Get the neatest job. I learned so much from patients and friends. For example, a
patient and friend just recently sent me an article yesterday. It's by David
Sinclair. It's the article where they restored
sight to a mouse by manipulating their epigenetics, the genes that read the
genes that read for proteins which in turn read the DNA.
Now, why is that interesting? And does that hold potential for restoring sight?
Yes, but actually even maybe bigger. Restoring things like paralysis and
spinal cord, yes. And maybe bigger than that too. But the reason I say maybe
bigger than that is what this is doing is demonstrating that we are not losing
our DNA. We knew that theoretically when we age and we become insulin resistant
for example, and we get all of the things that go along with that inflammation and
then heart disease, stroke, blindness, kidney disease. We still have those same
genes, but for some reason, we're unable to read them. And this was the article
that talked about that. But I'm getting ahead of myself. Many people may not have
heard of David Sinclair. He's a Ph.D. level doctor in aging, world-class researcher
in aging at Harvard. Wrote a book recently called "Lifespan." I've done a
video series on this book because it covers a lot of the things, a lot of the
topics that I've covered in my channel. He's gotten a lot of airtime recently
since he appeared on Joe Rogan Experience. Folks that appear on Joe
Rogan get a lot of airtime. Talks about the hallmarks of aging in this book.
Telomere attrition. Most of us who are any kind of biology and aging geek know
a little bit about telomere attrition, cellular senescence or zombie cells,
mitochondrial dysfunction (the number one theory behind aging). And these hallmarks
are all all have a lot of truth to them. But Sinclair talks about how he's
focused on epigenetics. And sure enough epigenetics has become I think the
reigning perception around how aging happens. What is epigenetics? Well, you've
got DNA, but you've got what six billion base pairs. That's a lot of base pairs to
go in and find and read genes on. So how do you go in and read the genes? Again,
as we get older, we lose the ability to read it. We don't lose the genes
themselves and that's what this is all about. "Epi" meaning
outside genetics, so something outside is reading the genes. So one of the things
that he found early on were things called sirtuins (silent information
regulators), and he discovered those SIRT2 I think in yeast. And that's got a
lot to do with this process. The sirtuins or proteins or enzymes that instruct
histones which in turn are involved in reading our DNA. Bottom line: One of the
things to remember is things that are tightly bound... tightly-bound DNA genes,
they're not just transcribed in loose loops are transcribed. Now, there's an
interesting disease model. It's called Werner syndrome. These kids have
premature aging. These are pictures of them. The preteens appear normal, but
there's a thing, there's a problem with the thing called DNA helicase, something
again that wraps that DNA back into the tight histone and chromosome. It
untangles tangled DNA threads in a pack suit. Now, if you remember on the first
one in my series about David Sinclair's book "Lifespan," we talked about the
demented pianist, where you go to a concert, the pianist is hitting every
note like you should. But all of a sudden he hits a extra note. It doesn't make a
difference. A little bit later, he hits another extra note and another one and
another one. And as the extra notes pile up, it just ends up ruining the concert.
That is the analogy that he uses in this book for the informational theory where
as we age like Werner syndrome patients. We lose the ability to rewrap our DNA, so
the DNA starts spewing throughout the nucleus of the cell. There is no gene
that causes aging, but there's evidently genes that, if they're not functioning,
their malfunction can cause aging. The Werner mutants, for example, are aging
rapidly, and their DNA is madly unpacking "like a vacuum
sealed bag of yarn that had been ripped open in places." So these are called ERC
loops. He started looking at these. He found those in Brewer's yeast. And again,
so now what his team just did was they reversed aging. What they did was they
actually injured the mice at birth. Now
that's cruel and I won't get into animal cruelty and research and things like
that. Point behind it was at birth, we lose the ability in mice due to grow
cells which will go through the optic and optic tract and actually result in
silent. So if mouse loses its sight any time starting with birth, it's not going
to regain it. These mice did... they... how did they how did they regain it? Well, they
used a virus to go back and add a couple of genes that mice don't have after
birth. 3 genes in fact. Expression of Oct4, Sox2, and Kif4 genes (OSK).
They did that, and they changed this whole process. You may have heard of the
methylome. I've got a couple of videos on it over the past couple of years. The
methylome is a... it's part of the DNA clock. Methylation is how the epigenetic
system uses and tags different genes in order to breed them later for filing
purposes. So they basically manipulated the methylome and genes that read the
methylome and resulted in restoration of vision in these mice. They were able to
restore... restoration of vision and mice that had retinal damage from glaucoma. So
again, a lot of very interesting opportunities in terms of future therapy.
And then perhaps an even bigger way of looking at what is it that actually
causes aging, how is it that we read our DNA. Thank you 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 they've 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.