One, your just rapid-fire thoughts on some of these so-called caloric restriction
or fasting mimetics like resveratrol or spermidine or hydroxy citrate,
things that have been shown to increase autophagy or polyphenols from coffee.
And maybe doing that in combination with intermittent fasting and
what your speculation would be.
But also what your intermittent fasting routine looks like, maybe
before and after your injury?
And if they're, you know, different.
And then that's it.
Well, the answer the last part is easy.
Not different.
I eat all my food within a six-hour time window and it's
no simple sugars, virtually no saturated fat, mostly plant based.
That's vegetables, some fruits, fish.
I do eat whole grains.
I'm not so convinced that, you know, whole wheat is bad for you.
I don't think I have any gluten.
Okay.
Do you do prolong fast ever or longer than a daily-time restricted?
Surprisingly, I haven't.
And then, but, you know, trying to mimic the effects of fasting.
We've worked on this a little bit with 2-deoxyglucose and with something called
DNP, which is a mitochondrial uncoupler.
2-deoxyglucose, it's glucose that doesn't have a hydroxyl group that's glucose.
That's why it's called to 2-deoxy.
But anyway, 2-deoxyglucose will be taken up in cells just like glucose is,
but it cannot be used to produce ATP.
And it competes with an enzyme called hexokinase.
That's like the first enzyme involved in the metabolism of
glucose that leads to ATP production.
So, the bottom line is if you feed an animal or a human 2-deoxyglucose,
cells in the animal will think, they will experience the effects
of glucose deprivation because there's less glucose coming in.
And, in fact, it will increase some of these protein chaperones, one called
GRP78, glucose-regulated protein 78.
It's kind of like a heat shock protein.
And we'd found that if we give 2-deoxyglucose every other day, it
can be neuroprotective in some of our models, and we published that.
Don Ingram, he wants to see if 2-deoxyglucose with increased lifespan.
So, he put it in the diet of animals.
And actually, it shortens their lifespan.
It had some adverse effects, long-term on the cardiovascular system.
So, now, that's kind of mimicking calorie restriction at kind of fundamental
global way, you know, way upstream.
The things you mentioned are, you know, can you activate pathways, like
certain pathways, autophagy, and others that are maybe kind of downstream?
And I don't know.
I think the thing is, it's kind of tricky business knowing how to know what amount
of anything that mimics fasting is enough.
For example, you may see some short-term benefit in whatever
endpoint you're looking at.
So, for example, ketones.
The 2-deoxyglucose will increase ketone levels because cells
think there's less glucose in the blood when there's actually not.
And so, ketones are produced.
But, you know, long term, it's not good.
So, you know, my advice is to stick with exercise.
I think intermittent fasting can be helpful for a lot of people.
Keeping your mind intellectually engaged, eating good diet.
There's just not sufficient data to support the use of any of these things,
you know, whether it's nicotinamide riboside, or rapamycin seems like it's
something that in animal studies looks pretty interesting, but I've been kind
of hesitant to take rapamycin myself, just given that what it's prescribed
for is suppressing the immune system.
And long-term in humans, we don't know.