Sleep 8.3 Peripheral Clocks: Synchronizing the Body Beyond the Brain

Name: Sleep 8.3 Peripheral Clocks: Synchronizing the Body Beyond the Brain
Uploaded: 2025-11-25T08:42:52.270Z
Duration: 6:27
Description: The impact of peripheral clocks on tissue-specific functions and their synchronization with environmental cues like light and feeding cycles.

The impact of peripheral clocks on tissue-specific functions and their synchronization with environmental cues like light and feeding cycles.

Video Breakdown:

00:00 Introduction to Peripheral Clocks

00:34 Molecular Mechanisms of Peripheral Clocks

01:54 Study on Peripheral Clocks in Baboons

02:52 Gene Expression and Circadian Rhythms

04:31 Coordination of Circadian Physiology

05:23 Misalignment and Synchronization Challenges

05:53 Differences Between SCN and Peripheral Cells

So that's the central clock. And I wanted to go quickly through the peripheral clocks. So, nearly every cell in organ has a cell, autonomous molecular clocks. Probably the exception is red blood cell because it doesn't have a nucleus. But you could see that there are molecular clocks in obviously in the brain, in all the parts of the brain as well.
Heart, lung, gut, liver, pancreas, the adrenal system, adipose skeletal muscles, and the fibroblasts as well. And these peripheral clocks basically share the same transcription and translation feedback loop, that the SCN does. Just to highlight that, you can see that these peripheral clocks has the same CLOCK and BMAL and PER CRY feedback inhibition.
And they also have the similar secondary loops, which help stabilize or regulate the primary loops. And these, rhythms regulate certain clock outputs. So, providing rhythmic biological processes, and these transcription TTFL loops directly regulates about 10 to 40% of tissue transcriptome.
And each are unique to the organ function and time of day. So the heart, these TTLs will regulate the contractility molecules or energy substrate utilization. And then you have post translation modification to adjust to the phase, and you have different response elements to affect the inputs. So this would change the, the phase, maybe a little bit of the period of the molecules within each of the cells.
And so this is a list of the various promoters and you could see how light or lipid or cholesterol and glucocorticoids have different response elements to affect this primary cycle. So this is an interesting study that evaluates peripheral clocks. This was published by Satchidananda Panda's group in Scripps and this was published in Science in 2018. This was a study done involving 12 baboons. And, what this study required was that there were 12 baboons were kept in strict dark light cycle and a strict meal rhythm. And so you could see you have the daytime, nighttime when they're going to sleep, and you have the mealtime, which were given at very specific times of the day.

And you could see that the corresponding changes, the temperature and then the cortisol, levels as well. And for every two hours, unfortunately, each baboon was subsequently sacrificed. And then you had acquisition of all these different types of tissues where you could assess the transcriptome. And they did it so that you could see the, the changes that happen throughout the course of the day.
And you could see here that you have the multiple genes and transcriptomes here, and you can see that a lot of them are what's called universally expressed genes. And many of them are specific to the tissues. And you can see the cyclical genes or circadian genes are involved in a lot of these cells.
And if you take a look at the thousands of cycling genes that are involved in each of these organs, you can see that the brain has a good significant portion of these cyclical genes. Obviously the endocrine, digestive muscle and renal organs as well. The liver actually, interestingly, had a small amount, and this may be just because the liver is much more responsive to food as a zeitgeber compared to light.
But that is an interesting observation. But you could see here basically the expression of these genes categorized according to each of these organs or across time. You can see that there are basically two major bursts. There's one that happens at ZT8, which is corresponds to about 2:00 PM and then there's a late night dawn, approximately 4:00 AM.
Then you had a quiescent zone about midnight. You could see a dramatic difference in the peaks of these genes. So at ZT8, about 11,000 genes are expressed, or at, at its peak. And then, at ZT 22 or at 4:00 AM 5,000, and at the nadir only 696 genes.
So the circadian physiology isn't really driven by a single clock. It's a network of clocks that needs coordination. And so the suprachiasmatic nucleus, or the SCN, is the conductor synchronizing the peripheral clocks and organs throughout the body. Now, the old traditional view was that the SCN had a relationship with a peripheral, just like a master had a relationship with its slave that basically it had a very strong sort of control and command over the rest of the body. But our new view is that it acts more like a conductor that orchestrates the multiple parts of the instruments that has their own rhythm. And so the light is the most powerful synchronizers, but behavior cycles like activity, feeding, and sleep also feeds back to the shape timing.
And so when these cues are aligned, the system runs smoothly like an orchestra playing in time, but when misalignment occurs, the rhythm drifts apart. And this could lead to mismatched timing between tissues and ultimately impaired physiology. And the opportunities for misalignment are actually multiple. You could have disruption from environmental disruption, you have irregular behaviors, and you can also have desynchrony between the organs, and even within the organs and the cells. And it's important to recognize that the SCN is a different than the peripheral cells. So the SCN is strongly coupled because of the paracrine electrical signals that I showed in my previous slide.
The peripheral cells, however, are poorly coupled, because they don't have the same mechanisms, and so they require continuous synchronizations by various zeitgebers.

Course episodes

Sleep 8.1 Introduction to Circadian Physiology

Sleep 8.2 The Suprachiasmatic Nucleus: The Body’s Master Clock

Sleep 8.3 Peripheral Clocks: Synchronizing the Body Beyond the Brain

Sleep 8.4 Systemic Zeitgebers: How the SCN Coordinates the Body

Sleep 8.5 Non-Photic Zeitgebers: Meal Timing, Exercise, and Metabolism

Sleep 8.6 Understanding Process C and S in Sleep Regulation