Restoration of Vision Using Epigenetic Methods (by David Sinclair)

Restoration of Vision Using Epigenetic Methods (by David Sinclair)


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.