Thank you very much, Dr. King.

It's a pleasure to begin this symposium, I've been

asked to speak about the pathophysiology of feral aging, and as well some of the
manifestations of the photo aging. So on the left is a picture of an individual who
went to Aruba. And this is one single sandbar. On the back, this is a tiny few 23
year old person, you can see where the bathing suit was. And you can see in this
gray Australian the profound damage that can be brought, most probably due to
mutations, multiple mutations and many cell types. Atlanta sites, no doubt chair
tennis sites, which this individual will carry forever. Because it's very, very
likely that that many of these are stem cells. So this is what happens after a
single severe sunburn. In chronic sun exposure, you have a picture that looks like
this, where you have brown spots, you have wrinkles, the wrinkles of the course
sort and this is a fairly good example here. But I chose this mainly to show the
brown spots, because the brown spots are one of the major targets of the retinoid
the treatment. Now, although sun causes major damage in terms of immunosuppression
mutations, certain kinds of skin cancer, the focus of my discussion today is going
to be on the connective tissue. In other words, the extracellular matrix that
brings these types of changes after long term exposure. The left hand side of this
individual's face is worse than the right hand. This is part of the study of
several hundred patients where we showed that the side that is exposed to the
window when you drive has the majority of the sun damage, and people in other parts
of the world have found it to be on the other side of the face, when they drive on
the other side of the road. So it's very, very likely, the final way the most
likely environmental insult would be sunlight. So what how does this come about,
that's really the the subject of my talk today is an ordinary histology slide and,
and the epidemic has been extremely thin order of a 10th of a millimeter, can read
newsprint through it cannot be the source of these wrinkles. You're certainly the
source of various kinds of cancer, but not not, not the wrinkling. And so it's our
belief that the that the major molecule participating here is collagen. And there
are many kinds of collagen, but but 90% of the, of the mass of the dermis is type
one collagen. And so in the other major college in his college, and three, I'm only
going to talk about college and one today, because College in three tracks in terms
of its regulation and changes identically with college in one. So you can just
assume that they're both the same, we do have the data, we have done it. And that
is the way it is. So this is sort of like I guess on this slide is more bluish. But
on a non PowerPoint presentation, you know that it's kind of felt like when you see
it in a microscope, but it's responsible for the form, and the strength and the
function of skin. So this is the major focus of our work, where were the last and
is there. But for a variety of reasons that I've been that I will go into if you
want during the discussion, I can tell you why I don't think elastin is a key part
of what we're talking about. elastin is important to us doses, the yellowish
modular changes and so forth. But remember, what I'm talking about here is the
genesis of Franklin. So collagen for say, is not that easy to measure. So the vast
majority of individuals, ourselves included measure pro college, and we measure
that in various ways. We have a number of techniques that I'll show you. And then
college and once it's formed is degraded into college and fragments, first taken
down by collage into two fragments, three quarters of the length of this molecule
and one quarter, those two fragments. And then gelatinous, will work on those
fragments and take it down to very small pieces. And so one can measure the down
regulation of collagen by either collage and as essays are gelatinous. And there
are various ways of doing that from activity to gene expression, protein content,
etc. And then of course, we can measure college, college and fragments. And once
you see collagen fragments, you know that you had the activity of these two
enzymes.

Now, the point of departure of our work has been really an axiom that you'll have
to agree with otherwise you might as well go out and expose yourself to the sun.
Incidentally, it's a great thing that you're here because about five minutes we
have shown in our early work five minutes. So the kind of son that's outside today
will absolutely definitely kickoff all the biochemistry that I will talk about a
little later.

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