[Rhonda]: Have you guys ever looked at, like, DNA damage or repairing any sort of challenge?
Like if you irradiate...
Like animals that are eaten, you know, on a time-restricted, you know, feeding sort
of schedule where they're eating their food, being fed their food, you know, within 10
hours or so, and then challenge them.
[Satchin]: With radiation or something?
[Rhonda]: Can they, like, repair the damage better because they're fasting longer?
[Satchin]: Yeah.
So the circadian clock itself has a huge impact on DNA damage repair and radiation damage
repair.
So a few years ago we had done a simple experiment that got highlighted in National Cancer Institute
website.
There's a very simple, straightforward experiment.
We always asked...we asked a very simple question, that is, "How come humans' skin is always
exposed to sunlight or UV radiation and many people get skin cancer but they never get
hair cancer?"
Because a hair follicle has the most rapidly dividing cells.
And so one would expect that they must be most sensitive to radiation damage.
And if there is any radiation damage, that's where the tumors will start.
And we rarely see that.
So we went back and checked and we realized that the hair follicles at the base of the
hair actually have a very strong circadian rhythm.
And every evening that circadian clock repairs all the damaged DNA and makes sure that the
hair can grow back the next day, next morning.
And then we asked, "So what is the real significance in real life?"
So we took these mice and then did a simple experiment.
That is, you know, for many bone marrow transplant experiments, mice are irradiated, and then
their bone marrow is depleted and one can put the new bone marrow in.
And they get irradiated to the same extent as humans do.
They don't die, they actually survive pretty well.
And if we irradiate mice in the morning, 8:00, then those mice lose 85% of their hair.
And if we irradiate the same mice with the same dose at 8:00 in the evening they retain
85% of their hair.
So it's a big, like really, black and white difference because these morning irradiated
mice essentially become bald very quickly.
And the evening irradiated mice, they keep their hair perfectly fine.
Now if we take circadian clock mutant mice where the circadian clock is absent, irrespective
of what time we irradiate the mice, they always lost hair.
Of course the story was much more about what...which DNA repair enzymes are regulated by clock
and how this clock works, but this is a very simple, straightforward experiment.
And similarly people have also shown many patients do go through partial hepatectomy.
Or people who have liver cancer, part of the liver is resected, and then the liver grows
back.
And, in mouse experiments at least, if partial hepatectomy is done in the evening, then those
mice recover much faster than those where the hepatectomy was done in the daytime.
So that has inspired some people to think about this surgery time, what time surgery
should be done and/or radiation should be done.
So these are some just new ideas that have just come up in animal models in the last
five to 10 years, so it will take some time to really get some traction in human studies.
[Rhonda]: Yeah.
It will be interesting to figure out whether it's, you know, the combination of is it because
they're, you know, getting more rest during that time, during the evening, and then they're
resting, fasted and resting, and so, you know, the combination of them all.
[Satchin]: Yeah.
So we know that the tumors grow slower in mice that eat only within certain times.
So time-restricted fed mice, if we just implant a tumor, then the tumor will not grow as much
as the mice that eat randomly the same number of calories.
[Rhonda]: Wow.
[Satchin]: And that also jives with another piece of data that came from Ruth Patterson's
group that women who fast for 13 hours overnight are protected from breast cancer.
[Rhonda]: They have, like, a 36% lower breast cancer occurrence.
[Satchin]: Yeah, yeah.
[Rhonda]: Yeah.
So that's really cool.
I wonder if with at least the animal experiments where you're implanting the tumor and they're
fed at a time-restricted feeding schedule, then if they're having more apoptosis, more
autophagy, more DNA repair, all these things are all sort of simultaneously happening because
they're in a fasted state for longer?
[Satchin]: Yeah.
[Rhonda]: Possibly?
[Satchin]: So it's possible.
[Rhonda]: Yeah.
[Satchin]: Yeah.
[Rhonda]: Very cool and interesting.