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