I love collagens... and you should too
[Music]
i
love collagens and i think you should
too
because they are really the key to
understanding and treating
chronic diseases so what is a collagen
to start with i would like to introduce
you a little bit to the importance
and the biology of collagens
so what do you think of when i mention
collagen i think many of you may be
thinking about skin
products we want beautiful skin we want
beautiful collagens
but collagens are so much more than that
they are in fact
the central building block of all
biological structures just like
the eiffel tower where the beams
and the pillars are completely essential
for the structure of the eiffel tower
in fact collagens are the main building
block
of the body and type 1 collagen
is the main protein in the body
and these proteins are the small
building blocks that the entire body is
made of
in addition you might know that we are
made of more than
30 trillion cells and many organs
actually have more of the matter outside
the cells
as compared to the cells this
outside the cells this context is
referred to as
extracellular matrix and this matrix
is critically important for the function
and the behavior of those cells
in fact collagens are the central
component
of this matrix and the cells
they know how to behave because of this
matrix
in fact if we look at cells all cells
have the same dna
they have the same capacity to turn into
a bone cell a brain cell a skin cell or
muscle cell
and the reason why they know how to
behave and what to do
is because of the context because of the
matrix
that they are in so these cells
only know how to function and when to
live or when to die
because of the context they’re in in
fact there are
28 different types of fantastic
qualities
and they are all different in different
organs in different
parts of those organs and and i’m going
to take you through
a few of those so let’s take bone as an
example
type 1 collagen is the main component of
bone
and if we have a lesser quality of
collagen or if we
lose our collagen in bone the bones
break
so at least we need to take care of our
collagen
so i started my my research in bone
more than 20 years ago and this is
actually my
second publication more than 500 have
have come since then
but i didn’t think i realized the
importance of this when i
i first saw this publication in fact
on on this slide you see you see
completely
the same type of cells so the left cells
are on plastic and you can see the black
spots
and they are flat however when those
exact same cells
with the same dna are put in a collagen
gel
they start looking like completely
different cells
these cells look like the bone cells you
saw on a previous slide
and and they start to behave different
so very clearly
the control the form the function
and what these cells are doing so the
collagens control
cells and this is the first premise of
what i’m going to say today
that the matrix what is around the
collagens
they control cells the second part is
we regenerate think of your
body as a construction site there is
demolition and repair ongoing all the
time
in fact we regenerate
so much that the liver can regenerate
if from just 25 of
the remaining liver also
the bones we generate every 10 to 25
years
we actually get new bones and moreover
the intestines actually regenerate every
week
so this construction site where we have
demolition and repair ongoing every day
we need that to be in a perfect balance
if we just have a little bit more
demolition in some organs
we lose that open function and if we
have too much repair
then we have a different disease and
this balance
and this demolition and repair if that
is out of balance
is actually what causing chronic
diseases
in fact this demolition and repair is so
important
and ongoing all the time that you are
not the same self
you are today as you were 9 00 am this
monday morning
so when this balance is out of control
this leads to chronic diseases
chronic diseases are diseases that last
a lifetime and that needs to be managed
in fact
if by the age of over 65
then more than 80 percent of us will
have at least one chronic disease
and what is the common denominator of
these different
diseases it is the collagens have
changed
there are different amounts of collagen
in cancer diabetes
autoimmune diseases with destruction of
the of the bones and in liver diseases
we see in these different
diseases that the collagens have changed
and moreover
we see that the collagens are continuing
to change
for the worse and this means that the
tissue composition
and the coordinates of ireland’s balance
is altered
the repair balance is is disturbed
and this is the central concept
that we are constantly regenerating
and that regeneration leads to that
collagens are broken down
and they are built up and so in this
beautiful slide
you see cells on the top and you see the
structures of collagen below
and so when these tissues
are being remodeled then small collagen
fragments
are being released from the tissue into
the bloodstream
where we can use these as biomarkers
biomarkers are just a simple measurement
just as weight or blood pressure
but it is a objective measurement of a
biological process
and we researchers use them as
biomarkers and we use them every day
so interestingly if if
so many of us have or going to have a
chronic disease
how come we are so bad at treating them
and even curing them well i think it’s
because we are
we are looking at the tip of the iceberg
not what’s life beneath the cells are
only
a small part of what’s going on actually
there’s more matrix
than cells so it is essential to
understand chronic diseases
that we’re not just looking at the cells
but we look at the context
the matrix and the collagens and this is
the second premise
that we regenerate and this generate
collagen
fragments that tells us about the
processes that may lead to chronic
diseases
so let me give you three biological
examples
of what the collagen balance means for
patients
and how important this cottage imbalance
is for patients
and before we go there i want to take a
deep dive into how a collagen truly
looks
because they are unique and fantastic
molecules with a structure
as you can see that is unique for
collagens and they have this structure
so they are they are strong proteins
that are the essential components of all
tissues
so and this is where we have been wrong
all these years we just measured a
protein and collagen
we did not take care in separating the
processes
of tissue demolition and tissue repair
because when we look further at these
collagens it’s very obvious that there
are some fragments that are associated
with repair
and some fragments that are associated
with demolition
so to truly understand which
processes are driving to chronic
diseases
and which processes that we need to
interfere with
to reverse or even cure chronic diseases
or even regenerate organs we need to
understand
the cardiac and threatens
so i’m going to give you three examples
the first one is
bone i started in bone research more
than
24 years ago and and what you see up
here is
is a healthy bone and a bone with
osteoporosis
type one collagen is is the most
abundant protein in bone
and and what you can see is that the
collagens have been lost
in the in the bones that are going to be
fracturing
and so if if we lose collagens then the
bones are going to be fracturing
so we measured the collagen balance in
thousands
of of these individuals and what we
found was amazing
we found that these patients that were
going to have a fracture
and they were losing bone they had more
bone formation
not lower bone formation but more bone
formation
and even more so they had uh and so why
were they
why were they using bone then we
measured the degradation fragments
and it was because that they had even
higher degradation fragments that they
were losing bone
in fact all bone treatments today
are rebalancing this balance all bone
treatments today are either giving you
less bone destruction or more bone
formation
and re-bending in this important balance
so more according fragments we’ve been
looking
into cancer and this has been an amazing
experience
so the premise that we’re not just
measuring the protein
but specific fragments is in particular
true for cancer
so we looked at a collagen and we looked
at two different fragments
one fragment meant that the patients
were going
to die and another fragment of the same
protein
meant that the patients were going to
survive this means that had we just
measured the intact collagen
we would not have known was going to
happen so one fragment
of repair is associated with processes
that are going to make those patients
live and another fragment
is bad processes that are going to make
that patient die
that means that we can can look at those
collagen fragments and we can see
which treatments those patients are
going to be responding to
and this will have an enormous impact on
the life
of of cancer patients
so i want to go to chronic diseases
again
because this is the central premise
there are balances of demolition and
repair
and those balances are resulting in
different fragments of collagens
some that are important for regeneration
and some that are important for
destruction
and in fact in all chronic diseases in
liver disease
lung kidney skin we have seen
that these fragments are altered either
the balance of
repair is a little too much or there is
too much destruction
of tissues and in fact
for all these diseases for liver young
and kidney
we have seen that treatments that are
actually
truly efficacious are changing they call
it imbalance
so for those treatments not just to be
symptomatic
they need to change the call in balance
just as in bone
so this is the third premise really
that collagen fragments is like a
crystal
a biological crystal ball i mean if we
know the cardigan balance
of formation and degradation we can
actually see
if if we’re going to develop a chronic
disease we can see if we are reversing a
chronic disease
and we can see if if patients are
responding
that to a given treatment in chronic
diseases including cancer
so in the end i mean this constant
regeneration and repair means that
we collagen fragments are generated in
the body
all the time some for demolition and
some for repair
in fact during this talk i have i have
generated
more than a billion cells and who tells
the
the cells what to do the collagens do
and those cotton fragments formation and
degradation
allows us to look into the future and
see what’s going to happen
so before i end i just want to thank the
many phd students the postdocs
my directors and all the collaborators
that that through these
last 24 years have have helped us trying
to understand
the biology of collagens and how they
may
help us to change the life of patients
in a completely new way
may the collagens be with you
you