[Rhonda]: But the other thing I thought about that was very interesting, and I'm not sure
if you've...you've probably read this paper, but it came out of Japan a few months ago,
I don't remember the group, but they were looking at a variety of different biomarkers
in the elderly population, in centenarians, in semi-supercentenarians, and in supercentenarians.
And they looked at all sorts of biomarkers that are related to aging, so it looked at
telomere length, they looked at senescence, immunosenescence, they looked at all sorts
of inflammatory biomarkers. They looked at metabolic markers, glucose regularly, you
know, insulin sensitivity, they looked at kidney function, you know, the whole pack,
just tons of different biomarkers. And they were trying to find which biomarkers
were consistent with healthy aging in all populations. So, not just, you know, to make
it to centenarians, but to make it to every single age group. And what was identified
was the only biomarker that was consistent with all the age groups was inflammation.
So, lower inflammation was predictive of vitality, and cognitive function, and it was considered
to be the only thing that was driving the aging process, or that could predict mortality
aside from age itself. And I was thinking about how monocytes, macrophages, and neutrophils,
these are the parts of the immune system that are the myeloid lineage, which is, you know,
we have more of them when we're older. They actually produce a lot of really nasty
chemicals, hypochlorite, hydrogen peroxide. So, the myeloid lineage is producing lots
of nasty inflammatory chemicals, so it'll be kind of interesting to look and see. I
mean, I'm totally just speculating here, but if there's some way...if you to make a...if
you could regenerate the immune system to resemble more of a youthful phenotype, first
of all, it'll be interesting look at centenarians to see if they have more balance, right, if
they have more of an immune system that has more lymphoid and myeloid, so it's not so
asymmetric. That would be interesting to see, but also, whether or not, if that plays a
role in healthy aging. [Valter]: Yeah. I think we need to be careful
with the inflammation as a cause of aging. I see it the other way around, I see it as
the aging is the cause of inflammation. And that makes sense, right, because inflammation
is really can come from dysregulation of immune cells and other cells in the body. So, yeah,
so I think it's really the evidence, the inflammation is the driving...the driver is not there.
There's very few studies actually showing that, you know, by increasing a little bit
of inflammation, increase in aging, they're not there. It's possible but this doesn't
seem likely, you know. I look at it as much more in the sense of
program, meaning that all organisms have a program, and this program is there to keep
them healthy, and young up to a certain point, and now, there are ways to make these programs
longer, or shorter, and I think the centenarian just happened to have programs that are stronger
and longer. And then, when these programs fail, the inflammation is one of the things
that you see as well, and it happens together with a lot of other problems. But certainly,
inflammation, I mean, as a marker, is a very important one. So, if you look at C-reactive
protein, for example, or Interleukin-6, in any intervention, they should do, you wanna
see them coming down, and this is a good indication. As we've done for our fasting-mimicking diet,
where we've showed that almost every patient that...I mean, we showed a decrease in inflammation
in the mice that were given the fasting-mimicking diet started at middle-aged. But we also saw
it in the human population aged 20 to 70, where everybody they had high C-reactive protein
came back down after 3 cycles the FMD, came back down to their normal levels. But again,
that's probably indicating that the systems were not working properly, and now you bringing
them back to a prior...you know, maybe you're regenerating part of the, you know, bone marrow
and maybe also you killed some bad cells in the spleen, etc., etc. And so, the result
of that is the last inflammatory markers that are being released. The liver, also, we've
shown they undergo cycles of atrophy and regeneration. So, all of these organs are contributing to
information, and so, it's important that with an intervention, you see also an effect in
an inflammation, because it tells you that the intervention is working, the system is
being reset back to a more youthful state.