Podcast #129: Circadian Rhythms with Karyn Esser

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https://podcasts.apple.com/us/podcast/jacked-athlete-podcast/id1462537296?i=1000697660390

“A clock is basically a molecular timer. It’s found in every single cell in your body and it is conserved across our planet. So I don’t care whether you’re a plant or you’re a bacterium or whether you’re a fly or whether you’re a human. You have a 24 hour timer in all of your cells.”

“It’s evolved in our cells in concert with the fact that our planet rotates and we have periods of darkness and lightness, which for us corresponds to rest/activity cycles, feeding/fasting cycles.”

“If I’m a muscle cell, I wanna make sure all my metabolic pathways are primed and ready to go before I wake up. Not after I wake up. This is an anticipatory clock, so it’s gonna prep the system.”

“So before you get out of bed, the metabolic components of your muscle fiber are ready to go. And then on the other end of the spectrum, at the end of the day, it’s time to restock the shelves.”

“So you’ve been using glycogen, you’ve been using different fuels, you’ve probably got some little areas where proteins are modified or damaged or maybe your membrane or that kind of thing. And what’s the best time of day to do that? While you rest.”

“The reality is there’s more than light that actually sets the clock and what time we eat and what time we’re active are two other sort of what I would call environment or behavioral factors that will talk to the clocks largely in the peripheral tissues, so liver, muscle, fat, heart, for example.”

Misalignment: “The timing of the clocks and the periphery are not in sync with the clocks in the brain. And so with that misalignment, you’ll get some outcomes. mean, A, you won’t feel good and your performance from as an athlete is going to be diminished. But B, you’ll start seeing things like increased circulating glucose changes and mean arterial blood pressure. You know, not that it’s going to kill you, but you’re not going to feel great, right? And you’re not going to perform well.”

“How clocks can go wrong: infection. So if you’re sick, if you have inflammation, that inflammation can actually function to dampen the clock. So a lot of chronic diseases, type 2 diabetes, a variety of diseases have an association with increased inflammation. And what those will do is they’ll just kind of like sit on the clock. I mean, it still works, but it’s just not working as well.”

“There’s the timer part, which is fairly robust, and that just sort of keeps running. It’s sort of like the Energizer Bunny, it just keeps on going. But the clock has another job, and that job is to regulate a program of gene expression, which has a temporal component, but there are sets of genes that need to be regulated at certain times. So in disease, when the clock goes wrong, when inflammation dampens it, the timer works just fine and that keeps ticking. But what happens is its ability to regulate this time of day specific pattern of gene expression gets rewired in ways that are problematic.”

“This is what happens with age, unfortunately. So the timer itself keeps going, but the ability of the timer to do the jobs in a healthy way can be modified.”

“When I think about the clock, I’ve started to call it the soul of the cell. mean, it’s the caretaker, right? And if its ability to do its job is modified, that’s when we start seeing our ability to clean up, our ability to build, our ability to handle stress, respond to stress. And I’m talking like I’m a cell. So my cell’s ability to do this is just, it’s not as resilient.”

“If I eat and I exercise way off cycle, a number of the clocks in the peripheral tissues will follow my behavior rather than the light cycle from the SCN.”

“For us to be healthy, we want all our clocks to be in sync… but I would say that the SCN doesn’t directly control the phase of the peripheral clocks.”

“The data in mice are absolutely translatable to the human condition with the understanding that you compare things in the active period or the rest period, not in light and dark. So the kind of things that are going on in the dark phase of a mouse skeletal muscle are virtually the same as what are going on in the human skeletal muscle during the light phase. There’s just a swap over.”

“We don’t need light for our clocks to run… So all the light is doing is it’s doing adjustments, maybe we need to move it a little forward, a little backward.”

“The clock’s going to run inside your cells. It doesn’t matter whether you get light or not.”

“So we had a mouse model in which we had basically stopped the clock only in muscle fibers. And then we let the animals live as long as they could… And so when we went in to take a look, the tendon was calcified, no doubt about it. And it was, it was pretty severe. Why did that happen? Again, we targeted muscle. We didn’t target the tendon. But what it highlights is the amount that these different tissues are talking to each other. And so there was something that went on in the muscle that actually triggered this response in the tendon.”


“Our best guess is that the muscle released factors that had an impact on the cells in the tendon and sort of, and then those factors then inform cells in the tendon. In this case, the response is calcify… An alternative or a sort of complimentary idea is that the muscle got really weak. And so with the muscle that weak, you know, you need us, and maybe it was like, okay, we’ve got to fortify the structure here so that the animal can use this leg. And so, you know, there could be some of that kind of communication as well.”

“Energy storage in the tendon is really important. So when we look at walking and running, turkeys have given us data in this space that the amount of work the muscle does and the length excursion is actually quite small… I mean, you can think of kangaroos too. Their tendons are huge. And so, yeah, I I could imagine that when you look at the musculature of these things and you think about, OK, for survival, what’s important? I know, keeping the structure fixed, then we can get rid of mobility. We don’t need all that mobility. Let’s just fix it and fly off.”

Ageing: “It’s that maybe you don’t clean as much. And maybe you don’t build as much… But also, what you start seeing is the time alignment of these things. So let’s say classically, you sort of have active phase. And you have the different jobs in active phase and rest phase. Now some of these things start showing up at different times. So you don’t have that fine temporal resolution that you had when you were younger.”

“Immobilization is not going to stop the clock… That timer keeps running. But where the problem comes in going is going from the timer and getting the right sets of genes at the right time regulated.”

Karyn’s profile: https://physiology.med.ufl.edu/profile/esser-karyn/

Karyn’s Linkedin: https://www.linkedin.com/in/karyn-esser-a187333

154 thoughts on “Podcast #129: Circadian Rhythms with Karyn Esser”

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  149. Miguel Soler

    Thinking of a muscle cell as having an anticipatory clock that primes metabolic pathways before we even get out of bed is wild. It really highlights how inflammation doesn’t just stop the timer from going, but disrupts its ability to prep our tissues on time.

  150. Controller Tester

    Could adjusting meal time really override how the brain clock syncs each peripheral cell? It is wild that the molecular timer keeps going even when chronic inflammation disrupts its ability to regulate daily metabolic recovery.

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