Genetic Diseases as Models of Aging (David Sinclair Book LIFESPAN – Part 7)


This is video number 7 out of the
series on David Sinclair’s book, “Lifespan.” I’ve loved doing this series because
this is what this channel is about – improving a healthy lifespan. His goes
deeper into research although mine gets pretty deep there too sometimes. Maybe a
little too deep, and my channel gets a lot deeper into actually assessing these
metabolic parameters, these metabolic profiles for patients, helping patients
understand where they are so they can make the changes they need to make, and
helping again with medications if that’s needed. Today’s video is on genetic disease
models in aging. He spent some time talking about a lot of different people.
One of them was Nir Barzilai. And Dr. Barzilai isn’t Einstein looking
at metformin. Well, we had another video where we talked about that. Another
person that he talked about was someone he calls his friend,
Valter Longo. Now speaking of genetic models of disease, Dr. Longo spent a lot
of time working with folks that have a thing called Laron’s syndrome.
It’s a genetic pool found mostly in Ecuador. It’s a group of little people with
Laron syndrome who have short stature. As I mentioned, they’re from Ecuador. In
Ecuador, they have decreased cancer rates, decreased heart attack rates, stroke rates.
They don’t get diabetes and insulin resistance. They have more deaths due to
car wrecks and trauma because the world is not… does not fit their stature. It’s
built for bigger people. Then they have no problems with diabetes or the other
things that the rest of us tend to have problems with. When you get into their
genetics, they have a growth gene mutation (TOR-S6K). it’s the same growth
gene mutation that you tend to see in long-lived dwarfs in multiple different
very different species. There’s a yeast species with this. There are fly species
with this, and there are mice species with this. And with all of these species, you
tend to see much much higher lifespan because they don’t have the anabolic
diseases, the inflammation, the diabetes- related problems that the rest of us
tend to have. So it’s a very interesting model for disease. And as you may
remember, Valter Longo and his book focuses very
much on diabetes-related diseases. And in my channel, I focus very much on the
diabetes-related diseases and an inflammation associated with that. That’s
why he got so deep into fasting, fasting mimicking diet.
Dr. Sinclair in his book also talked about a couple of genetic disease models.
The one that he focused on was called Werner’s syndrome. It’s premature aging.
Kids in their preteen years look normal, but there they have a problem – a mutation
with slow growth suppressor 1 or SGS1. This codes for DNA helicase. Now if this
is starting to lose you, just hang in there with me just a minute because
it’ll start help it will get there. We will start understanding where this is
going. That DNA helicase untangles tangled DNA threads and repacks that
tightly. This as you see a couple of pictures of kids and again what in there.
We’ve got a 15-year-old and then she’s 48 and looks like she’s 80 or 90.
That’s typical. That’s for what you see with Werner syndrome folks. They age too
quickly. Now remember talking about packing and unpacking DNA. You remember
his analogy of a demented pianist going to a concert and the pianist is
excellent in the beginning but then they add a note and then another note. In the
first couple of times, you say, “Well, you know I heard it, but it’s not really
affecting the show.” But then it gets more and more and more, until there’s just
chaos, and it ruins the show. Basically, what he’s talking about is some things
that a gene that he he’s describing as causing early aging there. Werner
disease mutants were aging rapidly. They were madly unpacking like a
vacuum-sealed bag of yarn that had been ripped open. In other words, they had
tightly-bound histones, chromosomes, the way that we epigenetically pack our DNA.
But then again, it was like pools had been torn into it and huge loops were
coming out. Remember ERC loops? These ERC loops he found and demonstrated them in
yeast Saccharomyces cerevisiae, Baker’s yeast. So again, I hope this helps you
focus and understand some of the models, some of the things he talks
about in the book. He is noted for the discovery and use of many of the…
excuse me… the sirtuins… SIRT1 I think was one of his big discoveries, and
these sirtuins are the proteins and enzymes that are very much involved in
helping tightly-packed that DNA back so that our body can manage it. Thank you
again for your interest. This is Ford Brewer. I started off my career as an ER doc. And
that can be frustrating because most of the things bringing patients into the ER
can and should be prevented, like heart attack and stroke. So I went to Johns
Hopkins for training in prevention, did well, ended up running the program,
trained dozens of docs there, and have trained hundreds and even over a
thousand doctors since then in preventing disease. What’s even more
important is I’ve helped thousands of patients prevent heart attack and stroke
rather than waiting for the devastation and hoping for a cure.

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