[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:]
    
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    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:]
    
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    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:]

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    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

                              ----------                              


                   Additional Material for the Record




             Letter submitted by Representative Bill Foster
             
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