Fasting associated with sickness behavior critical to surviving bacterial infection | Guido Kroemer

[Rhonda]: That’s the question. Do we know the threshold for the stress threshold
for, you know, activating autophagy, and when that pushes the mitochondria then to permeabilize
and cause cell death? Like, where, for example, with Valter’s work
in mice, he had done 48-hour fasts and there was both autophagy and massive apoptosis occurring. So, is it just the intensity of the signal
that can then say, “Okay, autophagy is not going to work here. We got to die.” Or do we know? [Dr. Kroemer]: Well, autophagy in used in
most cell types, while apoptosis is occurring in selected cell types. So what Volter has been observing, if I remember
well, is destruction of leukocytes, right, white blood cells, which are very easily to
be rebuilt. And so, the loss of 50% or 75% of leukocytes
can be easily repaired in a few days. And it is a way to adapt the repertoire of
immune cells to changing circumstances. It is a way also to inhibit unwarranted inflammatory
reactions. So depending on the context, induction of
autophagy can be actually a subtle way to avoid excessive inflammation. One example is the so-called sickness response. So, a cat or a dog or a human being or a mouse
that is sick, that has a bacterial infection, will hide away, avoid light and noise, and
will not eat. It’s a classical phylogenetically conserved
reaction in most cases of bacterial infection. And so this phenomenon leads to changes in
the metabolism. Ketone in the production of ketone bodies,
the reduction of glucose levels, presumably also induction of autophagy, and altogether
these mechanisms avoid excessive inflammation that may be lethal. So Aslan Medzhitov published a paper in cell
last year showing that force-feeding mice or just increasing the glucose levels to a
normal concentration was sufficient to make bacterial infection that otherwise would have
been able to cope with lethal. [Rhonda]: Wow. So, I know in humans too. And we have a bacterial infection, for example,
a stomach virus or something that’s bacterial of origin, you don’t eat as well. So, it sounds like it’s sort of a protective
mechanism. [Dr. Kroemer]: It is. [Rhonda]: That’s really interesting. I didn’t know that.

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