Rhonda: Hello, everyone. Today my guest is Dr. Satchin Panda, who is a professor at the Salk Institute for Biological Studies in La Jolla, California, where he studies the body's internal circadian clock, what regulates their circadian clock, and in turn, how this affects a wide variety of processes including our metabolism, our sleeping patterns, and how active we are, and so much more.
Satchin, considering that every single living organism on the planet Earth has this internal biological clock, their circadian clock, can you explain to people who've never heard what a circadian clock is, what it is and why it's so important?
Satchin: Yes, so all lives on this planet evolve under a rotating Earth. So that means for 12 hours, approximately 12 hours they had access to light and for another 12 hours they were in darkness. So, that environment, that changing environment put a tremendous pressure for them to come up with a timing mechanism so that they can anticipate when it's going to be evening or when it's going to be morning so that they can time their activity and sleep accordingly. So that's why almost every organism on this planet have this internal clock that help them anticipate time.
And why this is important is if you think about a diurnal organism, an animal that's active during the daytime, the animal has to anticipate when evening is going to come so that he can rush back to the cave or somewhere, some hiding place. So similarly, just before the dawn, this animal has to wake up before even light hits, and then go out and get the first grub. So that's why there is this tremendous pressure to have this biological clock or internal timing to essentially anticipate what is going to happen.
So for most people, we know when we go to bed, maybe after six to eight hours, we wake up. So our clock actually tells us, "Yes, it's going to be morning. Get up now." So similarly, almost every part of our body has clocks that help us to anticipate when the food is gonna come or when we are supposed to run, when we are supposed to take rest. So, what we are learning is almost every organ in our body has a clock and it helps this organ to be at peak performance, peak activity, at certain time of the day, and then to rest and rejuvenate at the other time of the day.
Rhonda: So, is this internal biological clock, the circadian clock, it's not something that we're just immediately born with, right? It's not something that just...
Satchin: Yes. So when we are born, we, kind of…when babies are born, they actually don't have this daily 24 hours rhythm in activity or sleep. They don't to bed for six or seven hours. So what we suspect is although they have a clock, those clocks are not wired together. And at the same time, babies also need a lot of food, because that's their growth phase. So, during the first maybe four to six months, the babies wake up in every three to four hours, cry, eat a little bit, and go back to sleep, and then wake up again, and do that.
Then after 8 to 12 weeks, they actually begin to have some kind of consolidated sleep. So they go to sleep and wake up at the right time, wake up after a few hours, but it's not tied to light-dark cycle. So they kind of drift. So that's the phase many parents may not notice because we now live in a very artificial environment, but that's the time when there is a clock but it's not tied to outside light and dark cycle. So around six months of age, that's when the whole development process and the clock is functional, it's tied to light-dark cycle, it's wired properly, so the babies go to bed, hopefully, in the evening and then sleep for nine to ten hours, wake up. So when we are born we do have clocks, but they are not connected together until about four to six months of age.
Rhonda: Oh, interesting. And you mentioned...so there's, there's clocks in all of our organs and there's different…your work, you've done a lot of research on what regulates these different clocks.
Rhonda: There's a master regulator clock, and there's other clocks in different organs. Maybe you can explain. I read somewhere that something between 10% to 15% of the entire protein-coding human genome is actually regulated by these circadian clocks, and anywhere between around, like, 40% to 50% of those genes are actually involved in metabolism.
Rhonda: So, there's, there's a wide variety of processes that are regulated by these clocks.
Rhonda: Maybe can you explain a little bit about the central master clock and...
Rhonda: ...what regulates that?
Satchin: [laughs] Yeah. So this is a field of study that is actually not driven by a disease but pure curiosity. So for a long time, people thought that there might be a master clock in the brain because we always connect circadian clock to sleep-wake cycle. And fortunately, there was actually a master clock. And in fact, almost 40, 45 years ago, people who are working on different parts of the brain…because at that time, 40 years ago, people thought that different parts of the brain regulate different behavior. So they are defined like cubic millimeter area of brain that regulates something.
So we're systemically taking out parts of the brain in mouse, rodents, and different larger rodents, and then figure out that when they hit this small part of the brain called suprachiasmatic nucleus, so that means we know that our eyes send optic nerves that crisscross and there is a part of the brain called optic chiasma, so it's above the optic chiasma. So that's why suprachiasmatic nucleus. So that's...
Rhonda: Say that 10 times fast. [laughs]
Satchin: Yes [laughs]. Suprachiasmatic nucleus or SCN, it's composed of around, say, 100,000 neurons, I guess, in humans, really small, maybe one millimeter by one millimeter. That's the size of this brain part. If you remove that brain part in a hamster, then this hamster doesn't, will not have any sense of time and go to sleep at random time and will wake up after two or three hours and it continues. But what is most exciting is if we take SCN from another hamster and transplant, it's like a brain transplant experiment, then this hamster will get all the rhythms back.
That's the earliest example of neural transplant transferring behavior from one animal to another animal. And that essentially established that there is part of the brain that accesses master circadian oscillator or circadian clock because it orchestrates this daily rhythm in waking up and going to sleep. And just imagine, only when we are awake, we eat, or we exercise. So that's why all other organs related to eating, for example, our gut, our liver, our fat, all of them are driven by this feeding behavior. Similarly, our muscle is driven by when we run. So that's how the SCN acts as the master circadian oscillator. So if we damage the SCN then we lose all circadian rhythm.
So what happens in some of the neurodegenerative disease, like very advanced stage of Alzheimer's disease dementia, if the SCN, this part of the brain is affected, then people lose their sense of time in terms of when they go to bed or when they stay awake. So this presents slowly, they turn into a state where they don't have a sense of day or night. They stay awake throughout the night and may be sleepy throughout the day. So that's why this master clock is so much important for our health.
Rhonda: And that might also have a feed-forward loop because then, you know, if your master clock is thrown off and you're awake when you're supposed to be sleeping and sleeping when you're supposed to be awake, that's also been shown to affect hippocampus and long-term potentiation. So, you know, you've got this, sort of feed-forward loop. But specifically with regards to the, the master clock, light is what regulates this master.
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