[Rhonda]: Your work, you've done a lot of research on what regulates these different
clocks.
[Satchin]: Yeah.
[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.
[Satchin]: Yeah.
[Rhonda]: So, there's, there's a wide variety of processes that are regulated by these clocks.
[Satchin]: Yeah.
[Rhonda]: Maybe can you explain a little bit about the central master clock and...
[Satchin]: Yeah.
[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.