Sleep pressure, behavior, and what “rest” is doing biologically

58:19>> Yeah. But so these jellyfish just like us, we like taking naps. These jellyfish like taking naps. The sea anemone on the other hand, they were actually more active during dusk and dawn and then they slept mainly during morning and that could have something to do with the fact that like their feeding has to do with tides, right? Because the water is moving in and out. So perhaps you want to be more active during the dusk and dawn and then you can be less active when the sun is high in the sky and when the sun is low in the sky, >> which kind of maps onto like nocturnal versus non- nocturnal. >> Yeah. And speaking of nocturnal versus non- nocturnal, they also had the melatonin >> that was affecting them. So melatonin, you know, that's the very famous compound that we can take in order to

59:00induce sleep. Yes. They tested it with 100 microar melatonin and the melatonin promoted both in promoted sleep in both the dal jellyfish and these anemone. So, you're saying that someone's gonna make billions of dollars selling melatonin 10 milligram 100 mill whatever packages to to see like Nemo? Yeah. >> Nemo, tell your dad we're we're coming with the melatonin. >> Yeah. Exactly. [laughter] Yeah. There's a huge market there, dude. >> Yeah. So, the now we've established that they sleep and the sleep is like pretty close to how we do it. >> We saw it both in a natural context and by trying to induce it. >> Yes. Exactly. So now the big question is

59:41why are these guys sleeping so much? >> Mhm. >> Okay. If >> if they have no brains, >> if they've got no brains, >> the way we the way we conceptualize >> Yeah. the way we conceptualize brains, they don't have these like synaptic connections that they need to regulate up and down. So why are they sleeping so much? And this is the key significant contribution of this paper. Okay, they're tying the sleep not to neural activity but to cellular activity and the idea that at the molecular level all cells need to recover. >> Oh, >> okay. Because at the molecular level, what's happening with activity is activity means high entropy, right? There's high metabolic flux. The

1:00:22mitochondria are going crazy. They're creating ATP. Now, that's going to create a lot of reactive oxygen oxygen species. Okay? And these reactive oxygen species are going to cause damage to the DNA backbone. If you remember from our DNA episode, the DNA has this phosphate backbone, right? The reactive oxygen species that come as a byproduct of mitochondrial metabolism is going to start attacking this DNA backbone. And if you ever get something like >> a doublestranded break, that's really bad. >> Okay. [clears throat] And what they could actually quantify is during wakefulness the double stranded break was happening more often. Uh so literally the the the the process of

1:01:05living of being awake and active is not only impacting your body in the physical sense that we think about it today. But the reason that our body needs sleep and rest is because at the gen at the DNA >> at the DNA level it's causing damage. >> It's causing damage and and that's that's because again I always thought like from my layman's perspective like oh we sleep cuz your brain is tired. >> Yes. >> Like that was the that was the idea. It's like you need to give your brain a rest. You're going to go crazy. >> Yeah. But really what this is identifying is that the the destructive property that happens from lack of sleep is a degradation of your of underlying

1:01:47DNA. >> Yeah. Yeah. And for higher order organisms it could be that the brain is also tired and the synaptic homeostasis model works right and that could be a thing. >> Yes. >> And it most definitely is. There's a lot of papers that do that. But this is showing that even at 600 million years back we needed sleep because fundamentally the act of living as you said degrades the molecular structure of our genetics. >> Mhm. >> Right. And what they could do is show they could actually tag um phosphorolated histone and this phosphorilation happens at doublestranded breaks and they could track that actually the longer you're awake the more double stranded breaks you're having. Okay. And if you kept these organisms awake, the breaks would

1:02:29actually build up. The craziest thing to me was they could actually they could actually use that damage to drive sleep. So, you know that homeostatic regulation that I was telling you about, like, okay, if I if I deprive these animals of sleep, then they want to sleep longer. Well, I could actually artificially >> make double stranded breaks happen, you know, expose them to UV radiation. Now, I have a bunch of DNA damage. the animals would sleep more because of more UV radiation because there was more doublestranded breaks. So, it's a direct causation now. It's not just a correlation. You've established a direct causation between DNA damage and more

1:03:09sleep. >> That's fascinating. >> Very cool. >> They they they artificially triggered >> DSBs, double stranded breaks. >> Yeah. >> After having already monitored natural behavior. >> Yep. And it triggered an increase in the amount of sleep in both the jellyfish and the ceneemy when they were exposed to uh an external factor that one of the primary things it did was create a larger volume of double stranded breaks or degradation of the molecular DNA stuff. >> And they didn't comment on this, but I've always felt that like if I'm out in the sun for really long, >> I need to I need a nap. >> I need a nap. I don't know if they're I'm not saying that the authors I'm just

1:03:51saying it's like kind of >> I don't know. >> Look, it is Southern California, so we do know what it's like to be out in the sun a lot. >> I feel like when I get sunburned and I do get sunburned, okay? Like even though like I'm brown, I do get sunburned. And then when I do, it's like I do like I end up napping for like two hours and it's the best nap. >> It's the best. It's usually the best nap. It's It's usually the best. You know, maybe that's like, you know, the DNA repair being like, finally, we get to like fix all this nonsense that he's been up to. >> This this this is good. And again, this is like again a story at the intersection of spaces I didn't expect to to sort of see, right? You you have it was like I as a DNA damage, okay, it's a neuroscience story. Oh, because

1:04:32we thought that sleep was about the brain only. Again, we we've caveed this is not saying that uh sleep is not involved in neurological activity. It is just that we can see that it is not the only >> thing that it's involved in. >> Yeah. And it's like an invariant across animals that have neurons. And one of the cool things is when you think about like why would neurons specifically need sleep? >> Yeah. >> Right. Neurons are organisms that don't divide. Right. Neurons not organisms. Neurons are cells that are post mitoic. They