[Rhonda]: There’s been a really big interest
in fasting and also in limiting food intake, and limiting food intake is actually one of
the probably most, I would say, reproducible interventions that’s been shown to modulate
the aging process across multiple organisms. So, I was wondering if you could maybe describe…define
and sort of describe some of the common denominators between various modalities of limiting food
intake like caloric restriction, intermittent fasting, prolonged fasting. [Valter]: Right. Yes. So, I think that we’re at the point where
we have to start…we have to stop using terms like intermittent fasting, because it covers
almost everything, right? I mean, at least in the journalist mind, when
they talk about intermittent fasting, it covers from two hours food…not eating, to one month. And of course they’re completely different
practices and they have completely different effects. And so I think it’s important to start qualifying
what it is that we’re talking about. So, intermittent fasting, I guess it could
be a way to include let’s say alternate day fasting, and include what’s called the five-two,
so having two days a week of a very restricted diet, and maybe it could also include the
one day a week of fasting, of complete fasting. I think it would be fair to include those
three in intermittent fasting, even though they can have very different effects. Now, of course time-restricted feeding is
time-restricted feeding, which refers to let’s say how long of a time you eat per day. So 8 a.m., 8 p.m., that would be 12 hours
of feeding and 12 hours of fasting. And then calorie restriction is that…of
course you can say some people use calorie restriction to define everything that is calorie
restricted, but the people in the field talk about calorie restriction, when they hear
calorie restriction, they think of chronic reduction of calories below the normal level. So, below the level that will allow you to
maintain a normal weight, and so chronically, so if you do this all the time. And then periodic prolonged fasting instead
is what we mostly work on, and it’s very different, and it’s not intermittent in the sense that
it’s not something that has to happen in any type of cycles, frequent cycles. It can be done once a year, it can be done
10 times a year, it can be done 20 times a year, and it refers to let’s say at least
2 days of fasting or longer, or 2 days of a fasting-mimicking diet or longer. So, what do they have in common? I mean, some things may be in common, but
they are very different interventions, and they each do something different. I mean, I think we know now from the calorie
restriction field that the diet…I mean, the restriction of calories like that can
have incredible effects on diseases, diabetes particularly, but also cancer, cardiovascular
diseases. So this is really unbelievable effects. I mean, the monkeys, we know that it can wipe
out diabetes completely. It can reduce cardiovascular disease and cancer
by 50%. But the monkeys either live a little bit longer,
or don’t live longer at all. And this is what we and others, a few at least
suspected for a long time. I was a student of Roy Walford back in the
early ’90s, and it was…I mean, being around calorie-restricted people, it was very clear
to me that this was going to have problems, but it was also very clear that this was going
to have huge effects on health. [Rhonda]: For the monkey studies that you’re
referring to, there were two published, correct? One from the University of Madison and one
from the NIH? [Valter]: Right. [Rhonda]: And neither of them increased lifespan,
but they increased healthspan? [Valter]: No, no, no. The Wisconsin increased lifespan. Richard Weindruch was also a student of Roy
Walford. So, yeah, that increased lifespan. But if you look at the lifespan that is based
on the disease-dependent lifespan, so the mortality caused by major age-related diseases,
that was…there was a huge effect. If you look at the overall survival due to
where all causes of mortality were taken into consideration, then the survival curves are
very close to each other. [Rhonda]: Would that be considered maximum
lifespan? This one [inaudible 00:05:39]
[Valter]: No, this will be mean lifespan, mean and maximum, right? [Rhonda]: Okay. [Valter]: So, small effect. They don’t have maximum because I think they
will have taken…at some point they had to stop it so they couldn’t really get to full
lengths. It already took 25 years to do that. So, I think it would have been difficult to
get maximum lifespan. But the mean lifespan was extended in Wisconsin,
it was not extended at the NIA. Of course the Wisconsin study had a controlled
diet that was much worse than the NIA-controlled diet. So the NIA had somewhat of an ideal diet,
at least ideal monkey diet, and the Wisconsin didn’t. The Wisconsin was a reasonably good model
for the western diet. [Rhonda]: That’s interesting. Okay, so there’s no really…I think there
was also maybe some different genetic backgrounds as well from the monkeys but who knows? [Valter]: Yes, probably genetic… [Rhonda]: Do you know if in these studies
did they see common pathways…and I want to talk about this with you. Genetic pathways that are known to be modulated
by caloric restriction, were those changed? For example, did IGF…were IGF-1 lowered
or mTOR? [Valter]: Yeah, now I haven’t looked at those
papers in a while, but almost for sure, I mean, those were affected. I mean, calories are cut by 30%, so that would
mean 30% less proteins and 30% less sugars. So, yes, I will assume that both of them showed
effects on the nutrient-signaling pathways and including TOR and IGF-1. [Rhonda]: And I guess so that’s probably something
that’s also a common denominator between these other modalities of limiting food such as
the periodic prolonged fasting. I guess one of the major differences would
be the shift in metabolism to, when you’re fasting, to beta-oxidation, to…because that’s…is
that something that occurs during caloric restriction? [Valter]: That probably occurs. There’s probably a minimal switch to a ketogenic
mode, depending on who it is and what the restriction is. So, it is possible that chronically, when
you’re chronically restricted, it also depends how you restrict it. So for example there are human studies where
they show that because the people that are restricted were eating high protein, a high
vegetable protein diet, and the IGF-1 was not affected. So, it is possible that some of these individuals
have a diet that would block entry into even a small ketogenic mode. But overall they’re probably not, they’re
relatively in a standard metabolic mode as far as ketone bodies and fatty acids are concerned.