>> I'm Mary Armanios.
I'm trained as a cancer doctor,
as you heard from Steve,
and we've been interested in the consequences of
telomere dysfunction and disease,
and I hope to talk with you about that,
and I think as Carol introduced so nicely,
this is a very timely moment in our field,
and how we talk about this biology in the public sphere,
and in terms of public health.
So the title I have is one that I never expected
when I went to medical school,
to have a title like this,
and I think the title is loaded
in terms of whether,
how is our society thinking about aging,
and why anybody would ever think that
there's a plausible yes to this question,
but with that in mind,
I think I will first talk about
the health implications of telomeres,
and then how we can approach
thinking about this advertising
flood, to the public, especially,
in the past few, few years.
So, when I came to Carol's lab,
there was a lot in the press,
and that I think there still is,
about telomeres and telomerase
being the answer to everything.
If they're too short, they cause aging,
and if we can fix that, we can live forever.
And telomerase is up-regulated in cancer,
and therefore, targeting telomerase
is going to fix all cancers.
Both of those, I think, are not true,
and I'll show you our reasoning for that.
You heard from Carol about
telomerase shortening with age,
and there being a very wide distribution.
This is a first percentile,
and the 99th percentile,
and over the last 10 years or so,
we've been trying to study these folks
who are on the very short end,
and what is wrong with them,
and thinking that if we can study them,
we can really understand what is the contribution
of telomere shortening to aging.
And sorry for this busy slide,
but it turns out that these patients have mutations.
They are born with genetic defects,
and telomerase, the enzyme,
Carol discovered, and other related proteins.
These are fairly rare.
They occur, these mutations occur about
one in 20,000 individuals in the population.
We did not collect 100 of them by screening two million.
We identified these individuals
by virtue of recognizing that they have disease
in our hospital,
and the diseases they have,
some of them are hidden by the sign,
but they have two prominent kinds of diseases.
One is this disease called bone marrow failure.
It affects the integrity of stem cells in their,
in their bone marrow,
and their ability to make blood,
and the other is a disease called,
IPF, Idiopathic Pulmonary Fibrosis,
which is far more common,
and probably many of you might know someone
who has this disease.
So, notably absent from this list
is Alzheimer's, osteoporosis,
and many of the common diseases
that we're gonna talk about,
but these are not, nonetheless,
not that rare, as I hoped to convince you.
And the way that we became interested in this
is through a fairly simple observation.
A patient came to our hospital
who was fairly young.
He was a college student,
and he went gray when he was nine years old.
He did not look otherwise prematurely aged.
But in his family,
all these diseases ran together,
and it turned out that older individuals,
like his grandmother,
this is a pedigree of his family history,
she developed and died from this lung disease,
whereas he had the bone marrow failure problem.
We recently had been working to understand,
if not, and I will tell you upfront,
spoiler alert, doesn't work to predict biological aging,
can we use this medically,
and one of the reasons,
one of the reasons this has been really important
is because when the blood disappears,
this is a picture of a bone marrow,
the way that doctors diagnose bone marrow failure,
and here's a normal, healthy bone marrow.
All the purple spots are cells in our bone marrow
that produce and make blood constantly.
And in these patients with bone marrow failure,
the blood disappears,
but there's two different ways it can disappear.
It can disappear by immune attack,
or it can disappear by a clock mechanism
failing in the stem cells in the blood.
And we were able to show that
we can distinguish these two modes
of bone marrow failure
by measuring telomere length in the blood.
These are the folks that had the immune attack,
and this is the shortening,
the deviation from the median here.
This is the distance of
how short these patients are,
who have this stem cell failure.
If you treat these patients with the same drugs,
as the ones with the immune attack,
they die, actually.
And we found in this study of about 40 patients,
the doctors were able to change their treatment
in a quarter of the time, based on this test.
And this led to our development a few years ago
to figure out how can we make good data,
good telomere length measurement
available to the public,
so we can use this to make decisions
based on long or short telomeres,
in certain subsets of patients.
And we reported these recently,
and I want to just show you some highlights from that study.
One of them is when we measured telomere length
in healthy folks in Baltimore,
and compared them to a healthy control data set in Canada,
we found that they were nearly identical.
Okay? You see here,
there's identical upper and lower boundaries of this,
and I'll point that out, why that's important.
But as we look at the diseases caused by short telomeres,
the disease that's actually far more common
than bone marrow failure
is this disease called pulmonary fibrosis,
which is a distant cousin of
a more common problem in the lung called emphysema,
and these patients develop
progressive scarring in their lung,
but I want to point out that this is
a really under-studied area,
because lung disease is
the third leading cause of death in this country,
and actually, if you think of hair graying
as the manifestation of aging,
there, this scarring is the equivalent
of what happens in the lung.
It's the way the lung ages,
and the telomere seems to be
particular prone to causing that problem.
Now, there was a very large epidemiologic study
published recently, not from our group,
that included data from about 1.5 million people,
and it was a really huge collaborative effort.
And you can't see this,
but these lines go onto the right of one,
and to the left of one.
To the right of one are the diseases
that are caused by long telomeres,
and to the left are the diseases
that are caused by short telomeres.
And if you look here, the disease,
you might be able to see it from the back,
that has the strongest effect size
in this competition of 42 diseases,
is this disease called pulmonary fibrosis.
It's peculiar,
and you would think that if long telomeres
are really good for you,
as the advertising has been trying to claim
and convince the public for,
for I think, commercial reasons,
you would think that on the other end here,
should be longevity, or health span,
or something that we would think as positive,
but instead, it's actually a very increased
risk of cancer,
especially cancer of the lung
and cancer of the skin.
So I think this really tempers the rhetoric
and the conversation,
that the opposite of something we see with aging
is really good,
and highlights what Carol tried to point out,
which is that the middle is really ideal.
So I want to just add a few words
about this commercial testing.
I think there are a few arguments
that suggest it doesn't work.
First, there is a flood of literature
about the testing,
the type of measurement that is used
to offer the public telomere length testing,
to show that it is irreproducible.
This is data from our group.
The clinical measurement I showed you,
if you do it on two different days,
or even across two different labs,
it changes by 2%,
whereas the publicly available testing,
the one that's $99.99 worth,
changes by about a third, by almost 30%.
And the telomere length distribution
doesn't change by that much,
so that is a problem,
and that should be a conversation stopper in the public,
and I've never seen anything
in the scientific literature
that has so much evidence of being irreproducible
still being advertised.
It's really remarkable.
The other point is that there is a threshold,
and Carol pointed this out in her talk,
that there is a threshold for,
in which we see the disease.
And that means that simple telomere shortening,
which happens in all of us,
is probably inconsequential,
and there are probably other,
many other factors that contribute to aging
in a lot of the population,
whereas in this subset of patients,
it does contribute to disease.
And that is a problem when you look at
the type of testing.
So unfortunately, as we have advanced
in our ability to define and make available
clinically meaningful testing
to physicians and to their patients,
there has been this flood,
especially since this company reopened
in the fall of 2016,
and others like it,
that have reached the public in very prominent ways,
including the advertisements during the Super Bowl.
This is a gentleman who lived in Baltimore,
and he, sorry, who lives in DC,
and he's a lawyer, actually, very well-educated,
and he called me and he said that he's decided
to quit his job and sell his house,
based on the results of this direct-to-consumer testing.
He's 39 years old,
but this test told him that he was 80 years old,
and when we measured it,
he's well above the 10th percentile,
from a clinical point of view,
first of all, I wrote clinical here,
because we would have never measured
the telomere length in him.
And here, don't miss this point about what now.
Sorry, the quality's not good,
because there's something,
there's a product being sold here,
there's a claim, there's something to fix this.
So first of all, it's inconsequential, not correct,
and moreover, there's a temptation to sell,
and there is now a market,
unfortunately, for this.
Part of the problem with this has been
that there are elements in the scientific field
that have taken this fairly simple,
two-dimensional way of thinking about aging,
right, this idea that there is a mitotic clock,
or a biological age,
that is somehow more valuable
than some of the things that Janie talked about recently,
which is access to care.
How can we care for the elderly,
how can we have supportive environments,
how can we engage people who retire,
to a focus that's, I feel,
is fairly superficial,
and I hope to convince you of that today.
Now, when these books came out,
early on, we've been talking about them,
and they promote things
like exercise, and healthy eating,
and on some level, those things are not harmful,
and I think we'll hear the themes today,
that those things in and of themselves
are good, for sure, right?
But I do think that this type of conversation,
especially when we talk about aging,
especially when there are so many disparities,
socio-economic and otherwise,
in the care for the elderly,
and in how we view aging psychologically,
that make this a distraction.
Moreover, the fact that long telomeres
have a clear and well-documented cancer risk now
is really alarming to me as a physician,
and suggests that this way of talking about things
is not necessarily the best way.
And the reason I'm, sorry, pausing here,
and this is my last slide,
is that I had this conversation with Dr. Blackburn,
who's the author of this book, recently,
and she told me it's too late to fix this now.
She agrees that the conversation
has gotten out of hand,
and I hope that today, maybe we can think about
trying to talk about these things in a new way,
and maybe it's not too late.
Maybe we can direct conversation and policy,
and community effort around science and aging
in a way that is a bit more nuanced.
So I think with that, I will stop,
and take questions with Carol.
Yeah, thank you.