[Rhonda]: There's also the heart rate...
[Satchin]: Yeah.
[Rhonda]: Heart rhythm....
[Satchin]: Yes.
[Rhonda]: ...studies.
So you mentioned earlier the chronic diseases.
If you look at in the United States or industrialized societies in general, the number one killer,
people died in most of heart disease.
[Satchin]: Yeah.
[Rhonda]: Some sort of heart disease, you know, and obviously, lots of different things
regulate our susceptibility to heart disease.
Metabolism, obesity.
But you found some very interesting findings doing time-restricted feeding in fruit flies.
[Satchin]: Yeah.
[Rhonda]: So can you talk a little bit about that?
I'm very interested in that.
[Satchin]: Yeah.
So fruit flies are used in science for many, many years.
And they're, they have a short lifespan.
They stay alive maybe 9 to 10 weeks max.
So it helps us to figure out whether any intervention, like time-restricted feeding, will have any
positive or negative impact on health span or healthy lifespan or longevity, etc.
So what we did was, again, a very simple experiment.
We took fruit flies and we gave them food only for 12 hours during daytime, because
fruit flies are diurnal animals, they fly around during daytime, eat, and then at nighttime
they sleep, or they had access to food for 24 hours, and we measured that they were eating
the same amount of calories, and they were also moving around the same distance.
So, inside these bottles they could fly back and forth.
And at three weeks of age, their heart is very healthy.
It beats rhythmically.
And although the fly heart is not like human heart, they also have...
[Rhonda]: Most people are probably shocked.
Flies have a heart.
[Satchin]: Yeah.
So their heart is very similar genetic program.
In fact, many of the genes that are now known to be necessary for heart development in human
were discovered in flies and vice-versa.
There are many diseases in humans.
Those are now put into flies to see what do they do in the heart.
So it was a very interesting model.
Just like humans, the fly heart also becomes weaker with age.
So, by five weeks, the hearts don't beat rhythmically.
They have a little bit of arrhythmia, and then they have the same dialysis.
And so then the heart gets dilated with age.
The beat-to-beat distance also becomes very irregular.
So what we found was when these flies eat only for 12 hours, they don't develop that
arrhythmia as quickly as the normal flies do, so they are protected from this heart
disease.
Then we said, "Okay, so if we introduce time-restricted feeding later in the lifespan, then what happens?"
Because one thing we could not do in mouse study, because mice live for three to four
years, we could not introduce time-restricted feeding later in life.
But in flies, when we introduce later in life, they were also protected.
The arrhythmia reduced in flies.
And when we gave high-fat diet to flies, they also produced arrhythmia and many heart conditions
that we see in humans and those were also protected in flies.
And what is interesting in flies, we also saw the flies sleep better when they eat only
for 12 hours.
So by five weeks, flies actually are just like very old people.
They have fragmented sleep at nighttime, and they are sleepy during daytime, and that is
completely prevented by time-restricted feeding.
They have a good night sleep, they are very active during daytime, the heart pumps nicely.
[Rhonda]: Wow.
Did you measure heart rate variability?
[Satchin]: Yeah, so we did heart rate variability.
So there are seven different parameters we measured.
[Rhonda]: And that improved?
[Satchin]: Yeah, so all those seven parameters improved to some extent.
And when we introduced later in life, they also improved.
That was the surprise.
[Rhonda]: Do know what or why?
What's…
[Satchin]: Yeah, so what we found is, again, one connection was back to mitochondria.
What we found was the mitochondria were healthy, or in the sense, they did not...they may not,
maybe they were not producing as much of the reactive oxygen species.
[Rhonda]: The mitochondria in the cardiomyocyte, in the heart cells?
[Satchin]: Yeah, in the heart cells.
[Rhonda]: Okay.
[Satchin]: So we took the heart cells and did gene expression for flies.
We looked at all the genes, what we found is a big cluster of genes whose expression
actually reduced.
And those are from the electron transport chain.
So that implied that maybe they have less reactive oxygen species, or maybe reduced
activity of ETC, electron transport chain, is beneficial.
So then to prove that, we actually knocked down few components of ETC and those flies
also have better heart.
So that was one thing.
[Rhonda]: Interesting.
[Satchin]: Second thing that we found is proteostasis of protein folding is necessary and in many
other organisms people have shown that in different components of protein folding machinery.
But here, what we found is there is a new protein folding, a very newly-identified folding
machinery called ATP-dependent.
It's a chaperonin complex.
Eight different components form this barrel-like structure to fold proteins.
And this requires energy, and that CCT component has been shown to be important for various
muscle, sorry, various cytoskeletal protein folding, and it make sense for heart.
And in fact, in humans there is a point mutation in one of these ATP, sorry, CCT component
that has been shown to predispose to some heart disease.
So it's a beautiful story where found both mitochondria and this protein folding machinery
are necessary for this time-restricted feeding beneficial, if beneficial effect.
[Rhonda]: And this time-restricted feeding was 12 hours?
[Satchin]: No, it's 12 hours because flies are different from us.
They don't have thermoregulations, so when they fast for a longer time, they cannot,
they kind of can't tolerate that.
[Rhonda]: Oh yeah, they'll, they'll get cold.