across the body. 402 00:21:06,176 --> 00:21:11,296 Speaker 2: And that's going to be important for health. And especially 403 00:21:11,336 --> 00:21:14,416 Speaker 2: with age, one of the key issues with aging is 404 00:21:14,476 --> 00:21:18,116 Speaker 2: a loss of resiliency. So you're exposed, you get a disease, 405 00:21:18,196 --> 00:21:22,716 Speaker 2: the disease progresses either more quickly or more seriously, so 406 00:21:22,736 --> 00:21:25,986 Speaker 2: you end up in the hospital. And it just leads 407 00:21:26,056 --> 00:21:29,786 Speaker 2: to a bad sequence. And to me, this is something 408 00:21:29,906 --> 00:21:35,446 Speaker 2: that addressing... clock robustness throughout the system is a way 409 00:21:35,506 --> 00:21:36,006 Speaker 2: we can help. 410 00:21:36,326 --> 00:21:40,346 Speaker 1: Why? Like what's the relationship between the circadian rhythm and, 411 00:21:40,506 --> 00:21:42,726 Speaker 1: you know, getting more or less sick if you get 412 00:21:42,766 --> 00:21:43,366 Speaker 1: an infection? 413 00:21:44,226 --> 00:21:46,866 Speaker 2: So if I think of, you know, my cell and 414 00:21:47,026 --> 00:21:49,146 Speaker 2: the ability of my cell and my cell's going to 415 00:21:49,196 --> 00:21:52,916 Speaker 2: get immune challenges, it's going to get all these things. 416 00:21:53,516 --> 00:21:55,456 Speaker 2: And you just think of it as this little island 417 00:21:55,496 --> 00:21:58,626 Speaker 2: that has to resist outside warriors. And so the clock 418 00:21:58,686 --> 00:22:01,246 Speaker 2: is a key part of the ability for that cell 419 00:22:01,286 --> 00:22:04,766 Speaker 2: or that tissue or that human to maintain homeostasis. 420 00:22:04,926 --> 00:22:05,686 Speaker 1: To stay healthy. 421 00:22:06,066 --> 00:22:09,686 Speaker 2: To stay healthy. And so what that also means, and 422 00:22:10,066 --> 00:22:13,586 Speaker 2: I will speak from my own aging perspective, is when 423 00:22:13,606 --> 00:22:15,586 Speaker 2: you get older, it takes longer to recover. 424 00:22:15,686 --> 00:22:15,886 Speaker 1: Yeah. 425 00:22:16,436 --> 00:22:19,816 Speaker 2: But the better you can keep your clocks working, the 426 00:22:19,856 --> 00:22:22,846 Speaker 2: more resilient your cells are going to be, the more 427 00:22:23,166 --> 00:22:28,226 Speaker 2: able they are to recover and to be strong and 428 00:22:28,306 --> 00:22:30,686 Speaker 2: resilient against external challenges. 429 00:22:30,706 --> 00:22:32,896 Speaker 1: I mean, does this go back to the idea of 430 00:22:32,956 --> 00:22:35,436 Speaker 1: like there's a time for resting and the time for 431 00:22:35,496 --> 00:22:38,966 Speaker 1: resting is sort of rebuilding, cleaning up? doing these things 432 00:22:39,386 --> 00:22:41,346 Speaker 1: that take energy and that we don't want to do 433 00:22:41,386 --> 00:22:43,406 Speaker 1: when we're moving around because we need our energy for 434 00:22:43,446 --> 00:22:46,506 Speaker 1: moving around. And when we're young, that just happens. And 435 00:22:46,546 --> 00:22:50,046 Speaker 1: as we get older, that works worse, but exercising makes 436 00:22:50,086 --> 00:22:51,946 Speaker 1: it work better. Is that the basic model? 437 00:22:52,006 --> 00:22:57,366 Speaker 2: Yes, that's the basic model. Yep, exactly. I think identifying 438 00:22:57,546 --> 00:23:01,346 Speaker 2: the experiments and the ways to demonstrate that very clearly 439 00:23:01,416 --> 00:23:04,966 Speaker 2: and directly is sort of where I'm very interested right now. 440 00:23:05,506 --> 00:23:08,656 Speaker 1: And does the kind of exercise matter in terms of. 441 00:23:08,676 --> 00:23:09,996 Speaker 2: I don't think so. 442 00:23:10,056 --> 00:23:14,676 Speaker 1: Yeah. Like resistance training, cardio, fast, you know, fast cardio, 443 00:23:14,696 --> 00:23:16,976 Speaker 1: slow cardio, whatever, just do whatever and it's good? 444 00:23:17,796 --> 00:23:21,456 Speaker 2: I think so. I mean, for the clocks, okay? I mean, obviously, 445 00:23:21,496 --> 00:23:23,486 Speaker 2: if you want to grow muscle, that's versus. 446 00:23:23,526 --> 00:23:24,906 Speaker 1: No, no, but for the clocks, yeah. 447 00:23:24,966 --> 00:23:26,526 Speaker 2: For the clocks, I don't think it's going to matter. 448 00:23:27,596 --> 00:23:31,356 Speaker 1: Great. I love that answer. Just do something. Don't do nothing. 449 00:23:31,456 --> 00:23:32,996 Speaker 2: Something. Yes. Yes. 450 00:23:33,646 --> 00:23:35,226 Speaker 1: You know, we got to talk about jet lag at 451 00:23:35,286 --> 00:23:38,066 Speaker 1: some point. I'm talking here to an expert in circadian rhythm. 452 00:23:38,446 --> 00:23:41,686 Speaker 1: How could I not ask you about jet lag? So 453 00:23:42,246 --> 00:23:43,906 Speaker 1: what should I know about jet lag? Tell me about 454 00:23:43,946 --> 00:23:44,286 Speaker 1: jet lag. 455 00:23:44,646 --> 00:23:46,836 Speaker 2: So what is jet lag? Jet lag is when you 456 00:23:46,876 --> 00:23:50,456 Speaker 2: travel to. So let's say I go from Gainesville, Florida, 457 00:23:50,516 --> 00:23:53,816 Speaker 2: to Paris, France. It's a six hour difference. And jet lag, 458 00:23:53,876 --> 00:23:55,216 Speaker 2: you feel crummy. 459 00:23:55,336 --> 00:23:55,916 Speaker 1: Not great. Right. 460 00:23:56,196 --> 00:24:00,646 Speaker 2: Right. That's a circadian syndrome. Yeah. Because all the clocks 461 00:24:00,706 --> 00:24:03,726 Speaker 2: in your body get disrupted by that change in light 462 00:24:03,786 --> 00:24:06,976 Speaker 2: cycle and that time cycle, and you feel crummy while 463 00:24:07,036 --> 00:24:08,416 Speaker 2: things are out of alignment. 464 00:24:08,436 --> 00:24:09,616 Speaker 1: Okay? 465 00:24:09,676 --> 00:24:11,076 Speaker 2: Until they all get aligned. 466 00:24:11,176 --> 00:24:13,836 Speaker 1: Well, and so there's two kinds of alignment, right? The 467 00:24:13,876 --> 00:24:17,856 Speaker 1: sort of vernacular alignment, the one I think of is, oh, 468 00:24:17,956 --> 00:24:21,626 Speaker 1: my body thinks it's whatever. six at night, but it's 469 00:24:21,706 --> 00:24:25,726 Speaker 1: actually midnight. But there's another kind of alignment given that 470 00:24:25,766 --> 00:24:29,286 Speaker 1: we have clocks in all of our different cells. Like 471 00:24:29,406 --> 00:24:32,226 Speaker 1: when you get jet lag, do your different cells wind 472 00:24:32,286 --> 00:24:34,466 Speaker 1: up thinking it's a different time within your body? 473 00:24:35,126 --> 00:24:38,066 Speaker 2: Yes. Different cells in your body adjust to the new 474 00:24:38,136 --> 00:24:41,056 Speaker 2: time at different rates. So you're going to be in 475 00:24:41,076 --> 00:24:44,656 Speaker 2: that period of blah. Yeah. your brain's going to adjust 476 00:24:44,676 --> 00:24:47,736 Speaker 2: pretty fast with the light cue. But the rest of 477 00:24:47,756 --> 00:24:50,706 Speaker 2: the cells, like your stomach and do you feel hungry or, 478 00:24:50,766 --> 00:24:54,066 Speaker 2: you know, whatever, I mean, they take different periods of 479 00:24:54,106 --> 00:24:55,126 Speaker 2: time to adjust. 480 00:24:55,366 --> 00:24:59,306 Speaker 1: So even just like shifting when you sleep to, you know, whatever, 481 00:24:59,346 --> 00:25:00,226 Speaker 1: I'm going to go to sleep in the middle of 482 00:25:00,246 --> 00:25:01,776 Speaker 1: the night and wake up in the morning, you're still 483 00:25:01,816 --> 00:25:04,296 Speaker 1: not going to feel good because your body is going 484 00:25:04,316 --> 00:25:08,996 Speaker 1: to be internally inconsistent. Your stomach's going to think it's 485 00:25:09,076 --> 00:25:10,476 Speaker 1: one time and your brain's going to think it's another. 486 00:25:10,646 --> 00:25:13,466 Speaker 2: Yeah, exactly. So when I think about alignment, I'm talking 487 00:25:13,506 --> 00:25:18,266 Speaker 2: about the alignment of the clocks in my brain, you know, heart, 488 00:25:18,346 --> 00:25:21,066 Speaker 2: throughout the body. And what we now know, there's a 489 00:25:21,226 --> 00:25:22,976 Speaker 2: term called social jet lag. 490 00:25:23,156 --> 00:25:23,456 Speaker 1: Okay. 491 00:25:24,256 --> 00:25:26,456 Speaker 2: And you can feel as bad as you do with 492 00:25:26,496 --> 00:25:29,356 Speaker 2: jet lag just by staying at home, having a normal 493 00:25:29,396 --> 00:25:33,236 Speaker 2: light cycle, but let's say late night eating. Because what 494 00:25:33,296 --> 00:25:34,896 Speaker 2: late night eating is going to do, it's going to 495 00:25:34,956 --> 00:25:38,946 Speaker 2: tell clocks in your peripheral tissues that it's really maybe midday. 496 00:25:38,966 --> 00:25:39,486 Speaker 1: Uh-huh. 497 00:25:40,336 --> 00:25:44,396 Speaker 2: But your brain's like, no, it's nighttime. And so there 498 00:25:44,496 --> 00:25:48,226 Speaker 2: is a misalignment of clocks throughout the body. And you just, 499 00:25:48,526 --> 00:25:50,686 Speaker 2: I mean, again, it's not lethal, but you don't feel great. 500 00:25:54,726 --> 00:25:56,606 Speaker 1: We'll be back in a minute with The Lightning Round. 501 00:25:56,636 --> 00:26:10,576 Speaker 1: The Lightning Round I want to do just a lightning round. 502 00:26:10,936 --> 00:26:14,236 Speaker 1: What is one thing a lot of people get wrong 503 00:26:14,296 --> 00:26:15,486 Speaker 1: about fitness and aging? 504 00:26:16,386 --> 00:26:18,486 Speaker 2: That there's, you know, if you get to a certain 505 00:26:18,566 --> 00:26:20,766 Speaker 2: age and you've never worked out, it's not going to 506 00:26:20,806 --> 00:26:23,146 Speaker 2: do you any good. There's lots of data. This is, 507 00:26:23,626 --> 00:26:27,276 Speaker 2: you know, yes, you can. And yes, it does. Will 508 00:26:27,316 --> 00:26:29,226 Speaker 2: it do everything it would have done when you were 509 00:26:29,226 --> 00:26:32,186 Speaker 2: 20 or 30? Maybe not, but it still has health 510 00:26:32,246 --> 00:26:33,266 Speaker 2: benefits for sure. 511 00:26:33,326 --> 00:26:36,826 Speaker 1: Well, and going from nothing to a little bit is 512 00:26:36,866 --> 00:26:39,366 Speaker 1: a huge gain, right? Like people who don't move at all, 513 00:26:39,386 --> 00:26:42,496 Speaker 1: if they walk for 10 minutes a day, like literally 514 00:26:43,316 --> 00:26:45,476 Speaker 1: you see these very large benefits. 515 00:26:46,096 --> 00:26:46,596 Speaker 2: Exactly. 516 00:26:47,256 --> 00:26:49,956 Speaker 1: Tell me about caffeine. We didn't talk about caffeine. 517 00:26:50,676 --> 00:26:57,946 Speaker 2: Yeah, so caffeine basically stimulates the autonomic nervous system, epinephrine, norepinephrine. 518 00:26:58,486 --> 00:27:00,606 Speaker 2: Some of the clock genes can be sensitive to this, 519 00:27:00,726 --> 00:27:05,356 Speaker 2: but I think there's no really strong evidence that the 520 00:27:05,636 --> 00:27:07,296 Speaker 2: coffee is going to modify the clock. 521 00:27:08,196 --> 00:27:10,596 Speaker 1: Has your research changed how you exercise? 522 00:27:11,336 --> 00:27:13,296 Speaker 2: It's changed how I live my life. 523 00:27:14,316 --> 00:27:14,756 Speaker 1: Say more. 524 00:27:15,446 --> 00:27:19,176 Speaker 2: Yeah. Well, I am older, too. But I've always been 525 00:27:19,216 --> 00:27:22,896 Speaker 2: an early morning person. So that hasn't changed so much. 526 00:27:23,396 --> 00:27:26,356 Speaker 2: But thinking about, you know, when do I start eating? 527 00:27:26,396 --> 00:27:30,426 Speaker 2: When do I stop eating? Sort of the time-restricted aspect 528 00:27:31,186 --> 00:27:33,926 Speaker 2: with that being a cue. Light exposure at night. 529 00:27:34,326 --> 00:27:36,146 Speaker 1: When do you stop eating, if I might ask? 530 00:27:36,306 --> 00:27:40,546 Speaker 2: I target for like 7 o'clock. Yeah. But, you know, 531 00:27:40,546 --> 00:27:41,766 Speaker 2: 7 to 8. 532 00:27:41,766 --> 00:27:42,966 Speaker 1: One tip for dealing with jet lag. 533 00:27:43,936 --> 00:27:46,496 Speaker 2: Get out and walk around. Or if you want to swim, swim. 534 00:27:46,616 --> 00:27:49,956 Speaker 2: Do something. And wherever you are, just get into sync 535 00:27:49,996 --> 00:27:53,016 Speaker 2: with that day as quickly as possible. But movement and 536 00:27:53,076 --> 00:27:56,446 Speaker 2: time you're eating to be in cycle, just, you know, 537 00:27:56,626 --> 00:27:58,606 Speaker 2: don't go to bed right away just because you've been 538 00:27:58,666 --> 00:27:59,126 Speaker 2: up all night. 539 00:27:59,786 --> 00:28:06,026 Speaker 1: Should we make daylight saving time permanent? Stop changing the clocks. No. Oh, God, no. Oh, interesting. 540 00:28:06,186 --> 00:28:07,526 Speaker 1: I thought you were going to go the other way. 541 00:28:08,216 --> 00:28:09,956 Speaker 2: Standard time should be permanent. Oh, okay. 542 00:28:09,976 --> 00:28:12,996 Speaker 1: Okay. So we should stop changing the clocks, but it 543 00:28:13,036 --> 00:28:15,896 Speaker 1: should be standard time, not daylight saving time. Correct. Daylight 544 00:28:15,936 --> 00:28:17,996 Speaker 1: saving is when you spring forward, right? Correct. So you 545 00:28:18,016 --> 00:28:21,696 Speaker 1: set the clocks forward, so it means six becomes seven. 546 00:28:22,036 --> 00:28:24,576 Speaker 1: So it gets light later in the morning. It stays 547 00:28:24,636 --> 00:28:26,356 Speaker 1: dark until a later time in the morning, and then 548 00:28:26,396 --> 00:28:28,856 Speaker 1: it stays light later in the evening. Late at night, right. 549 00:28:28,876 --> 00:28:30,036 Speaker 1: That's bad, you're saying. 550 00:28:30,636 --> 00:28:32,916 Speaker 2: Correct, for a couple of different reasons. One of them 551 00:28:33,076 --> 00:28:35,836 Speaker 2: is when you think, and the one that's argued most 552 00:28:36,096 --> 00:28:39,056 Speaker 2: is child safety, going to school in the morning, especially 553 00:28:39,116 --> 00:28:41,076 Speaker 2: as So if you kept that the same all the. 554 00:28:41,046 --> 00:28:43,396 Speaker 1: Time, kids would go to school in the dark and that's. 555 00:28:43,256 --> 00:28:46,596 Speaker 2: Completely in the dark. Right. And then there are there 556 00:28:46,756 --> 00:28:49,336 Speaker 2: are sets of data out there that, you know, so 557 00:28:49,356 --> 00:28:53,956 Speaker 2: standards time is based kind of in intrinsic time of 558 00:28:54,016 --> 00:28:58,396 Speaker 2: day sunlight cycles. Right. And and there's some data that 559 00:28:58,496 --> 00:29:01,496 Speaker 2: that in terms of the biology with people living on 560 00:29:01,796 --> 00:29:05,096 Speaker 2: more standard time versus on daylight savings time. 561 00:29:06,116 --> 00:29:08,556 Speaker 1: Is it right the bill that's in Congress now is 562 00:29:08,636 --> 00:29:11,706 Speaker 1: for permanent daylight saving time as opposed to permanent standard time? 563 00:29:11,846 --> 00:29:12,746 Speaker 2: Correct. 564 00:29:12,766 --> 00:29:12,836 Speaker 1: Why? 565 00:29:13,546 --> 00:29:21,726 Speaker 2: Well, it's because, well, I mean, where am I, Florida? 566 00:29:22,206 --> 00:29:25,126 Speaker 2: So the Society for Research on Biological Rhythms is the 567 00:29:25,186 --> 00:29:29,136 Speaker 2: main scientific organization, has had policy statements out for several 568 00:29:29,176 --> 00:29:32,676 Speaker 2: years on this. We've talked to our senators, we've talked 569 00:29:32,696 --> 00:29:37,616 Speaker 2: to our congresspeople, but it likely is Golf courses, places 570 00:29:37,716 --> 00:29:40,316 Speaker 2: where people, I don't know whether it's the theme parks 571 00:29:40,376 --> 00:29:41,516 Speaker 2: too in Florida. 572 00:29:41,556 --> 00:29:46,366 Speaker 1: Places where people go, say, after work if it's still light. Correct. 573 00:29:46,566 --> 00:29:50,596 Speaker 2: So it's an economic issue, right? Instead of a health 574 00:29:50,696 --> 00:29:51,796 Speaker 2: and safety issue. 575 00:29:52,496 --> 00:29:54,636 Speaker 1: Thank you for your time. It was delightful to talk 576 00:29:54,676 --> 00:29:54,976 Speaker 1: with you. 577 00:29:55,296 --> 00:29:56,936 Speaker 2: Oh, sure. That was so much fun. 578 00:30:03,986 --> 00:30:07,126 Speaker 1: Karen Esser is the chair of the Department of Physiology 579 00:30:07,166 --> 00:30:10,496 Speaker 1: and Aging at the University of Florida. Today's show was 580 00:30:10,596 --> 00:30:14,536 Speaker 1: produced by Gabriel Hunter Chang, engineered by Sarah Bruguier, and 581 00:30:14,576 --> 00:30:17,936 Speaker 1: our showrunner and editor is Jake Harper. I'm Jacob Goldstein.