The role of fasting-induced ketosis in stem cell activation and cell renewal | Valter Longo
[Rhonda]: At least, with the hematopoietic
stem cells, like I’m not sure about with that,
you know, others stem cells and other tissues.
But I know that when they’re quiescent, when
they’re not dividing, they are glycolytic,
meaning they use glucose for energy because
they don’t want to damage themselves with
reactive oxygen species being generated as
a byproduct of mitochondrial function, right?
But I do know that when they come out of quiescence,
and they come out to either self-renew or
differentiate into progenitor cells, oxidative
phosphorylation becomes their source of making
And so, I’m wondering what’s the signal…
I know you’ve published some studies on looking
at different signaling pathways that are required
to cause this hematopoietic stem cells self-renewal
mechanisms, but I’m wondering if possibly
just not having the glucose available, and
having just the fatty acids, the source of
energy that can only be used by mitochondria,
if that’s somehow also is playing a role in
making them self-renew more, or differentiate
[Valter]: I think so, and this is the work
by David Sabatini, and others at MIT, and
they’re doing work on the fat, and the role
of fat and fatty acids, etc., and self-renewal
and the activation of stem cells, particularly
in the gut.
So, yeah, there seems to be a role for fat
in that, and I think we’re still beginning
to understand it.
I think, obviously, with fasting, you produce
fat, and you produce fatty acids, and glycerol,
and ketone bodies.
So, the environment is there, and, you know,
we need to maybe understand more, how each
component that is changing is affecting the
program, so yeah.
So, we made the decision to try to, I think,
things are going very slow, and we’ve always
been very interested in people that have a
problem now, right, instead of, you know…
[Valter]: A lot of people are always like,
wow, in 20 years we’ll have this.
And we always said, you know, “There’s people
who have cancer now, they have multiple sclerosis
now, so what do you do for them,” right?
And so, our decision has been always understand
enough the mechanisms to be able to not, or
minimize the chance of making mistakes, get
to the clinical trial, and then, go back and
fill it in, right?
[Rhonda]: Mm-hmm, yeah.
[Valter]: Rather than step, by step, by step,
by step, you know, and then it’ll take you
15 years to get to clinical trial.
[Valter]: So, I mean, I’m not criticizing
the other method, but I’m just saying that
for us it has been get the mechanism, get
enough mechanism, move to the clinical trial,
and then make sure it’s safe, and…
[Rhonda]: It’s been fantastic.
I mean, you’ve been able to translate so many
different studies, I mean, it’s really quite
I’m just, sort of, thinking, in fact I just
thought about it when you’re mentioning the
ketone bodies too.
Well, ketone bodies are more, if you think
about the stem cells, and if they need energy
to differentiate or self-renew, ketone bodies
would actually provide a very energetically
favorable source because it takes less oxygen,
actually, to convert beta-hydroxybutyrate
into Acetyl-CoA, as opposed to glucose into
So, if you think about it, it’s more energetically
favorable to have ketone bodies, and so, maybe
it also helps just because it takes less energy
to do this process.
I mean, you know, it’s possible, but…
I think, there’s also mechanisms.
Again, the fasting imposes this new metabolic
profile, and the new metabolic profile requires
the stem cells for this regeneration that
So, if you got to get rid of the health of
your liver, let’s say that you fast for a
Then you must, you will produce tons of fatty
acids and tons of ketone bodies, and that
environment is gonna require the stem cell
to be renewing, and being standing by for
the day where you need to make a new liver,
essentially, or health for the liver, right?
So, this is why, I think, it’s all a part
of a coordinated response, where, you know,
you have the fat…
And by then, the fat is one of the few abundant
sources of energy also for the stem cells,
so they really have no choice but to be ready
to respond to fat metabolites so that they
Because there’s not much sugar around, and
the brain needs the sugar, by the way, right?
So, the brain needs a lot of the sugar that
is available, a lot of is made by gluconeogenesis,
so it makes sense…
[Rhonda]: Red blood cells are needed since
they have no mitochondria.
And so it makes sense that you would have
a system like that, that is fat in fatty acid
and ketone body…
[Rhonda]: Yeah, yeah, absolutely.