[House Hearing, 117 Congress]
[From the U.S. Government Publishing Office]
THE FOUNTAIN OF YOUTH?
THE QUEST FOR AGING THERAPIES
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON INVESTIGATIONS
AND OVERSIGHT
OF THE
COMMITTEE ON SCIENCE, SPACE,
AND TECHNOLOGY
OF THE
HOUSE OF REPRESENTATIVES
ONE HUNDRED SEVENTEENTH CONGRESS
SECOND SESSION
__________
SEPTEMBER 15, 2022
__________
Serial No. 117-67
__________
Printed for the use of the Committee on Science, Space, and Technology
[GRAPHIC NOT AVAILABLE IN TIFF FORMAT]
Available via the World Wide Web: http://science.house.gov
___________
U.S. GOVERNMENT PUBLISHING OFFICE
48-487PDF WASHINGTON : 2022
COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY
HON. EDDIE BERNICE JOHNSON, Texas, Chairwoman
ZOE LOFGREN, California FRANK LUCAS, Oklahoma,
SUZANNE BONAMICI, Oregon Ranking Member
AMI BERA, California MO BROOKS, Alabama
HALEY STEVENS, Michigan, BILL POSEY, Florida
Vice Chair RANDY WEBER, Texas
MIKIE SHERRILL, New Jersey BRIAN BABIN, Texas
JAMAAL BOWMAN, New York ANTHONY GONZALEZ, Ohio
MELANIE A. STANSBURY, New Mexico MICHAEL WALTZ, Florida
BRAD SHERMAN, California JAMES R. BAIRD, Indiana
ED PERLMUTTER, Colorado DANIEL WEBSTER, Florida
JERRY McNERNEY, California MIKE GARCIA, California
PAUL TONKO, New York STEPHANIE I. BICE, Oklahoma
BILL FOSTER, Illinois YOUNG KIM, California
DONALD NORCROSS, New Jersey RANDY FEENSTRA, Iowa
DON BEYER, Virginia JAKE LaTURNER, Kansas
SEAN CASTEN, Illinois CARLOS A. GIMENEZ, Florida
CONOR LAMB, Pennsylvania JAY OBERNOLTE, California
DEBORAH ROSS, North Carolina PETER MEIJER, Michigan
GWEN MOORE, Wisconsin JAKE ELLZEY, TEXAS
DAN KILDEE, Michigan MIKE CAREY, OHIO
SUSAN WILD, Pennsylvania
LIZZIE FLETCHER, Texas
VACANCY
------
Subcommittee on Investigations and Oversight
HON. BILL FOSTER, Illinois, Chairman
ED PERLMUTTER, Colorado JAY OBERNOLTE, California,
AMI BERA, California Ranking Member
GWEN MOORE, Wisconsin STEPHANIE I. BICE, Oklahoma
SEAN CASTEN, Illinois MIKE CAREY, OHIO
C O N T E N T S
September 15, 2022
Page
Hearing Charter.................................................. 2
Opening Statements
Statement by Representative Bill Foster, Chairman, Subcommittee
on Investigations and Oversight, Committee on Science, Space,
and Technology, U.S. House of Representatives.................. 7
Written Statement............................................ 8
Statement by Representative Jay Obernolte, Ranking Member,
Subcommittee on Investigations and Oversight, Committee on
Science, Space, and Technology, U.S. House of Representatives.. 10
Written Statement............................................ 10
Written statement by Representative Eddie Bernice Johnson,
Chairwoman, Committee on Science, Space, and Technology, U.S.
House of Representatives....................................... 11
Witnesses:
Dr. Jay Olshansky, Professor of Public Health, University of
Illinois at Chicago
Oral Statement............................................... 12
Written Statement............................................ 15
Dr. Laura Niedernhofer, Director, Institute on the Biology of
Aging and Metabolism; Medical Discovery Team on the Biology of
Aging; Professor, Department of Biochemistry, Molecular Biology
and Biophysics, University of Minnesota
Oral Statement............................................... 29
Written Statement............................................ 31
Dr. Steve Horvath, Principal Investigator, Altos Labs
Oral Statement............................................... 37
Written Statement............................................ 39
Discussion....................................................... 44
Appendix I: Answers to Post-Hearing Questions
Dr. Jay Olshansky, Professor of Public Health, University of
Illinois at Chicago............................................ 58
Dr. Laura Niedernhofer, Director, Institute on the Biology of
Aging and Metabolism; Medical Discovery Team on the Biology of
Aging; Professor, Department of Biochemistry, Molecular Biology
and Biophysics, University of Minnesota........................ 61
Dr. Steve Horvath, Principal Investigator, Altos Labs............ 66
Appendix II: Additional Material for the Record
Letter submitted by Representative Bill Foster, Chairman,
Subcommittee on Investigations and Oversight, Committee on
Science, Space, and Technology, U.S. House of Representatives
The Buck Institute for Research on Aging..................... 70
THE FOUNTAIN OF YOUTH?
THE QUEST FOR AGING THERAPIES
----------
THURSDAY, SEPTEMBER 15, 2022
House of Representatives,
Subcommittee on Investigations and Oversight,
Committee on Science, Space, and Technology,
Washington, D.C.
The Subcommittee met, pursuant to notice, at 10:03 a.m., in
room 2318 of the Rayburn House Office Building, Hon. Bill
Foster [Chairman of the Subcommittee] presiding.
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Chairman Foster. This hearing will now come to order.
Without objection, the Chair is authorized to declare recess at
any time.
Before I deliver my opening remarks, I wanted to note that,
today, the Committee is meeting both in person and virtually.
And I want to announce a couple of reminders to the Members on
the conduct of the hearing. First, Members and staff who are
attending in person may choose to be masked, but it is not a
requirement. However, any individuals with symptoms, a positive
test, or exposure to someone with COVID-19 should wear a mask
while present.
Members who are attending virtually should keep their video
feed on as long as they are present in the hearing. Members are
responsible for their own microphones. Please also keep your
microphones muted unless you are speaking.
And finally, if Members have documents that they wish to
submit for the record, please email them to the Committee
Clerk, whose email address was circulated prior to the hearing.
Well, good morning, and welcome to our Members and our
panelists. One of the most important functions of the Science
Committee is to help inform Congress of rapidly emerging
technologies that will have important policy implications so
that we're not always playing catchup. The past decade has seen
progress in medical technology that would previously have been
seen as science fiction. Not long after its discovery in 2012,
I started getting increasingly urgent requests for meetings
from cellular biologists telling me about the discovery of an
incredible gene-editing technique called CRISPR. And that brave
new world was not going to be a century away and might not even
be a decade.
Many of us were here for the 2015 Science Committee hearing
on the science and ethics of genetically engineered human DNA.
In fact, it was only three years after that, six years after
the discovery of CRISPR, that a Chinese scientist shocked the
world when he announced that he had created the first gene-
edited human child. We are still grappling with the potential
societal, ethical, and economic implications of that
breakthrough.
I believe that the aging therapies being evaluated by the
geroscience community today may be equally seismic in their
impact. The hypothesis at the heart of geroscience is that
aging itself is a relatively small set of general processes,
and that some of them may be malleable. It is a hypothesis that
is reinforced by the wide range of aging processes observed in
the natural kingdom. We didn't use to think of aging as a
disease, but that may be changing. Rather than looking at
individual conditions, the entire process of aging is being
considered as a driving factor behind increasing morbidities.
And because of the analytical tools that have been
developed through decades of federally funded research,
scientists now have the ability to break down aging into a
collection of biological events and are developing a deep
knowledge about how it happens at the cellular level. They are
making connections between these cellular changes and how they
manifest as illnesses and pain throughout our aging bodies.
They're learning that these biological events, at their most
basic level, may be influenced by deliberate or even
inadvertent intervention. And if you can do that safely, aging
and the goal of increasing healthy lifespan, or healthspan, may
come within sight.
In just the past three years or so, scientists have started
testing aging interventions on humans through small FDA- (Food
and Drug Administration-) approved clinical trials. The first
trials had fewer than 100 human subjects, sometimes fewer than
10. But right now, the Albert Einstein College of Medicine,
with the support from the National Institutes of Health (NIH),
is standing up a clinical trial with a cohort of 3,000 subjects
to evaluate whether a prescription drug called metformin can
actually help delay age-related chronic diseases in general. A
formal trial like this that seeks to solve several otherwise
unrelated diseases is relatively unprecedented. Imagine how
profound it would be if we could identify a drug or therapy
that can simultaneously mitigate Alzheimer's, cancers, macular
degeneration, hearing loss, and joint pain with a single or a
small set of treatments. Among those--among other things, this
would have an enormous implication on the Federal budget.
Of course, we're not there yet, this field is still nascent
enough that the leading thinkers are still sorting out some of
the basic vocabulary issues. It seems like almost all of the
serious research efforts are focused on expanding the human
healthspan, not the absolute limit or duration of human life.
We will hear from our witnesses about the concept of
healthspan today, but to be sure, the definition of healthy
varies from person to person. If increasing healthspan is the
goal, how will scientists know that they've done it? And how
can the field determine the success or failure of an aging
intervention without waiting decades to see how people fare as
they age? If every experiment takes 70 years, this field will
take a long time to develop.
If researchers are ultimately successful in translating the
outcomes that they have seen in model organisms into humans, we
will have an even--have even bigger questions to confront. For
example, if you extend healthspan, do you also extend the
lifespan and simply delay the protracted aging process to a
later date? What happens to healthcare costs and the burden of
our healthcare system? Would we see people in their 60's
starting second careers? And what would that mean for the
broader labor force? Can insurance companies charge your--
change your premiums based on whether or not you take the aging
therapy?
So we've all witnessed firsthand the breakneck speed of
technological innovation in the country over the last 40 years,
and so we should know better than to be caught unaware. Our
responsibility as policymakers is to get educated today on a
field of research that could soon lead to transformational
change.
Our witnesses today represent the leading edge of
geroscience, and I know that they will be faithful to the
guidelines on our path to understand this topic and its
implications at a deeper level.
[The prepared statement of Chairman Foster follows:]
Good morning, and welcome to our members and our panelists.
One of the most important functions of the Science
Committee is to help inform Congress of rapidly emerging
technologies that will have important policy implications, so
that we are not always playing catch-up. The past decade has
seen progress in medical technology that would previously have
been seen as science fiction. Not long after its discovery in
2012, I started getting increasingly urgent requests for
meetings from cellular biologists, telling me about the
discovery of an incredible gene editing called CRISPR; and that
Brave New World was not going to be a century away, and might
not even be a decade.
Many of us were here for the 2015 Science Committee hearing
on The Science and Ethics of Genetically Engineered Human DNA.
In fact it was only three years after that--six years after the
discovery of CRISPR--that a Chinese scientist shocked the world
when he announced that he had created the first gene-edited
human child. We are still grappling with the potential
societal, ethical, and economic implications of that
breakthrough.
I believe that the aging therapies being evaluated by the
geroscience community today may be equally seismic in their
impact.
The hypothesis at the heart of geroscience is that aging
itself is a relatively small set of general processes, and that
some of them may be malleable. It is a hypothesis reinforced by
the wide range of aging processes observed in the natural
kingdom.
We didn't used to think of aging as a disease, but that may
be changing. Rather than looking at individual conditions, the
entire process of aging is being considered as the driving
factor behind increasing morbidities. And because of the
analytical tools that have been developed through decades of
federally funded research, scientists now have the ability to
break down aging into a collection of biological events, and
developing deep knowledge about how it happens at the cellular
level. They are making connections between these cellular
changes and how they manifest as illness and pain throughout
our aging bodies.
They're learning that these biological events at their most
basic level may be influenced by deliberate, or even
inadvertent, intervention.
And if you can do that safely, aging and the goal of
increasing healthy lifespan--healthspan--may come within sight.
In just the past three years or so, scientists have started
testing aging interventions on humans through small, FDA-
approved clinical trials. The first trials had fewer than 100
human subjects, sometimes fewer than ten. But right now, the
Albert Einstein College of Medicine, with support from the
National Institutes of Health, is standing up a clinical trial
with a cohort of 3,000 subjects to evaluate whether a
prescription drug called metformin can help delay age-related
chronic diseases in general. A formal trial like this that
seeks to solve for several otherwise-unrelated diseases is
unprecedented.
Imagine how profound it would be to identify a drug or a
therapy that can mitigate Alzheimer's, cancer, macular
degeneration, hearing loss, and joint pain with a single, or a
small set of treatments. Among other things, this would have
enormous implications for the federal budget.
Of course, we are not there yet. This field is still
nascent enough that the leading thinkers are still sorting out
some basic vocabulary issues. It seems that almost all of the
serious research efforts are focused on expanding the human
healthspan, not the absolute limit of the duration of a human
life. We will hear from our witnesses about the concept of
healthspan today. But to be sure, the definition of ``healthy''
varies from person to person. If increasing healthspan is the
goal, how will scientists know they have done it?
And how can the field determine the success or failure or
an aging intervention without waiting for decades to see how
people fare as they age?
If researchers are ultimately successful in translating the
outcomes they have seen in model organisms into humans, we will
have even bigger questions to confront:
If you extend the healthspan, do you also extend
the lifespan and simply delay the protracted aging process to a
later date?
What happens to healthcare costs and the burden
on our health system?
Would we see people in their 60s starting second
careers, and what would that mean for the broader labor force?
Can insurance companies change your premiums
based on whether you take the aging therapy?
We have all witnessed firsthand the breakneck speed of
technology innovation in the country over the last 40 years, so
we should know better than to be caught unaware. Our
responsibility as policymakers is to get smart today on a field
of research that could soon lead to transformational change.
Our witnesses today represent the leading edge of geroscience
and I know they will be faithful guides on our path to
understanding this topic at a deeper level.
I thank them for joining us today and I yield to Ranking
Member Obernolte.
Chairman Foster. I now request unanimous consent to include
in the record for this hearing a letter from the Buck Institute
for Research on Aging, and without objection, so ordered.
And the Chair will now recognize the Ranking Member of the
Subcommittee on Investigations and Oversight, Mr. Obernolte,
for an opening statement.
Mr. Obernolte. Thank you, Mr. Chairman. I am so excited
about this hearing. I'm excited for a number of different
reasons. For thousands of years, mankind has been searching for
the fountain of youth. And in the last several hundred years,
it has become abundantly clear that the fountain of youth is--
is going to be discovered not through exploration, but through
science.
It is a particularly relevant topic for this Subcommittee
to be taking up for several reasons. First of all, the fact
that a lot of the research in geroscience is funded through the
NIH and the NSF (National Science Foundation), which are
governmental agencies that we have influence over, so it'll be
very interesting to me to see some of the fruits of that
investment. And that will better prepare us to make the
argument for continued investment and maybe greater investment
in the future.
But I am also interested because, as the Chairman
mentioned, the implications of a longer human lifespan are
profound in the fields of public policy and governance, both
good and bad. And it behooves us to start having that
conversation early as we prepare for the societal changes that
will come as a result of a greater life expectancy in the
United States.
But the third reason that I am so excited about this is
because, in many ways, you can judge our progress as a society
and a country by our average life expectancy. It's an
indication not only of our prosperity, but also of the ways
that we honor and treat our elderly. And if we can catalyze a
future life expectancy and a future growth in life--in
healthspan, the number of years that we have a productive,
healthy living, we will progress not only as Americans but also
as a human race. So I'm very excited to hear from our witnesses
and very excited that this hearing has been convened.
Thank you, Mr. Chairman. I yield back.
[The prepared statement of Mr. Obernolte follows:]
Good morning. Thank you, Chairman Foster, for convening
this hearing. And thanks to our witnesses for appearing before
us today.
Aging is an inevitable occurrence for those of us lucky
enough to live long enough to experience it. Since the
phenomenon of aging began, humans have been exploring ways to
slow down the effects of aging and extend human lifespan. This
anti-aging mentality has strong roots in our culture--just look
at the variety of skincare products on the market today or the
title of this hearing. Throughout history, humans have always
been seeking the ``fountain of youth''.
What we have convened to discuss with our witnesses today,
though, is not how we can end the aging of human beings, but
how we can extend collectively the period of healthy living, or
health span. This means not necessarily extending the lifespan
but extending healthy life before aging related diseases are
able to take hold. If achievable, this could have huge
implications on society, as the physical and mental effects of
aging are slowed, and we are able to live healthy lives for a
longer time.
Our witnesses today represent a variety of stakeholders who
have been engaged on this topic in the scientific community.
One common theme I have found from their testimony is their
emphasis that geroscience, the science of aging research, is
not focused on expansively extending human life to immortality.
Rather, they are utilizing a number of scientific methods and
techniques to uncover treatments that could generally slow the
effects of aging and prevent the prevalence of disease in older
generations as they age. The research they are doing ranges
from the reversal of aging to isolating senescent cells to
preventative therapeutics that can have across the board health
implications.
I am looking forward to hearing more about these different
therapeutics and treatments, but also about how traditional
methods of living a healthy life by practicing good diet and
exercise habits can play into this equation.
Federal investment into geroscience research has primarily
been at the National Institutes of Health. In 1974, NIH
established the National Institute of Aging to fund research
focused on the effects of aging and examine the issue in depth.
The National Science Foundation has also awarded grants focused
on the study of senescent cells and biological factors that
contribute towards aging. Additionally, I would be remiss to
leave out the huge amounts of private sector capital that has
been invested into aging research.
Aging is a topic that interests us all, as we all hope to
live long and full lives. It is an interesting perspective to
consider that this challenge of aging is really a challenge
born from the success of living longer lives.
Thank you, Chairman Foster, for convening this hearing. And
thanks again to our witnesses for appearing before us today. I
look forward to our discussion.
I yield back the balance of my time.
Chairman Foster. Thank you. And if there are Members who
wish to submit additional opening statements, your statements
will be added to the record at this point.
[The prepared statement of Chairwoman Johnson follows:]
Good morning.
Thank you, Chairman Foster, for holding today's hearing on
geroscience, a field with the potential to transform our
society. A field which challenges what many have assumed is a
universal truth--that aging is immutable.
The significance of what we will be discussing at this
hearing cannot be overstated. I had a twenty-year career as a
nurse, and from that experience, I know firsthand the
challenges of compounding illnesses in seniors--on both the
patient and on our health care systems.
I like to say that the Science, Space, and Technology
Committee is the committee of the future. Today's discussion is
just one more chapter in the Science Committee legacy of
looking over the horizon:
In the mid-1970s, under Chairman Olin Teague of Texas, the
Science Committee held the first hearings on the threat of
climate change.
In 1979, the Committee under Chairman Don Fuqua of Florida
took the first look at the opportunities and risks associated
with technology transfer to China.
In 2010, Chairman Gordon of Tennessee led hearings on
geoengineering, where the very notion of carbon removal was
first introduced to Congress. Now, twelve years later, we have
provided $3.5 billion dollars to the Department of Energy
through the Infrastructure Investment and Jobs Act in order to
stand up technology hubs for direct air capture.
Those previous hearings were important because they
provided an opportunity to start needed public discourse on
critical issues, no matter how futuristic they might appear. As
one ancient Greek philosopher said, ``the only constant in life
is change.'' We need to be prepared for those changes.
If geroscience succeeds in its grandest promises, there
will be a host of ethical questions to consider. This hearing
gives us a chance to examine some of those questions. It also
gives us the chance to set the stage for a productive and
positive conversation on aging. For too long, aging has been a
negative word or something to fear. However, we all age. We
cannot stop time. I am pleased that the consensus in the
scientific community is that we don't need to chase
immortality. What we need to do is increase our healthy years
and mitigate the health concerns brought on by age. And we need
to ensure equal and affordable access to the tools and
therapeutics that increase everyone's healthspan.
On the wall on our hearing room in the Rayburn Building is
a quote from Alfred Lord Tennyson:
``For I dipped into the future,
Far as human eye could see,
``Saw the vision of the world,
And all the wonder that would be.''
I am proud that today's hearing will once again dip into
the future and try to see a vision of what's to come.
I yield back.
Chairman Foster. And at this time, I'd like to introduce
our witnesses. Our first witness is Dr. Jay Olshansky. And Dr.
Olshansky is a Professor in the School of Public Health at the
University of Illinois at Chicago, Research Associate at the
Center on Aging of the University of Chicago, and Chief
Scientist at Lapetus Solutions, Incorporated, a company he
cofounded. Dr. Olshansky's work is focused on linking the
scientific study of aging with investments in longevity and
mortality-related projects--products. Additionally, his
research includes exploring the health and public policy
implications associated with individual and population aging.
Dr. Olshansky is also a board member of the American Federation
for Aging Research.
After Dr. Olshansky is Dr. Laura Niedernhofer. I hope I did
that right. OK, thank you. Dr. Niedernhofer is a Director of
the Institute of the Biology and Aging and Metabolism and
Medical Discovery Team on the Biology of Aging. She is also a
Professor in the Department of Biochemistry, Molecular Biology,
and Biophysics at the University of Minnesota. Her research
program is centered on the--studying fundamental mechanisms of
aging and developing therapeutics to target them. She's also
contributed to the discovery of a new class of drugs called
senolytics. Dr. Niedernhofer currently serves on the Advisory
Council of the Division of Aging Biology at NIA (National
Institute on Aging) and on the Board of Directors of the
American Federation for Aging Research.
Our final witness is Dr. Steve Horvath. Dr. Horvath is a
Principal Investigator at Altos Labs and a tenured full
Professor in Human Genetics and Biostatistics at the University
of California, Los Angeles (UCLA). His research lies at the
intersection of several fields, including epigenetic biomarkers
of aging, preclinical and clinical studies in genomics and
epidemiology. Dr. Horvath and his UCLA colleagues published the
first epigenetic clock for saliva in 2011 and 2013. And he
published the first pan-tissue clock, also known as the Horvath
Clock. Recently, he presented a universal clock that measures
age in all mammalian species. Great, OK.
And now as our witnesses should know, each of you will have
five minutes for your spoken testimony. Your written testimony
will be included in the record in its entirety. And you--when
you have all completed your spoken testimony, we will begin
with questions. Each Member will have five minutes to question
the panel. And if we have time, we may have a second round of
questions this morning.
And we'll start with Dr. Olshansky.
TESTIMONY OF DR. JAY OLSHANSKY,
PROFESSOR OF PUBLIC HEALTH,
UNIVERSITY OF ILLINOIS AT CHICAGO
Dr. Olshansky. All right. First of all, I want to thank the
Committee for the opportunity to participate in these hearings
on what I consider a new public health initiative within--known
within the community of scientists and health professionals as
geroscience. The story I'm about to tell you is an easy one to
communicate because all of us are experiencing aging firsthand.
In the modern era, most people in developed nations and a
rising percentage of people in developing nations have the
privilege of living a long life, a privilege denied to most
throughout history. Pioneers in public health medicine and
science from just a few generations ago gave us the gift of a
long life. And since then, humanity has worked hard to maintain
this privilege and extend it to others less fortunate.
Life expectancy increased from one year every one or two
centuries for the previous several thousand years to three
years of life added per decade in the 20th century. The chances
of surviving to the age of 65, 85, and 100 have never been
higher than they are now. There is reason to declare victory in
the pursuit of extended survival, but plenty of work remains to
ensure this privilege is made available to everyone.
This longevity revolution came with a price. The modern
rise of cardiovascular diseases, cancer, dementia, Alzheimer's,
and nonfatal impairments are byproducts of success, not
failure. We just had to live long enough to see them. While
risk factors hasten the emergence and worsening of these
diseases, the biological processes of aging march on in the
background, uninfluenced by treatments for diseases. Aging has
become the most important risk factor for the diseases and
disorders that occur today.
The quest for aging therapies discussed in this hearing is
at the heart of a new public health paradigm that has been in
the works for the last half century but which has gained
traction just within the last few years. Here's the story in
brief.
Changes in our cells and tissues occur with the passage of
time. We call it aging. But there's nothing magical about this
since we see the same process occurring in our pets and
automobiles. It was suggested in the 1950's, 1960's, and 1970's
that aging should eventually become the target of medicine and
science, but too little was known at the time about how aging
happens. Medicine and public health did what it could in the
interim to devise ways to detect and treat diseases one at a
time as if independent of each other. And this was a logical
next step in dealing with the diseases that appear in aging
bodies. But this approach came with limitations that can best
be thought of as a game of Whac-a-Mole. Knock one disease down
and another appears shortly thereafter. The longer we live, the
shorter the distance between these diseases.
The science behind the ``how'' question in aging has
advanced rapidly, which now makes it possible to pursue the
gold standard in public health, which is to slow down aging
itself rather than just treat its consequences. Geroscience has
come of age. It is the culmination of decades of research. It
is not a theoretical construct. It has been demonstrated in the
laboratory, that rate of aging can be modified in other
species, which means rate control is possible in humans.
The first clinical trials of aging therapeutics, known as
geroprotectors, are already underway, and the FDA is fully on
board with this approach, which is to prevent disease by
slowing aging. The health and economic benefits of geroscience
will be substantial. A cure for cancer would be welcomed, but
that's just one disease of many that plague older bodies, and a
cure for cancer would only add about three years to life
expectancy. A geroprotector will simultaneously lower the risk
of all fatal and disabling diseases of aging simultaneously,
which means even a modest effect would yield amplified health
benefits. The cost savings in healthcare alone would amount to
over $38 trillion for each year of life generated with
geroprotectors.
The primary goal of geroscience is the extension of
healthspan, not lifespan. So these advances will not generate a
fountain of youth in the colloquial sense, but it will
fundamentally change what it means to grow old. We will remain
younger longer, retain our youthful vigor for an extended
period of time, and compress everything we don't like about
aging into a shorter duration of time at the end of life.
There will be challenges that accompany the generation of a
healthier and more robust older population, but the most
precious commodity that we cherish most, our health, will be
the gift of geroscience. It's difficult to imagine any scenario
in the future where the generation of a larger healthy older
population would not be pursued, even if challenges appear
along the way.
This is just an introduction to geroscience, and I'd be
happy to take any questions you may have. And thank you once
again for the privilege of participating in this hearing. My
written testimony will address all of these issues in far
greater detail. Thank you very much.
[The prepared statement of Dr. Olshansky follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Chairman Foster. Thank you. And next is Dr. Niedernhofer.
Whoops, I think you're muted.
TESTIMONY OF DR. LAURA NIEDERNHOFER, DIRECTOR,
INSTITUTE ON THE BIOLOGY OF AGING AND METABOLISM;
MEDICAL DISCOVERY TEAM ON THE BIOLOGY OF AGING;
PROFESSOR, DEPARTMENT OF BIOCHEMISTRY,
MOLECULAR BIOLOGY AND BIOPHYSICS,
UNIVERSITY OF MINNESOTA
Dr. Niedernhofer. Good morning, and thank you very much for
this opportunity to participate.
So geroscience refers to the fact that advanced chronologic
age is the greatest risk factor for most diseases. Therefore,
developing therapeutics that disrupt the biologic changes that
universally occur with advanced chronologic age is not only
logical, but potentially highly impactful to human health. A
geroscience approach is anticipated to impact the health of the
elderly to a greater extent than curing any single disease of
old age, and this includes Alzheimer's disease or cancer.
Importantly, geroscience aims to extend how long individuals
are healthy, not how long they live, what we refer to as
extending healthspan.
So geroscience is based on three facts. First, we are in an
unprecedented period of human history in which the number of
elderly is doubling and surpassing the number of young people.
This establishes the need for a new approach to prevent our
healthcare system from becoming overwhelmed and healthcare
costs from skyrocketing. Second, the majority of people over
the age of 65 have two or more chronic diseases. Hence, curing
a single disease of old age will not dramatically improve the
health of the elderly. Third, chronologic age contributes to
the risk of most diseases to a much greater extent than other
risk factors that we are currently treating. Thus, therapeutics
targeting aging biology have the potential to be not only
useful for many diverse diseases, but also to be highly
effective at doing so compared to our current first-line
treatments.
So today, geroscience is--where it stands is there is ample
evidence that certain molecular and cellular events occur in
most if not all people with advanced chronologic age. There's
also ample evidence that some of these events can be
therapeutically targeted in humans, as well as in disease
models. We have in hand FDA-approved drugs that target and stop
or even reverse these molecular and cellular events of aging
biology. We also have extensive data from animal models, what
we call preclinical data, demonstrating that geroscience-guided
therapies prevent, attenuate, or even reverse age-related
diseases, affecting most organ systems. This includes heart
disease, Alzheimer's disease, and diabetes. There exists at
least one drug mentioned, metformin, that appears to
simultaneously stave off diabetes, heart disease, cancer, and
cognitive impairment. There are also numerous other tentative
geroscience drugs already approved by the FDA and in clinical
use that should be tested for geroscience approaches. There's a
lot of activity in the space of developing therapeutic
interventions that target aging biology, primarily in academic
centers at this point but gaining traction in the
pharmaceutical industry.
So what I perceive as key barriers to progress are adequate
funding to pursue geroscience research in a timely fashion,
lack of physician scientists and infrastructure needed to
support clinical trials in geriatric patients, lack of public
knowledge about geroscience, and a lack of biomarkers that
report how well an individual is aging relative to just using
their chronological age, as we do now.
The Federal Government could facilitate geroscience
research by providing Federal funding dedicated to supporting
geroscience research across many disciplines; support for
training physician scientists knowledgeable about clinical
trials in geriatric patients; funding and support to create the
infrastructure needed to advance geroscience research,
including sharing of biospecimen and data; and facilitating the
collection as well as the dissemination of information across
diverse race, ethnic, and socioeconomic groups.
So what would be the societal implications? Well, although
this is really not my area of expertise, I can offer my
opinion. Aging biology affects virtually every aspect of how an
individual interacts with their world, communication,
transportation, housing needs, healthcare needs. The elderly
exit the work force while requiring significantly more help. As
a number of chronologically aged individuals continues to
increase, we as a society will have to accommodate all of these
changes. Geroscience, though, offers an alternative approach
where we aim to keep those of advanced chronologic age healthy,
independent, active, able to work if they choose, and able to
contribute to the economy.
Given the wealth of scientific evidence supporting
geroscience, I feel it would be irresponsible not to try this
alternative. I personally cared for four parents and
grandparents over the last few decades, each of whom had
multiple diseases of old age, and I can attest it's time-
consuming, costly, heartbreaking, but also robbing younger
individuals of productively contributing to society.
Thank you very much.
[The prepared statement of Dr. Niedernhofer follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Chairman Foster. Thank you. And as someone who shared the
experience you just mentioned with his own parents, this is--
it's an important thing to--so the aggregate quality of life of
being a human.
And finally, we have Dr. Horvath.
TESTIMONY OF DR. STEVE HORVATH,
PRINCIPAL INVESTIGATOR, ALTOS LABS
Dr. Horvath. Yes, my name is Steve Horvath. I'm testifying
in my personal capacity as a scientist. I'm very honored to
speak to the Members of this Committee today.
I would like to speak to you about a new class of molecular
biomarkers known as epigenetic clocks, which allow us to
measure aging in all mammalian cells, tissues, and organs. Epi
means above, and it relates to how epigenetics or methylation
controls which genes are turned on or off. Building on work
following the Human Genome Project, we now understand that your
DNA alone is not your destiny. Epigenetics can drive change in
your cells. And importantly, it is believed that many of these
epigenetic changes may be modifiable. Many researchers believe
that emerging work in epigenetics may be critical for the
development of more personalized medicines.
An epigenetic clock is a biochemical test that is based on
DNA methylation, which are chemical modifications of the DNA
molecule. We now can reliably measure human age using a simple
blood draw. By applying epigenetic clocks to DNA collected
before and after a drug treatment, we're able to quickly
determine if a drug is affecting the epigenetic aging process.
Using these epigenetic clocks, we and others have found
interventions that greatly reversed age of mice and rats. Some
of these results are expected to matter for human health as
well.
In 2019, Greg Fahy and I published results from a phase 1
human clinical trial that demonstrated a notable first, that a
treatment consisting of already-approved drugs and supplements
could reverse all established epigenetic clocks in healthy
older men aged between 50 and 65. In a current phase 2 trial
known as TRIIM-X, which is going on in California right now, we
will assess if this same treatment can be applied to women and
men between 40 and 80. The trial may also determine if the
treatment leads to functional improvements in older individuals
such as increased leg strength that will delay onset of
frailty.
This ongoing work has provided a helpful template for the
longevity research community. When used along with standard
clinical and physiological testing, epigenetic clocks could add
a rigorous and practical approach for determining if a new
longevity drug is effective for use in healthy, older
individuals. Preventative medicine trials that previously took
many years may now be completed in only one to two years,
although tracking of longer-term health outcomes will be
critical as well.
The biotech industry is also now developing exciting new
drugs targeting the biology of aging. As the data mature, there
will be a need for a clear regulatory framework for drug
approval in healthy, older individuals. In addition, looking at
current disease classifications to ensure they are inclusive of
these new therapies would be very helpful. My hope is that this
Committee and others in government will recognize the recent
biomedical breakthroughs, including biomarkers of aging, and
modernize the approval process for new longevity treatments. We
have an opportunity and arguably an obligation to leverage
these recent biomedical breakthroughs to identify interventions
that may delay the onset of chronic diseases and which may
revolutionize the field of preventative medicine.
When we look back at past centuries, we find the high rate
of child mortality completely unacceptable. Nearly 50 percent
of babies born in the U.S. in 1800 did not live past their
fifth birthday. I predict that future generations will look
back at our times and recoil in horror at the high mortality
rate in the elderly. Globally, over 100,000 people die each day
due to age-related diseases. We don't have to accept this
anymore.
Thank you for your time and invitation to speak to you.
[The prepared statement of Dr. Horvath follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Chairman Foster. Thank you. And at this point, we will now
begin our first round of questions, and the Chair will
recognize himself for five minutes.
Dr. Niedernhofer, there seem to be at least three active
subfields of research here. There's cellular senescence, cell
reprogramming, and thymic rejuvenation. There are probably
others. Could you please briefly explain a bit about the status
and goals of each of these and other approaches, beginning with
senescent cells if you--since you're one of the experts on
that? And might you shoot for three minutes?
Dr. Niedernhofer. Well, thank you very much for this
question. What the field has done, it has recognized what we
call hallmarks of aging. So these are sort of the universal
processes that seem to happen in every organism from worm
models to rodents, primates, humans. And these are all
candidate targets for therapeutics. Senescent cells have
emerged as one of those targets or hallmarks of aging that is
very, very tractable, so this allows us to develop therapeutic
drugs that target senescent cells.
The reason this is important is senescent cells are cells
that are stressed, they've responded to that stress in our
body, which is a very healthy thing to do. It suppresses
cancer, but afterwards, the cells linger chronically and they
secrete things into their environment, which are very
proinflammatory. And it's quite clear that senescent cells at
this point promote aging, as well as contribute to virtually
every age-related disease. And so if we can clear them with
drugs, help the body and the immune system clear them, we
really see a tremendous impact of this approach.
Reprogramming is a little bit different, where you're
trying to rejuvenate through epigenetic changes, as Dr. Horvath
has spoken about, to rejuvenate the cells rather than get rid
of damaged cells. So this holds a lot of promise as well.
There's lots of other approaches, rejuvenating stem cells,
improving the response to genome instability, nutritional
stress, and the response to nutrients. So we have lots of
different opportunities here to target biology of aging, and I
think they're all coming together quite nicely.
A very important point to make is all of these hallmarks of
aging are truly interrelated, meaning if we target any one of
them, we can actually improve multiple of these hallmarks of
aging and literally remove damaged cells or rejuvenate existing
ones. And so there's a lot of promise here. Thank you.
Chairman Foster. Thank you. And, yes, I was struck by a
study that you co-authored where healthy adult mice were dosed
with extra senescent cells. And so can you just describe
quickly what was the result of the senescent cells?
Dr. Niedernhofer. Yes, that's a great question. So what's
really important to prove cause and effect, which has been
extremely challenging in the field of biology of aging, we have
these hallmarks of aging, but do they really cause aging? So
what you have to do is add senescent cells if you want to test
the hypothesis that they drive aging, or take them away. And so
we have dosed animals with extra burdens of senescent cells,
and the impact on those animals are they have reduced
spontaneous activity, reduced grip, and altered metabolism. So
all of the things that we observe with normal aging is--can be
driven by the transplantation of senescent cells into a model
organism. And in fact, one of our studies showed that senescent
immune cells are one of the most potent ways to drive aging of
all of the tissues in your body.
So we also have very strong pharmacologic as well as
genetic evidence that if you remove senescent cells, you can
regain the spontaneous activity, the grip strength, the
endurance, so all of these things that we really are passionate
about and lose as we become more frail with old age.
Chairman Foster. Yes, thank you. And I find these senescent
cells fascinating, just the--you know, the concept that there
are these cells, they're not dead yet, but they're not doing
their job. You know, until recently, it actually reminded me
very much of the U.S. Senate. But it's not the subject of this
hearing.
Anyway, well, let's see. I guess I am close enough to the
end of my time, and I'll turn it over to the Ranking Member.
Mr. Obernolte. I'll second the sentiment about the Senate.
Thank you very much to our witnesses. It's been a really
interesting hearing.
Dr. Olshansky, I'd like to start with you. I was very
interested in both your oral and written testimony where you
talked about the potential cost savings of $38 trillion a year
per year of extended lifespan? Could you talk a little bit
about in that analysis how you came up with that number?
Dr. Olshansky. Actually, I didn't come up with that number.
That was research that was done by some of our colleagues in
the UK, some scientists at Harvard. That's a much longer story
that I'm--and I'm not the expert on having come up with the $38
trillion estimate. So I'm actually going to leave that question
to the scientists that generated that research, but I'd be
happy to send the citation or provide that citation to anyone
who wants it. But----
Mr. Obernolte. OK, well, let's talk about the potential
other side of that equation, which, you know, you talked about
how currently that dealing with aging is like playing Whac-a-
Mole and that perhaps one of the--in your written testimony,
you said perhaps one of the breakthroughs in geroscience would
be disease compression where, you know, we're compressing the
period of our lives that we're experiencing these. But, you
know, what if it's somewhere in the middle where we're just--we
just get really good at whacking the moles right as we move
along. And--but in that case, you would actually achieve a
greater human lifespan but at much greater cost. And actually,
I mean, that's kind of what we've been experiencing so far with
our--our healthcare system, right? This is--as a society, we've
been really grappling with this issue of how to equitably
distribute those costs because it's great that we have these
greater lifespans, but you know, the treatments are becoming
increasingly more expensive. So you know, what--why is--let me
ask you to defend why you think it's a cost savings and not an
increased cost, you know, given the fact that either one would
be preferable to what we've got now?
Dr. Olshansky. Yes, so, several years ago, in 2018, I
published an article in the Journal of the American Medical
Association entitled ``From Lifespan to Healthspan.'' And in
there, I describe what we've done to ourselves. We basically in
the 20th century redistributed death from the young to the old.
We've extended survival very effectively past the ages of 65
and 85. But we've done it against the backdrop of one of
frailty and disability that rises exponentially with
chronological age. I refer to that as the red zone, a time
period where if you live into this red zone, frailty and
disability is extremely high.
If we continue along the pathway of attacking one disease
at a time, in all likelihood, we will succeed in extending
survival deeper and deeper into the red zone, which would raise
costs per capita, would raise overall costs associated with
healthcare. There would be a pretty heavy price to pay if we
continue along the current path.
The focus of geroscience is not on the line that pushes us
toward later ages. It's on the red zone itself. It's to
compress the red zone, push it to later ages so that when bad
things happen that are associated with aging, they happen over
a much shorter time period. And all the costs associated with
that--with end-of-life care and end-of-life health issues would
be less costly and compressed over a shorter time period. And
that is the kind of thing that we're seeing in the animal
models is compression of morbidity, not just lifespan
extension.
Mr. Obernolte. Thank you. Dr. Niedernhofer, I had a
question for you. I thought it was really interesting when you
were talking about the societal implications of a greater
lifespan. And you were careful to say this isn't your field of
expertise, but I'm wondering your thoughts on--on some of the
negative consequences. Because if you take the limiting case
where human lifespan is greatly extended, then you get into a
situation where every single birth adds to the population of
the planet. So, I mean, what are the ethical implications of
that? Because that would seem to be something that also society
would struggle to deal with?
Dr. Niedernhofer. It's a great question, but I would really
like to emphasize that our goal is to make the elderly more
healthy, making them more useful so they're able to work,
contribute, spend their money, vacation, do all those things
that we really enjoy. So I don't see a negative consequence of
this. Keeping people healthy, active, more useful I think is
all good for the economy. But I am not an expert.
Mr. Obernolte. Sure. Well, I mean, it's--obviously, this is
something that we should do it need to do. But, I mean, we also
need to be realistic about the societal implications of it. All
right. Well, thank you very much. I see my time is expired. I
yield back, Mr. Chairman.
Chairman Foster. Thank you. And we will now recognize
Representative Perlmutter for five minutes.
Mr. Perlmutter. Thanks, Mr. Chair. And this--maybe as I'm
getting older, this is a very fascinating hearing we're having
today. And I--you know, we just had to move my mom into memory
care.
So, Dr. Horvath, I want to start with you. In terms of your
biomarkers and your ability--the ability that's being developed
to look at things across the board, so cardiovascular or cancer
or, you know, brain diseases, so as somebody develops
Alzheimer's, I mean, how--are you seeing things that might help
us reverse something like that? Because going back to Mr.
Obernolte's questions, we see sort of on a macro basis just
huge cost to society, particularly from Alzheimer's. So can you
sort of respond to that for me?
Dr. Horvath. Yes. When it comes to Alzheimer's disease, I
do see exciting results, certainly in basic research. I'm just
at a conference here, and I see wonderful, very promising
talks. We really understand a lot about Alzheimer's disease. As
our knowledge increases, we will undoubtedly develop effective
medicines. I'm just as sure as you can be. The question is how
fast. There is always a chance of serendipity, you know, but
I'm very happy to hear that there are ongoing clinical trials.
And what I can tell you, Alzheimer's disease, of course,
it's to--protein aggregation, so called proteostasis, but also
many other facets of aging that touch it, the immune system,
also epigenetic changes, changes in garbage removal, autophagy
in the cells. And so--and there's really an army of researchers
working on it, on all of these facets. And the same of course
pertains to other diseases.
Mr. Perlmutter. So the other panelist is saying, look, if
we are able to, through geroscience, start affecting how cells
age, I assume that this would, you know, as a general
principle, help slow down the potential for an Alzheimer's or
that kind of disease? I mean, are you seeing that in your
research?
Dr. Horvath. Yes. The idea is make cells more resilient.
Young cells are resilient. They can tolerate various forms of
stress. And so, yes, I think that's a very promising avenue.
Mr. Perlmutter. Thank you. I'd like to--you know, our
problem as legislators is to figure out what are going to be
the macro results of this, you know, what are the consequences?
And, Dr. Niedernhofer, you started to opine on that a little
bit. I mean, I think the good news is if we're successful
here--you know, I'm--I think you're probably right that we
would have independent, productive, you know, happy people. You
know, and that's my goal as a legislator, to improve society.
So kind of give us what you think might be some of the problems
that we as legislators would face if you as doctors and
scientists are successful.
Dr. Niedernhofer. Problems that we would face? I think it
would help solve a lot of problems. I mean, one example I'd
like to give to you is think about centenarians. So it's a fact
that they experienced 20-plus years of healthy living. And in
the last two and a half years of their life, they use the
healthcare system much less. They're not sick, they're not
going to doctors, they're not taking as many medicines. And so
biology tells us we can be fit, healthy, less frail in old age.
Picture Queen Elizabeth. I think she was a beautiful example.
She's working, she's on vacation, and then she just has this
very compressed period of morbidity. So I look at this as an
opportunity to solve problems.
Mr. Perlmutter. Thank you. I'll yield back to the Chair. I
think we'll get to do a second round, so I just need to digest
all of this that you people are talking about. We--I would say
one thing. We had a Governor in Colorado, Dick Lamm, who was
called Governor Gloom, some of you may remember, because he
said everybody had a duty to die and so that we didn't put
extra pressure and costly pressure on the healthcare system.
And you're saying that if this is successful, we're going to do
just the opposite, so I appreciate that. I yield back to the
Chair.
Chairman Foster. Thank you. And we'll now--let's see. Is
Representative Beyer still on the call? He was due up next, but
if--he is apparently not here. All right. In that case, I think
we'll start our second round.
You know, and so--let's--I was caught a little bit unawares
here. What are the major Federal players in funding anti-aging
research right now? You know, I'm aware that the National--
well, the National Academies have been ongoing for a while. The
National Science Foundation has a--an effort going on. And so
what are the major players both nationally and internationally
in this? Dr. Niedernhofer, do you want to take a swing at that?
Dr. Niedernhofer. Sure. So definitely the National
Institutes of Health, in particular, the National Institutes on
Aging. I would also give credit to NCI (National Cancer
Institute), the Cancer Institute. They are thinking deeply
about the interface of cancer and aging, as well as other
institutes within NIH. The National Academy of Medicine has
been very forthcoming in tackling aging. They've just written
an incredible geroscience white paper that's available
publicly. We see a lot of philanthropies trying to get
involved. And I should also point out that the Office of the
Director at NIH is investing in a lot of related projects
analogous to the Human Genome but more focused on aging. So for
instance, the SenNet Consortium that's addressing senescent
cells, trying to characterize them so we can ultimately develop
better therapeutics targeting them. So I think there's a lot of
opportunity. I think what's really important for legislators is
to keep this democratized so this is not something that's just
swept away by wealthy individuals but instead, we learn about
the biology of aging across very diverse groups of individuals
so that everybody can benefit from this research.
Chairman Foster. Yes. Are the majority of these candidate
drugs involved as senolytics, are these small molecule off-
patent drugs that are likely to be fairly cheap to provide, or
are there--they're going to be very--any feeling on how
expensive these would be?
Dr. Niedernhofer. That is a great question. So right now,
we have largely in the field, particularly in academics taking
financial support from Federal funding for our research, we've
really focused on natural products, as well as repurposing
existing drugs. And they're--the main rationale for that is
these are going to be faster to test in a clinical setting
because they--we can jump right in with a phase 2 clinical
trial and not have to start from ground zero where we're just
proving safety. So this is speaking to the urgency that we
recognize. They are relatively inexpensive because these are
either drugs that are FDA-approved but not prescribed or off
patent, or natural products that are relatively inexpensive.
So the one I can provide actual numbers on is we've been
working with Fisetin. It's advanced at clinical trials. It's
about $15 a dose, and you need two doses every two weeks, so
quite inexpensive.
Chairman Foster. Yes, because one of the things that we
wrestled with policy-wise is that they're--you know, for a drug
which is off patent, there's very little commercial incentive
to go and pay for the clinical trials. I was just wondering if
that's something where we're actually just going to need
government money to make sure the promising drugs are carried
through to clinical trials because the absence of a commercial
incentive.
Dr. Niedernhofer. I do think it would be the responsibility
of the Federal Government to get this started. I think it's
also really important to de-risk this approach. As Dr. Horvath
was saying, you know, it's a challenge right now because of the
regulatory system as well. We don't have a way to approve a
drug to extend healthy aging. And so proof of principle and
advancing some of these inexpensive therapeutics that everyone
can access, it would be fabulous to have Federal support for
that.
Chairman Foster. Thank you. And I guess I will just yield
to the Ranking Member at this point.
Mr. Obernolte. Thank you, Mr. Chairman.
Dr. Horvath, I wanted to ask about a part of your testimony
you were discussing that there will be a need for a new
regulatory framework for the treatment of healthy people, as
opposed to our current regulatory framework that's geared more
toward treating people who are ill. I wondered if you could--
that's very much our bailiwick, and it's something that's going
to be useful for us to start thinking about. Can you talk about
what a framework like that would look like and how it would
differ from the existing framework that we have?
Dr. Horvath. I think it would be important to develop
different metrics of measuring success. And the reason is,
imagine you have a drug that you give to a middle-aged person,
a 40-year-old, with the hope that it will prevent many future
diseases. But then you, of course, would have to follow this
person for decades. And it's cost prohibitive. So in order to
advance medications that prevent the onset of these age-related
diseases, we need to find surrogate metrics, as opposed to
actual disease states, in other words, biomarkers. And it would
be very good if a regulatory agency could take the lead, to
organize a panel and really carefully look at the data,
generate additional data, and develop surrogate markers, what
we call surrogate endpoints that are trustworthy, that most
scientists believe in. But then also these should be available
then to the biotech industry so that it unleashes investment
from private sources to fund these trials.
Mr. Obernolte. Right. Actually, Dr. Niedernhofer, let me
ask you about that as well because in your testimony you were
talking about one of the barriers to the advancement of
geroscience being the lack of aging biomarkers, and it seemed
like if we had--I think that's exactly what Dr. Horvath is
discussing, you know, that we would need these aging biomarkers
to be able to prove the therapeutic benefit that would need to
fit into the regulatory framework of healthcare. So could you
talk about what those biomarkers might look like and how we
can--how we can eliminate that barrier?
Dr. Niedernhofer. Yes. And I have deep respect for the
biomarkers--the epigenetic biomarkers that Dr. Horvath has
developed. I think they are some of the key tools in our
toolbox, but we need more. And I think it even stems from
trying to assess what people value in old age across very
different ethnic and social economic groups, just understanding
what they value, what their goals are, starting there, so there
could be functional tests that we have, how quickly you walk,
how quickly you get up and down out of a chair, what's the slow
decay in your ability to do a lap around the track. It should
also incorporate molecular markers that are very quantitative,
and we have a lot to learn here. But I think it should start
really with a conversation between regulators, what they need
to prove safety, efficacy, and then the scientists who can
actually figure out how to measure those and develop those
tools.
So I agree with Dr. Horvath that it'd be lovely to have
panel discussions where we really anticipate what's going to be
needed to compress the length, the duration, and the size of
these clinical trials so that we can afford them and do it in
an iterative process, maybe even in parallel, so that we're
able to test many different approaches and really come up with
an answer to extend healthy healthspan as quickly as we can.
Mr. Obernolte. Just playing devil's advocate, though, I
mean, I think we're talking about something more than just
measuring a deterioration that occurs with aging. And I mean,
for example, I'm feeling very old this morning because I had
congressional football practice, and my body's reminding me
that--that it's not the same body that it was 30 years ago when
I actually played football. But, I mean, you could measure my
time running around a track, and it certainly has decayed in
the last few years. But the whole purpose of a therapeutic
treatment is so that that will not decay, right? So you
wouldn't have that marker, right? So we need something cellular
that provides, you know, a marker for the efficacy of the
treatments that we're proposing to be able to--you know, to fit
into the regulatory framework we have. I mean, don't we?
Dr. Niedernhofer. We absolutely do, but I do believe as
well that you need to tie it to some functional outcome so that
you really--the individual is experiencing the benefit as well.
Dr. Horvath. I could add a few comments. Aging really
starts very early on. On a molecular level, children already
age in some shape or form. And so it is correct, we do we need
these early molecular biomarkers as well.
I want to add another point, which is when you put two
scientists in the room, you will get two different opinions.
They will never agree on which biomarkers should be used. So
there's really a need for leadership, regulatory leadership,
and impartial leaders making decisions, executive decisions,
informed decisions, decisions based on data, rigorous testing,
but leadership would help the field tremendously.
Mr. Obernolte. All right. Well, thank you very much. I
yield back, Mr. Chairman.
Chairman Foster. Thank you. And we'll turn it over to
Representative Perlmutter.
Mr. Perlmutter. Dr. Olshansky, I've got a couple of
questions for you. So this morning, I was going through my news
feeds, and one of the articles that pops up is ``90 will be the
new 40 in 10 years,'' you know, which, again, is I'm, you know,
at 69 sort of marching--time keeps marching on. That's--that
was music to my ears in looking at that. But there are--one, is
that--do you think that's a legitimate headline? And to the
other panelists, you can answer that, too. But my second
question would be more, again, going back to the macroeconomics
of this, you know, to Social Security and things like that. If
in fact we are moving forward where people can live longer,
healthier, more productive lives, then there are some things on
a macroeconomic level that we need to prepare for, one of those
being Social Security. So I'll just let you respond generally
to both of those questions.
Dr. Olshansky. Yes, so I'll respond to the second one
first. So look, when geroprotectors come online, they will
indeed successfully produce more healthy older people. There
will be more people surviving past the age of 65, 85, 90 than
any time in history, in part as a result of these therapeutics,
so Social Security will be challenged. There's no question that
the Social Security Administration is going have to deal with a
larger population that will be drawing benefits for a longer
time period.
However, if we're extending healthy life and people decide
to work longer and it will be their option, you will now have
justification for delaying age at entitlement, whether we're
pushing back 62 and 67, by how much, there would certainly be
logical justification for altering age at retirement, and that
would certainly deal with the issue associated with more
healthy, older individuals drawing from Social Security.
I saw the same story you saw, by the way, on ``90 is the
new 40 in 10 years.'' It's the 10 years, by the way, that
bothers me. The 10-year claim has been made for 2,000 years,
you know, that some magical breakthrough is going to happen in
exactly 10 years. So the 90/40 might be a bit of an
exaggeration, but the concept, I think, is right on target. And
that is, it will take a longer time period to grow old
biologically. Maybe, you know, it'll take 90 years to become 70
or 80 years to become 60 or something along those lines, but
practically, at our level, the way in which you and I and all
the listeners operate, we will experience biological time at a
slower rate. A year from now you will not be a year older. You
might be nine months old, or eight months older. It's not going
to stop aging; it's going to slow it down. And in the end,
that's what we want is to retain our youthful vigor for a
longer time period.
So some of the numbers--I don't like this embellishment and
exaggeration that I see in the field all the time. But the
overall premise, I think, may be on target.
Mr. Perlmutter. Well, I'm smiling because we have this
thing at the YMCA called the e-gym, where it sort of tracks you
and all this stuff, and it has biological age. This makes me
very happy when I look at it. It says my legs are 36 years old,
my core is 35, and my chest and arms are 27. So to any future
employers, I give them this, say, look, there's a lot of years
left in this guy.
So, you know--but I think what you're all talking about is
that there are potential scientific breakthroughs, whether it's
through the use of biomarkers to kind of manage things or
metformin or whatever the drug was that was mentioned. But
there are also other things that we're becoming, you know,
smarter about in terms of nutrition and exercise and those
kinds of things, which, again, Dr. Niedernhofer, you know,
we're trying to both have quantitative objective kinds of
markers but also there's a qualitative element to this is, you
know, does it hurt every time you get up out of a chair? So I
don't know if you have any comments either to my biological
age, which I think is pretty good, or otherwise?
Dr. Niedernhofer. Well, I would say congratulations. And we
need to continue to build these tools so that we can do this
for everyone and accurately. I don't completely trust the tools
that we have entirely at this point, but obviously----
Mr. Perlmutter. Well, I do.
Dr. Niedernhofer [continuing]. You're good. You're on a
great trajectory.
The other thing I would just comment about sort of in terms
of the economy is just picture a person who's in memory care
versus a person who's independent, which I think is what
geroscience approaches can achieve, a little, you know--an
extended period of independence and activity. So they are going
to contribute one way or another to the economy much more so
than somebody who's sadly trapped in memory care.
Mr. Perlmutter. Thank you. I yield back to the Chair.
Chairman Foster. Thank you. And it's--I believe we can
actually have another quick round of questions because this
remains fascinating. So--and I will now recognize myself for
five minutes.
What is the current understanding about the evolutionary
advantages for senescence? Because that has me really confused.
You know, apparently, some species like lobsters do not have
senescence and then others do. What is believed to be the
advantage of why this is as evolved?
Dr. Niedernhofer. I believe this is a question for me?
Chairman Foster. Go for it.
Dr. Niedernhofer. Thank you. So senescence evolved as a
tumor-suppressor mechanism. In my mind, it is one of the most
potent anticancer programs we have in our body, so it's
necessary for multicellular organisms that live a very long
time. So if a cell is stressed, in particular, the DNA of that
cell is stressed, if that cell will respond by activating
signals that say I will never copy myself again and make a new
cell, and that prevents that damaged stress cell from turning
into a tumor. So it's very advantageous.
We also know that there's senescent cells in a number of
physiologic, healthy contexts. So during wound healing,
obviously, there's a stress to your skin if you're cut open,
and senescent cells will accumulate at that site to help heal
it. But these are very acute events that are cleaned up and
help you carry on without having the chronic inflammation that
can come with building up senescent cells with aging.
We think part of the problem with senescence in old age is
that senescent cells just accumulate because your immune
system, the function of it declines a bit with aging, and
therefore, you're unable to receive signals from the senescent
cells that call in your immune system to clear them. So it's a
lovely cancer-protection mechanism, contributes a lot to
various physiologic states in mammals, but turns against us as
we get older, as many things do in biology of aging.
Chairman Foster. So do you see the mechanism throttled down
in, you know, elephants versus mice? Or is it a pretty
universal pattern there?
Dr. Niedernhofer. So that's a great question. So we've
learned a lot from comparing different species. And indeed,
elephants are some of the longer-lived species. They have extra
copies of genes that reduce their cancer risk, and therefore,
they just experience much less cellular senescence. But there's
still a lot to learn in this space. And I think we're a little
bit caught up in just lack of definition of a true senescent
cell. It's very hard in my mind to talk about healthy senescent
cells and pathologic senescent cells and not get everybody
confused.
Chairman Foster. Yes. Was there someone else who wanted to
comment?
Dr. Olshansky. Yes. Yes, if that's OK. So really good
questions, by the way. So this issue of humans and elephants
and dogs and how long we live and why it's all relevant is
actually central to the study of aging and longevity. But keep
in mind, we cannot have aging or death programs that evolved
within us. We don't have a ticking time bomb that goes off at a
certain time period. Natural selection could not have led to
the evolution of ticking time bombs in our body. So think of
aging and senescence as an inadvertent byproduct of fixed
genetic programs that exist for growth, development, and
reproduction. And that explains why different species live
different lifespans. You know, dogs live, you know, about 15
years, and they go through puberty at nine months. They go--you
know, their reproductive window is much shorter. Our
reproductive window is longer. We live longer as a result. So
there's this calibration between duration of life and the
reproductive window of the species.
But importantly, there isn't a death program. And the
absence of a death program is the reason why we can intervene.
It's the reason why these geroscience interventions are going
to work, and it's also the reason why diet and exercise can
actually have an influence on how healthy we are and how long
we live as well. The field is wide open for intervention.
Chairman Foster. Now, are there examples of where the
extension of the healthspan is not associated with the
extension of lifespan in any animal studies or so on? Are
these--you know, it's a very--you know, politically, it solves
a lot of problems if the main result of these--all these
treatments is that you're healthy longer, and then you die at
pretty much the same time? If it is--if that's not really the
case, then it's a much more complicated set of policy
implications. So what's the best understanding of that
relationship?
Dr. Olshansky. I can comment real quickly. I think that
when we introduce these geroprotectors, we know that we will
see a compression of morbidity and disability. By how much
exactly, I think we cannot yet determine. We will need the
biomarkers to make that determination. The unanswered question,
which I think is the one that you're addressing, is how much
longer might we live as a result? And we don't know yet how
much longer we will live as a result. And keep in mind, when
scientists and others come along and suggest we're going to
live 10, 20, 30, 40, 50 years longer as a result, there's no
evidence to support that at all. We cannot--that is an
untestable hypothesis on any sort of radical life extension
proposal that folks are making. So that's one of the reasons
why we're focusing in on healthspan. It's something we can
measure and we can detect very quickly in these types of
studies.
Chairman Foster. So I guess I was asking about animals. Any
any hints from smaller animals? Dr. Horvath?
Dr. Horvath. Yes, you know, I've looked very carefully at
epigenetic determinants of what I call maximum lifespan in
species. We have analyzed 348 mammalian species, from the
maximum lifespan two years in a shrew to the bowhead whale,
whose maximum lifespan is 211. And there is a strong epigenetic
signal. But the interesting finding was that whatever
determines maximum lifespan was actually quite different from
what relates to human mortality risk. So my opinion is that the
determinants of maximum lifespan are quite different from what
we care about here, which is healthspan.
Chairman Foster. All right. Thank you. And I'll yield to
the Ranking Member.
Mr. Obernolte. Thank you, Mr. Chairman.
Dr. Niedernhofer, we were talking a few minutes ago about
the barriers to the advancement of geroscience that you had
brought up in your testimony. And one of the barriers that you
mentioned is lack of public knowledge. Can you talk a little
bit about why that's a barrier and what we can be doing about
that?
Dr. Niedernhofer. Yes, thank you for asking. I just feel
that it's a little bit of a rarefied crowd that really
understands geroscience at this point. And I feel like we need
to gather a lot more information from various stakeholders in
the United States to understand what they value in old age and
how we can address their needs as well. This may not be for
everyone. I think deeply about Native Americans who can't wait
to get old and be an elder in their community, and they don't
want to interfere with that process. So I think we need to
gather information and educate people to get buy-in because I
think there's an awful lot of these people who would be
tremendously excited about it, but we need to understand across
our population who--you know, what the various opinions are
about this approach.
Mr. Obernolte. Well, I mean, I think, also, maybe caution
is warranted because, as Dr. Olshansky just pointed out, we
don't have any scientific evidence that we can extend lifespan.
We just know that we have these cellular epigenetic clocks
that, you know, we think we can--we think we can eliminate. And
we also think that maybe we can reverse some of the effects of
aging such as Alzheimer's disease, which, you know, would
have--by itself would have a huge--a huge benefit for society.
But, you know, we really can't promise people anything. And I
actually think that if we're--when people hear about this, they
could be tremendously excited. It's just that, you know, we
have to be very cautious about being realistic with them about
what we can and can't promise.
So, anyway, I thought that was interesting. But that
would--I mean, to your point, that would help eliminate some of
the other barriers that you brought up, you know, certainly,
lack of scientists, if we evangelized, you know, this emerging
field better, we could get more young people in training and
fields to be able to do this kind of research. Lack of funding,
certainly, you know, a greater public awareness would help us
with that.
Dr. Horvath, we--the Chairman was having what I thought was
a really interesting discussion about--about clinical trials
and how they're funded, given that many of the drugs that we
are investigating in--for the use of geroscience are off
patent, and that eliminates a profit incentive for private
industry to fund those. So, you know, we're funding research
through NIH, we're funding research through NSF. Do you think
that this is a barrier to actually bringing therapeutics to
market? And if it is, then how much more funding do you think
we would have to do?
Dr. Horvath. Yes, just to echo what you said, it would be
wonderful if we found incentives to repurpose existing drugs or
drugs that are off patent, natural products. Now, I'm thinking
about how to do it, you know. I really don't have a good
solution, unfortunately. But yes. So many scientists really
work on that. I want to say most scientists in the geroscience
field actually work on that. Why? Because natural products are
safe. And also to remind everyone, when you go back to a dinner
party and talk about aging, everybody will share their favorite
supplements with you. What are they taking? Vitamin D,
whatever. And what is so frustrating to me personally is
everybody has their favorite one, but the evidence is so weak.
And it would be wonderful then if we found ways to do rigorous
studies of these supplements that so many of us are taking. And
yes, I'm not sure whether I answered your question.
Mr. Obernolte. Well, you know, it's--it might be a problem
that solves itself because once the--we can state credibly that
there are health benefits to doing this, there's going to be
incredible public interest and public demand for this. And so
that's going to create a market void for companies to fill.
And, you know, that'll be a source of private funding, so we'll
see.
Well, it's been a fascinating discussion. In closing,
though, I want to comment on Congressman Perlmutter's
biological age and just point out how much we've enjoyed having
him here on the Committee. And since the biological age is so
low, you definitely should not be, sir, retiring from Congress.
I yield back, Mr. Chairman.
Chairman Foster. Yes, we'll be using the Yamanaka factors
to clone Perlmutter. So it's all underway. OK. Representative
Perlmutter.
Mr. Perlmutter. All right. I thank the gentleman.
You have used, all of you, a euphemism of compression of
morbidity, which I'm not--as a lawyer, I'm going, OK, what the
heck does that mean? Does that mean when you die it happens
quick or--I mean, Dr. Olshansky, I think you've used it the
most. So tell me what it is you mean by compression of
morbidity and why that's an important concept.
Dr. Olshansky. Yes, great question. So it basically means
everything that goes wrong with our bodies and our mind with
the passage of time would be delayed. If normally you would see
an expression of a particular disease or a disorder at age 60
or 70 or 80, it might be delayed to 70, 80, or 90. And when
things go wrong, they would happen more rapidly.
And so it's--actually, it's a fairly straightforward
concept, and it's not foreign to us because we already see it
among subgroups of the population that exist today. It's about
15 percent of the U.S. population called super agers. And these
are individuals that make it out past the age of 80 cognitively
intact. You can't really tell the difference between them and a
40- or 50-year-old. And so we see it today among subgroups of
the population that are already experiencing morbidity and
disability compression. They're healthy, they're active,
they're exercising, they can be president, they can be CEO
(Chief Executive Officer), they can do whatever they want. And
it's 60, 70, 80, 90. And it's already here today among
subgroups.
So it's what we want. It's a healthier life for a longer
time period. And basically, age becomes just a number. It
becomes largely irrelevant. And when things go wrong, they go
wrong quickly. And so it's not going to stop us from aging.
It's not going to stop us from dying at some point. But it will
lead to a longer period of youthful vigor. And in the end,
certainly, that's what my father told me when he was in his
90's. He said all he wants is his health. And I couldn't agree
with him more. It is the most precious commodity, and that's
what this is all about is extending the amount of this precious
commodity that all of us have in life.
Mr. Perlmutter. Well, I want to thank you. I want to thank
your fellow panelists. This has been fascinating. I think
that's a good place to close. I'll yield back to the Chair.
Chairman Foster. Thank you. And now, before we bring this
hearing to a close, I want to just thank our witnesses again
for testifying before the Committee. The record will remain
open for two weeks for additional statements from the Members
and for any additional questions the Committee may ask of the
witnesses.
And the witnesses are now excused, and the hearing is now
adjourned.
[Whereupon, at 11:18 a.m., the Subcommittee was adjourned.]
Appendix I
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Answers to Post-Hearing Questions
Answers to Post-Hearing Questions
Responses by Dr. Jay Olshansky
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Responses by Dr. Laura Niedernhofer
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Responses by Dr. Steve Horvath
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Appendix II
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Additional Material for the Record
Letter submitted by Representative Bill Foster
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