The Art of Aging Well

Hello, welcome! I’d like to start our program. We still have people
who are signing in, but because we do have
a livestream audience, I’d like to start
relatively on time. I’m Gina Vild, I’m the Associate
Dean for Communications at Harvard Medical School. And I am so thrilled
to be here today. This is my 10th year
introducing along with seminars, and this is our 18th
Longwood Seminar. And this, of course, is
our inaugural seminar. We are so thrilled. This forum was
developed 18 years ago to try to share the knowledge of
Harvard Medical School faculty with our neighbors and
our neighboring community. It has since grown
exponentially and we now livestream it around the world. So I’d like to thank all
of you for being here tonight, and thank you for your
engagement on our social media channels and for taking
time to attend in person. This is really a
treasure of an event and for Harvard
Medical School and you are part of that treasure
by being a repeat audience. So I’d like to ask now, for
whom is this your first Longwood Seminar? Oh great, excellent. OK, and how many of you–
quick show of hands– have been here before? Good, good, good. Thank you. There are so many familiar
faces here, and as they said, it’s my 10th year and it’s
really wonderful to welcome you back here again tonight. We were wondering if maybe the
snow would keep people away, but I know this topic is of
particular interest and snow did not deter anyone tonight. I also would like to
say to those of you who are watching through
livestreaming through our Facebook channel
and YouTube, welcome. Typically, if this event
is typical of past years, we will have people from
36 countries watching and the audience numbers
in the tens of thousands, so you’re an important part of
our Longwood Seminar community as well, so thank
you for joining us. We select the topics for
the Longwood Seminars based on the preferences
of our alumni. So we offer 10 topics and
there were four topics chosen for this year. This evening’s topic,
The Art of Aging Well. March 28th we are offering The
Science of Pain Management. April 24th, Bridging
East and West– New Frontiers in Medicine. And May 9th, our
final seminar will be Weighing the Facts of Obesity. So as you can see, we choose
our topics based on your input. So we’ll be sending you surveys
within the next few weeks and we encourage you to give
us honest feedback– what did you like, what did you not
like, what recommendations do you have for the future that
will make these seminars even more meaningful for you? Tonight’s topic is one
that is one of our– had greatest preference
of all the seminars that we have offered
in years past, so we’re thrilled to
be able to offer it to you with this particular
panel of experts. And because we know this
topic is of interest, I want to share with you
some additional resources on the topic. I invite you to take a look at
the Harvard Health publishing website, and that web address
is If you forget, you can type
in Harvard Health publishing. There you’ll find many
additional resources– special health reports,
newsletters, e-learning, and blogs on how to age well. We also recently launched a
program called Living Better, Living Longer. We offer a wealth of resources
on that topic as well. The website is And tonight, if you are
interested in finding out more about Harvard Health
Publishing, Cathy Finn– would you raise your hand? She’s over here. She works with Harvard
Health Publications and is available
after the seminar to answer any questions
that you have, and she also has
literature on the table outside near the sign-in. On the screen, you will
now see information on how to obtain
certificates of completion as well as professional
development points for teachers. And teachers have long been part
of our core Longwood Seminars audience and we’re
just thrilled to have you be here again
tonight and this year. We also invite you to
view the Longwood Seminars website at our HMS
website, and there you’ll find content on
many of the seminars from past years, the topics
of which for the most part are EVERGREEN. So that’s an opportunity to
really broaden your experience with the Longwood Seminars. Our speakers will
be taking questions at the end of the presentations,
and you can write yours down on the index card
that was given to you when you signed in, so keep
that and members of our staff will be moving
through the aisles and you can hand them
the questions we’ll get them to the moderators. Don’t worry if you’re not
in the auditorium tonight. If you’re watching us
through livestream, please put your questions
in the Facebook and YouTube comments section
with the livestream, or you can tweet them
to us at #HMSMiniMed. And we do invite you to be part
of our Twitter conversation throughout the evening. So now for this
evening’s seminar. Something we all need to know
about the art of aging well. The actor George Burns,
who lived to be 100, humorously once said, you
can’t help getting older, but you don’t have to get old. So was he right? Our experts will tell you. Tonight, the good
news is that people are living longer and enjoying
a higher quality of life than a generation ago. We have a better
understanding of how diet, exercise, a positive
attitude, and staying socially connected can help us age well. But what does aging even mean? Why do people age differently? And why do some people we
know tend to defy the aging process altogether? And what are the
latest discoveries that can help keep us healthy
well into our later years? Many Harvard
scientists are working to answer those very questions. We’re fortunate to have some
of our most senior experts here with us tonight. They will share
their research that may help us live
longer, healthier lives. I’m delighted to introduce
to our panel of experts. Dr. Alexandra Touroutoglou
is an Instructor of Neurology at Harvard
Medical School and an Assistant to Neuroscience at
Massachusetts General Hospital. Dr. Lewis Lipsitz is a professor
at Harvard Medical School, the Director of the Institute
for Aging Research at Hebrew SeniorLife, and Chief of
the Division of Gerontology at Beth Israel Deaconess
Medical Center. And I believe this is a
repeat command performance that he spoke to the Longwood
Seminars a few years ago. And first, you’ll hear
from Dr. David Sinclair. Dr. Sinclair is a Professor
of Genetics and Co-Director of the Paul F. Glenn
Center for the Biological Mechanisms of Aging at
Harvard Medical School. He will share some of his
exciting new discoveries about aging. So again, thank you
so much for being with us for our 18th year,
and please give a warm welcome to Dr. Sinclair. [APPLAUSE] Thank you, Gina. Thank you, everybody for
braving the snow here in Boston, and welcome, everybody online
to this Longwood Seminar series. We have three great
talks to that tonight. Well hopefully, at least
two, we’ll see how mine goes. So I’m here to
start the night off to give you some good
and some bad news, OK? The bad news is that
we’re all born– pretty much all born
in the 20th century. And that means that
we may not live to see some of
the amazing things I’m going to talk to
you about tonight, but the good news is that
scientific progress is going extremely quickly
and it may actually be that we were extremely
fortunate to catch just the beginning of the
equivalent of human flight, but for aging. And I was just sitting here
with Professor Lipsitz talking about how privileged we
are to work in this age where miracles seem to happen. And so in my first slide, I
posed this question to you– what will be the largest global
change over the next 30 years? And if you open any magazine
or the daily newspapers as we used to call
them, your iPad, you will see that there’s a
lot of excitement in the tech world, mainly, about how our
world will be revolutionized. One day pretty soon, we’ll be
able to just talk in any room and have the lights come on– we actually can do that
already, what am I saying? The future is already here. But my point to you tonight
is that in 30 years, these devices will seem
like a blip in history compared to what is going
to happen to our biology and to changes in
medicine, because I’m very fortunate as the two
speakers are tonight to have a front row seat
of what is coming, and I’m really excited to
be able to share with you some of that view here tonight. Most members of the
public have no idea how close we are to some really
astounding medicines coming down the line, and I really– I get up everyday
out of bed thinking, I just can’t wait to
see what comes next. OK, so here’s a young boy. He happens to look
a bit like me. According to this
genetic test that he did, he is related to me. Thank goodness. [LAUGHTER] Or my wife would
have been in a lot of trouble. So Benjamin here is a new breed
of child in the developed world and increasingly
across the planet that will be able to live in a world
that we can barely imagine, and I hope after tonight,
you will be able to imagine. So Benjamin here is taking a
genetic test just by spitting into a tube, and he
gets back a report that tells him where
his ancestors came from, how much of the right
arm of chromosome he got from his grandparents
and great-grandparents. And we’ve actually
genotyped our entire family, so we can use this not
just as an educational tool for our kids, but
to teach them how they’re going to be able to get
through this coming century. And I don’t say that lightly. Benjamin was born
now 10 years ago, but there’s absolutely
no doubt that he’s going to see the 22nd century
unless he’s very unlucky. Most kids who are
born today will be able to be healthy into the
90s and even into their 100s, and that’s if we don’t
have a breakthrough. The kind of breakthrough that
I’m talking about tonight could have us living even
further in a healthy way, and that’s the main point. So this is a snapshot of many of
my family members in 2005, OK? So we’re now going
back 13 years. And just to orient you,
we have my grandfather on the right, my grandmother
in the middle at 80, my mother who at the time was
62, and my father who was 65. And this is my wife down
at the bottom right. I show that because out
of all of the people who have numbers above their
heads, only one of them is still alive. The other three lived
fairly horrific moments for the last few
years of their life. Now we’re talking
about brain aging. Now brain aging is one of the
most traumatic of any process to happen to humanity. If anybody here– and I’m sure
many of you have had family members who’ve experienced
some dementias, Alzheimer’s is
just one of those– you know how horrible it is
for not just the individual, but particularly on the
families themselves. And people can spend a
decade in this state. In fact, I put it
to you that actually half of the population, the
adult population of the United States has at least
one chronic disease, and that is what we spend
86% of our health care on. So what if you
could greatly reduce the amount of chronic disease? And instead of just keeping one
organ or tissue healthy, which is what we do when
we go to the doctor and get a statin for
your heart and pill for your blood
pressure, that’s great, but what about the
rest of your body? And throughout the 20th
century and to this day, most researchers and clinical
trials here in Boston and throughout the
world are focused on treating one
disease, but we now have the knowledge and clinical
trials in progress where one medicine can
treat potentially 20 different diseases,
and as a side effect, you’ll live longer
and healthier. So we’ll get to who’s
still alive in a minute. Now often I’m asked, Dr.
Sinclair, Professor Sinclair, aren’t you worried
that you’re dooming us all to overpopulation
and who wants to be old anyway for longer? And what I’m trying to
show on this slide here, hopefully it’s clear is
that if we’re successful, at a minimum, what
we’re going to have is that the last decade or
so of life or even longer is going to be just as
healthy as you felt when you were in your 20s and 30s. And I know it’s possible. There are many of us who
are genetically and soon pharmacologically will
do this, and we’ll hear Professor Touroutoglou
talk about that. So hopefully I’ve convinced
you this is a valid pursuit. I think I’m preaching
to the choir here, but often people
forget that we’re not keeping people older
for longer, we’re talking about keeping
people younger for longer. So that you don’t have to
worry about getting cancer in your 60s or heart
disease and have a stroke in your 70s and 80s. And we can do this
very easily in the lab. I have mice that are around
this vicinity– well, my lab is upstairs– that we can keep mice
alive for a lot longer and they die fairly quickly
and painlessly as far as we can tell, and this
is what the future offers. And when this happens,
we’ll look back at today and we’ll say, wow, I would
never go back to those days. The same way we look back at the
early part of the last century where people would die
from an infected splinter. So how is this
possible, you may ask. What’s been the
big breakthrough? And the biggest breakthrough
has been the realization that our bodies are not just
simple cars that wear out, that’s the old view of aging. And of course, by
this analogy, there’s no way anyone could develop a
drug that could fix everything, because all different
things break down. It would be as if we throw a
wrench at this car on the right and it made everything work
again– that’s impossible. But our bodies are much
more complicated than a car. It’s the equivalent
as if we found the body shop repair people. Our bodies are capable
of immense repair. They just lose their
memory on how to do that. They become less and less
able to repair themselves. If you take my son, for
example, he gets cut, he gets an infection, he
will heal very quickly. Why is it that as we get
older, that declines? And eventually it
becomes so bad that you can die from an infection
when you’re old? We believe as a field– not just my lab, but a
whole group of hundreds of labs around the world– that we finally understand
how it is that the body when it’s young can fight disease
but cannot when we’re older. Not only that, not
just disease, but how do we feel– why do we
have more energy when we’re young than when we’re older? Why do we groan when we
get up out of a chair or out of bed as we get older? We take it for granted. It’s almost so common that we
don’t even ask the question, why does this happen? So the good news
is that there are sets of genes that researchers
throughout the world have discovered that
control our bodies’ health. Now there are some ways
to make them more active. Now we know that exercise
and being lean and dieting, eating a good diet
are good for you. Even eating a Mediterranean
diet and eating these molecules from stressed-out
plants is good for you. Why is that? And I don’t believe that
it has anything to do– or not very much to do, I should
say, with antioxident activity. What’s going on is that you’re
activating the genes that repair the body and tell the
body to be in a fitter state and try to survive during
these times of adversity when we’re running
and we’re hungry. Some of those genes
are called the sirtuin. There are seven of
them in your bodies. Everybody has them. Without them, you’d
be in real trouble. But we can engineer mice to
have more of these genes, and in many cases,
the mice are healthy. And in a couple of cases,
a couple of the genes, the mice lived longer,
and they lived longer because they didn’t get
the diseases of old age. Now we can’t genetically
engineer ourselves, at least not yet. There are certainly some
people here at Harvard who are working on
some genetic therapies to help people have a
better genetic repertoire, particularly to repair what’s
lost over time in terms of genetic disease. But let’s just say within our
lifetimes, most likely what’s going to be beneficial
to us are drugs that are developed through
the traditional route. And what’s exciting is that
we now know how to do this. It is no longer surprising
to anybody in my field that within the next
five years, somebody is going to make a
drug that doesn’t just treat heart disease, but
treats almost every disease that we get when we get older. And I’m not the only
one doing this anymore. I used to be one
of the few people– there’s almost
every month there’s a new big discovery
and/or a new company that started to make this come true. So in my research,
what we’re looking for is a molecule that activates
these sirtuin pathways that I just mentioned, the
genes that we believe make you fitter when you
exercise and when you diet. Now this is quite a
remarkable molecule. This is called NMN. Don’t confuse it with M&M’s. [LAUGHTER] M&M’s are not as good for you. NMN is what the body uses to
make a molecule called NAD. Now NAD turns out to be
a remarkable molecule. It’s very small,
it’s just a chemical. It’s related to vitamin B3. And what we used to think in– when I was back in
high school, was that NAD was just important to
keep chemical reactions going in the body. All it did was housekeeping, not
that housekeeping is a bad job, it’s just that it’s not
particularly exciting. What was discovered
about 20 years ago is that NAD also controls the
body’s defenses against disease by activating those sirtuin
enzymes that I told you about. So now what we can do is
we can feed cells and even animals and even people in
clinical trials molecules like NMN and get their NAD
levels up, boost their NAD– these are called NAD boosters. And what we see is really
quite remarkable in the animal studies. And very soon, we’ll know if
this works in people as well. Now you might ask, Dave,
why you boosting NAD if we already have a lot of it? Well first of all, NAD
is extremely important. Without it, you’re dead in about
30 seconds, so you want NAD. But do we have enough? Well, we definitely have enough,
I think, when we’re in our 20s. My son has enough. If you took his blood
and measured it, he’d have abundant
amounts of NAD. The problem is, that by the age
of 50, you have half the levels that you had when you were 20. And as a result, your chemical
reactions aren’t just slower, more importantly, your body
doesn’t fight against diseases anymore the way it used to. So when we give
old mice this NMN, what we do is we just put
it in the water supply and they drink it for a
few weeks, and then we ask, what happens to those old mice? Let me show you what
happens to these mice. Now I admit that these are
black mice on a black treadmill, but hopefully you can focus
on their tails and their ears. Now one of these mice has been
drinking NMN for a few weeks and one of them has not. And this is fairly
a typical result. We are about to tell the
world in a publication that we are able
to greatly increase the endurance of old mice
back to the levels when they were young again. And the way this
works is it actually builds new blood
vessels in the muscle– and we think in
the brain as well– to be able to get rid of
toxins in the body up as they build up during exercise
and during aging. So this is great. What this means is if this could
be done for humans, for us, we could take a
pill every morning and get the benefits of
exercise without having to necessarily exercise. OK? It sounds too good to be true. And I agree, it does
sound too good to be true, except so far, it is true. This is cutting-edge science,
this is in the world’s best scientific journals,
so hopefully it will translate to people. You might ask, is
this an excuse just to sit around and pop
a pill and eat chips? The answer is no, it’s not an
excuse, because if you’re fit and you take this molecule, if
you run while you’re drinking this molecule or you drink
it and then you go for a run, these mice now can run more
than twice as far than they did. We are developing
super mice here. Now we just had the
Olympics, I’m not sure what’s going to happen
at the next Olympics if this turns out
to be true, but what it means is that we’re finally
potentially able to reach the best that our
bodies can give, not just when we’re young,
but even into our older age, so that we don’t groan when we
get out of bed in the morning. And in fact, if we start
to lose our mobility and we’re stuck in a
wheelchair or bedridden, it’s those people
that would absolutely need exercise in a pill– for those people. And imagine if they could start
walking again or exercising again and get the
benefits of that, that would be a beautiful
positive cycle that doesn’t just allow them
to exercise, but to get the rest of their body up
and active and their brain– more blood flow as well,
which we’ll hear later, I’m sure, about the
importance of that. So this molecule, others as well
have worked on it for years. For the last five
years, we’ve seen that NMN and a
molecule related to it called NR, when
given to old animals, protects them against a
whole variety of diseases– diabetes, memory loss,
hearing loss, eye sight loss, inflammation, it even
improves wound healing. This is, as far as I
can tell, the closest thing to a reversal of aging. So we’ll see how far we can go
and whether this will actually turn out to be true in people. The good news is is that so
far, a very safe molecule or group of molecules. I mentioned that it’s
basically a super vitamin. The other good news
is that this is a naturally-occurring
molecule, we all have NMN in our bodies and
NAD, we just lose it over time, and all we’re talking about
is replenishing those levels. So there’s a
clinical trial that’s ongoing here at
Harvard Medical School and at the Brigham
and Women’s Hospital, and it’s a very exciting
time for my colleagues and I to see whether
we can translate the last 20 or so years of
amazing discoveries in animals finally through to people. Now I’m under no illusions
that this is going to be easy or that it’s going to be quick. Most clinical trials are
in the hundreds of millions of dollars, and they also
cost, in terms of time, it’s at least five years. But how long has humanity
waited for something like this? And how big is the payoff? It’s in the trillions of
dollars in the economy. That’s money that
can be put back into other things such as
education and the environment. And we will not have a
greater GDP, we’ll actually– or loss of money in
the economy, we’ll actually have a lot
more money to spend if we’re able to keep
people healthier for longer towards the end of their life. And I’m not an
economist, but all economists that
study this say, this is the best bang for the buck
in terms of the health care system, and if we
don’t do something, we’re in trouble anyway. So let me just finish
now by highlighting the member of our family
that has survived. My father is now 78. He’s in Sydney,
Australia, where he landed after escaping Hungary
in 1956 with my grandmother. Now out of all the people
that I’ve mentioned here in my family who had
numbers above their head, my father was very
interested in our research and started taking some
of the natural molecules that we were discovering
about a decade ago. Now for those of you who
say, Dr. Sinclair, you know, a science experiment
needs more than one person, I’m absolutely aware of that. I’m not going to publish
this result any time soon. But it is interesting. He’s certainly not dead yet. In fact, he’s gone
from a person who was not looking forward to the
next 10 years of his life– he had retired, he
was slowing down, he didn’t expect to live a lot
longer than another 10 or 15 years. So what’s happened to him? This is what he did last year. That should say 2017. So the top left is he’s
climbing trees in Germany and putting on skis
up on the ziplining. Top right is he’s going
up to the tallest mountain in Tasmania in Australia. The lady on the left
with the red t-shirt is my ex-girlfriend. Go figure. I have nothing– I have no problem with that. It’s my wife who
feels it’s strange. [LAUGHTER] He’s climbing in Montana. He was doing abseiling or
rappelling down a mountain. He’s gone caving, he’s
riding these bikes, he went whitewater rafting. And just about everywhere
he goes, people say, we haven’t had somebody
your age do this before. So again, it’s just
one anecdote, but what I would like to make the
point, if nothing else, is that this is the
way the future will be. This is what we’re aiming for. The people in their
70s, 80s, and beyond will be able to have
a life that isn’t just pain and sorrow for
them and their families. And you know what? My father started a new career. He was so optimistic
about the future, he started working
for a nonprofit at the University of Sydney,
he now actually oversees clinical trials. But at his age, when I first
showed you him, if I had said, you’re going to
start a new career when you’re 77, he would have
said, tell me another one. So he’s got a new
lease on life, I’m really looking forward
to seeing how he does over the next decade or so– and so is he, by the way. So finally, I just
want to finish up by giving you a little insight
into how far some of this can happen. Again, I did an experiment– I like to experiment. And sometimes we
experiment on ourselves. Now I hope you can
see that– this is a line from a local
company called Inside Tracker, and in full disclosure,
I advise that company. But they’re the
only group that I’m aware of that has a true
scientifically-based algorithm to be able to estimate what
your biological age is. And so I said, sure,
analyze my blood. They’ve analyzed
thousands of people now. And so they took blood samples,
and you can see, I hope, that although I’m only– at the time I was 46 or so,
I was about 10 years older based on their algorithms. And they measure five things– glucose, testosterone, and a
few other things that basically correlate with longevity. And I was not looking very
healthy and I thought, this would be really
bad if I died young. [LAUGHTER] So I decided to do
something about it. And what I did was– first thing I did was, I was
more conscious of what I ate. And I lost some weight, I
lost about seven pounds, which didn’t hurt, OK? Full disclosure, that’s
one of the best things you can do if you have a
little bit of overweightness. But also what I did was, I
tried some of this NMN molecule. We had some that
was safe in mice and I was prepared to try it. And what you can see
over the next few months is that this company
came back with– they didn’t even know what I was
expecting, they just came back and they said,
your blood test now predicts that you’re
31.4 years of age. So I jumped for joy. This is fantastic. Now I put on a little
bit of weight since, but the point being is
that if this is true, then it is fairly easy to
give yourself some extra life, and that’s really what
we’re talking about today. And I’m very excited to hear
the next two speakers that will tell us even
more exciting things about their work in the
species we call human beings. So thank you very much. I appreciate that. [APPLAUSE] So now without further
ado, I want to invite Alex. Alex Touroutoglou is a
worldwide and renowned expert in human aging and I can’t
wait to hear what she says. [APPLAUSE] Thank you. Thank you very much. So it’s a pleasure to be here. I’m going to present
SuperAgers to you, and I think David’s father
is probably a SuperAger. Let’s look at the SuperAgers. Let’s see what are
the SuperAgers. We all know that the memory
and cognitive decline usually with aging. For example, with
the young adults, scores about a 13
on a memory test. Typical older adults
usually perform much worse. But there are some people
around 60 to 70 years old that continue to perform
equally or even better than young adults 40
years their junior. This unique group has
resisted the cognitive decline that is typical in aging. We call this group
the SuperAgers. We will start out by
describing what is a SuperAger. And I would like also
to show you today how their brains are different. As neuroscientists, we had to
gather the SuperAgers to come into the scanner, look
inside their brains to uncover their secrets. There are several ways you can
look at the brain using MRI. You can look at the
brain structure, you can look at the brain
networks, the brain activity, and you can look at
what parts of the brain become activated when
people perform a task. So I’m going to present today
three studies to understand the superaging brain. Study one will look at
the brain structure, study two will look at the brain
connectivity in SuperAgers, and study three will look at
what parts of their brains activate when they’re
performing a memory task. Let’s begin by describing
the definition of SuperAgers. One of the reasons why I
believe our studies are exciting is because we are focusing on
people around or just about– just after their
retirement date, mostly in their 60s and their 70s. And we’re interested
to see who perform– what older adult
is it that performs as well as young
adults in their 20s. Based on the
laboratory testing, we give them a memory
test, a memory test that includes 16 unrelated words. The challenge is
that older adults who will have to memorize this
list and later on recall– repeat this list
after 20 minutes. Most older adults will recall
after a delay between eight and 10 of those words. Young adults will
remember 13 or more words. SuperAgers will also
remember 13 or more words, and in some cases, they will
remember as many as all 16. So it is really
remarkable for SuperAgers, for this group that
is around 70 years old to have a
memory, sharp memory, the same memory as someone
four or five decades younger. So based on our
laboratory testing, we define SuperAgers
as those older adults who perform equally or even
better than younger adults 40 years their junior. First we looked at the
their gender and education and we found no difference. There was no difference
in neither gender nor education between SuperAgers
and typical older adults. In our study, it
turns out that we had 17 SuperAgers and 23 typical
older adults who did not meet the superior memory criteria. So next we asked, what makes
a SuperAger a SuperAger? So we looked at the structure
of the brain in study one. We used MRI. Mass General Hospital
is the first US hospital to establish a diagnostic
and research program specific to MRI. MRI uses strong magnetic
fields to create images of biological tissue– in our case, the brain. I present here a
schematic organization of the scanner and the control
systems that we are using. In addition to the
scanner, we are using a series of
amplifiers and transmitters that are responsible
for recording the data and for sending the MRI signal
into the powerful computers where we analyze our
data in our laboratory. In study one, we measured
the thickness and the size, the volume of gray matter. Gray matter is the
part of the brain where all the thinking and
sensing is actually happening. There are several ways that
you can display the MRI data on structural MRI scans. One way is to use
a volume template. Another one is a folded
brain or an inflated brain. I will be using both volume
and inflated brain to present– to show you the data. OK, so let’s look at the data. Let’s look what study one
showed about SuperAgers. We looked at their cortex. The cortex is the outer
layer of brain cells that is really important for
our critical thinking abilities. We knew from previous studies
that the cortex as well as other parts of the brain
typically shrink with aging. We compared the brain scans
for SuperAgers, typical older adults, and younger adults. And what we found is that as
you see here, the red blobs, we found all of these regions
were thicker in SuperAgers than in typical older adults. These are the areas where
there was more gray matter in SuperAgers. And it’s not just
a few regions, it’s distributed all
throughout the cortex. I group them based on their
function, and as you can see, those that are included
in the blue outline are important regions
for attention, and those that are included
in the yellow outline are regions that are
important for memory. Remarkably, some of these
regions were truly youthful. And when I say youthful, I
mean they were statistically indistinguishable
from young adults, as we will see in
the next slide. You can see here, the bar graph
shows the cortical thickness in these two example regions,
the medial prefrontal cortex and the mid-cingulate cortex. The thickness in SuperAgers was
the same as in young adults. It was thicker in this region
than typical older adults, but it was about the same with
the young adult. Same here in the medial prefrontal
cortex, this region showed full preservation. It was noticeably
thicker in SuperAgers than in the typical
older adult, but it was statistically
indistinguishable– comparable in size with young adults. As Hippocrates once
said, “It is far more important to know what person
the disease has than what disease the person has.” So we looked inside
each individual brain to better understand
the brain of SuperAgers. And here we are. Looking inside the
brain, we realized that if we measure the
size of brain regions, we can predict how the
individual is going to perform on the memory task. We measure the brain
size before the task, we’re able to predict
how that individual will perform on the task. You can see here that
this individual, who had the largest
hippocampal volume, performed among
the best in memory. And this individual,
who have the smallest hippocampal volume, perform
among the worst in memory. Hippocampus is a deep
brain region which is really important for memory. So the larger the hippocampus,
the better the memory. Summarizing the
data from study one, we saw that although memory
decline may be the rule, there are exceptions. SuperAgers show youthful brain
structure in important regions for attention and memory. The thicker the brain regions,
the better their memory performance. But in order to
understand the brain, it’s not enough to focus
on the brain structure. The brain structure is
not the whole story. You need to understand
its wiring as well. Brain activity is important
for understanding the brain because no brain
region is an island. Brain regions are
connected with each other, they communicate
with each other, and they are part of a network. And when regions are
part of a network, they ordinarily
talk to each other and they function together. A growing number of
studies have looked at the aging brain from
the perspective of networks and brain connectivity, and
there are several theories that have suggested that
cognitive decline in aging may be the result of disruptions
in brain connectivity. So we looked at the
brain connectivity and we wanted to compare the
SuperAgers to typical older adults, and again,
to young adults. And here are the data. As you can see
here in red-yellow, these are the regions where the
SuperAger were more strongly connected than the
typical older adults. There was no region in
typical older adults that had higher or
stronger brain connectivity than SuperAgers. So the SuperAgers
were more networked. Their brains were
more networked. Again, as we saw in
the anatomical data, you can see here that the
strength of connectivity in SuperAgers were noticeably
stronger than typical older adults, but it was actually
comparable in magnitude with young adults. We also looked for another
clue in the individual brain. Here, we measured the
connectivity in the region deep inside the
brain, the hippocampus and in the cortex, the
posterior cingulate cortex. And we found that SuperAgers
had stronger connectivity in these areas, and the
stronger the connectivity, the preserved connectivity
also predicted their memory performance. Stronger hippocampal
connectivity, better memory performance
for older adults. Taken together, the data
from study one and study two, we’ve established
that SuperAgers show youthful structure and
youthful brain activity. They do not have only
preserved neuroanatomy, their brain networks
are also preserved. But if you think of
SuperAgers as an extreme group from typical older
adults, it’s not enough to simply show
preserved anatomy and preserved connectivity, you need to
see how these groups are prone to memory
problem differently if there is a difference. You need to see what is the
difference between them when they are actually
performing the task. And that’s what study
three sought to do. So in study three, we measured
the brain activity in response to a task. We looked at what parts
of their brain light up, activate when they are
performing the memory task. So we put them into the scanner,
we give them a memory task, and we were watching
their brains. fMRI is the first fMRI
technique was discovered by Jack Belliveau in
1990 at Mass General Hospital and the
research facilities where we are actually
conducting our imaging studies. In 1991, the prestigious journal
Science published his paper and they also got his image of
the first scan on their cover. After that, the fMRI
became widely available and allows scientists
now to study the brain in a noninvasive way. The basic idea is that
you look at the brain and you try to identify
hotspots of brain activation in response to tasks. And here are the data. The brain maps here
show the hotspot– the regions of
hotspots of activation in SuperAgers versus
typically older adults. Before I talk about
what we do see here, the hotspots of
activation, let me just focus for a moment
on what we don’t see. And notably, these are the
regions that are traditionally involved in memory. SuperAgers and
typical older adults performed the memory
task in the same way in terms of memory regions. They activated equally
at the same degree their traditional
memory regions. The difference lied
in another region. The difference lied in
mid-cingulate cortex, a region that is implicated
in many functions, but importantly, for motivation. When this region is
being stimulated, it elicits the
will to persevere. So this means that
SuperAgers approach the problem differently
than typical older adults. They were more motivated,
they did not quit. And not surprisingly, when
we extracted the signal from this area, we found
that those individuals who activated the
mid-cingulate cortex more, they did better on
memory performance. So taken together, the
data from studies three, we found no differences in the
memory regions when SuperAgers and typical older adults
performing a memory task. But we did find a
difference in a region that is really important
for motivation, in what I call tenacity. This region is important
to push forward when you face difficulties
and you face a challenge. Summarizing the three studies
together, all of our superaging work, I wanted to
show you today what makes a SuperAgers a SuperAger? Well for starters, a young
brain in an older body. We’re trying to piece together
the puzzle of the superaging brain. It’s a puzzle that
is far from complete. We’ve seen that SuperAgers
have avoided that memory and cognitive decline. They show sharp memory
despite their age. They have youthful structure,
useful brain connectivity, and when they are faced
with a difficult task, they become tenacious. We believe that
understanding SuperAgers is the first step towards
understanding successful aging. If we can understand what
makes them SuperAgers and what makes them to remain
youthful memory abilities, then we are one step
ahead understanding what healthy aging might
mean for all of us. I’d like to close by asking
one important question– can you make a
person a SuperAger or are you born with it? And with that, I’d like
to thank you, and– [LAUGHTER] and
introduce Dr. Lipsitz to hear about all
the interesting data about healthy aging. [APPLAUSE] Thank you, Alex. Well thank you, Alex. I’m just going to take a second
to pull up my slides here. Well great, good
evening, everyone. I am a geriatrician,
which means I’m a physician who cares
for older patients, as well as a
clinical researcher. So what I’d like to do is
speak from the perspective of a geriatric doctor– that doesn’t mean that I’m
old, but that I study old– and share with you some
of the new developments in clinical research and aging. Curiously, aging
is a young field. A century ago, very few
people lived to old age. In fact, the average
life expectancy in 1900 over 100 years
ago was only 47 years. And as you’ve probably
heard in the media, now 10,000 members of
the baby boom generation, which includes me, are
turning 65 every day. In fact, that was
old news– now it’s 10,000 people
turning 70 every day. This means that older
people over age 65 will soon comprise 20% of our
population, and as a result, as you’ve heard, there are
enormous social, medical, economic, and ethical challenges
that will be facing us. But there’s a lot of
optimism, because there are a number of
opportunities, which I’ll share with you, to
apply advances in science and engineering to improve the
health and well-being of older adults. This just illustrates the
fact that the world is rapidly aging. You can see a variety of
different societies here, and Japan leads the list in
having the most rapid growth of the older population. But this is occurring in
the United States as well, and the estimates are that
by 2030, the number of people over age 65 will double
from about 35 million today to 72 million. And those over 85 are one
of the fastest growing segments of the
population, and that will double from about four
million to nine million by 2030. So this is a huge
change in our society. Currently we have about 13%
of the population over 65, but they account for about a
third of all hospital stays, and almost 50% of the
days in the hospital that a patient might spend, and
50% of the hours a physician spends with a patient,
costing Medicare $26 billion. So as you can see, aging is
us and aging is expensive. That’s illustrated here by this
story that says, I’m sorry, we’re bombarded
with aging boomers, so come back in about 20 years
for your health care system. Unfortunately, our
health care system has been slow in adapting to
this baby boom population. But the good news is that
life expectancy is increasing. The yellow line here
illustrates the life expectancy or the survival pattern
of people in 1900. And you can see, there
was a big drop-off actually before the age of
10 due to early childhood diseases, which we’ve now
conquered, pretty much. And as time has gone
on, more and more people are living to older age. We generally speak
of life expectancy as the number of years a baby
born today can expect to live. And you can see here in
these successive curves that life expectancy is
increasing over the years from 1900 to 2000. But another concept is
lifespan, and lifespan is considered the
maximum number of years a given species can live. And it used to be thought that
our lifespan really was capped at about 100 years of age. But as you’ve heard
from Dr. Sinclair, there have been some
very exciting advances that suggest that
maybe we are going to be able to increase the
lifespan as well as life expectancy. In fact, it seems also the older
you are, the longer you live. These are actuarial tables
that some of our actuaries used to decide how much
insurance we should pay, but you can see here that today,
a person about five years old can expect to live to about
82 if they’re a man or 86 if they’re a female. Curiously, women have always
lived longer than men. They are the stronger
sex, I must admit, this is true until
very late in life. So the older you are, the
longer you might expect to live. So an 85-year-old
today might expect to live to 93 if they’re
a male and the same age if they’re a female. So the key to this is
live to 85 and you’ll have a good chance of
living even longer. But that’s not enough. We don’t want to just
live to a ripe old age, we want to live to that
age without disability. And I think Dr. Sinclair
demonstrated this quite nicely in his slide, but the goal
of us in geriatric medicine and researchers in the
field are to decrease the duration of disability. So this top line really
shows the situation today. At about 55 years
of age or so, people begin to accumulate illnesses
that eventually result in more and more
morbidity or disability, and ultimately,
perhaps at age 76 or so, they might
experience death. One goal is to
extend the life maybe to 80, 90, 100 years of age,
but if we didn’t do anything about disability,
all that would do is extend to the
number of years, increase the number
of years in which we had to suffer with
disease and disability, and of course, that’s no good. So what we need to do is
shift to the right the time at which we might develop
disability, and as well as increase our lifespan. Ultimately, what
we hope to do is shrink morbidity–
in other words, delay any kind of illness, any
kind of morbidity or disability until the day we die,
and then suddenly drop off with a healthy
life the entire time. And that’s what Dr. Sinclair
and other scientists are now beginning to
show us that we might be able to do with some of
the new innovations in aging research. Well this lists some of
the challenges, though, that we all experience
in the cycle of aging. As you know, at age one,
the challenge is walking. By age two, it’s
keeping dry, you know? At age 16, it’s
driving; at age 20, the challenge is having
sex; age 30, having kids; age 40, working;
age 65, retiring. And then the cycle
begins to repeat itself. At age 70, having grandkids;
age 80, having sex; age 85 driving; age 90, keeping
dry; and age 95, walking. So this is the cycle that I
think we’re all familiar with. But as we age, there are two
problems that worry us all, and certainly, I think
it’s true that most of us worry about the loss
of memory and mobility, these are major, major problems
that we in clinical research need to tackle while we wait for
Dr. Sinclair and his colleagues to find a way of
curing all illness so that we can live a long life. So let’s look at these. Memory loss, of course, is
a very prevalent problem. Currently, about five
million Americans have Alzheimer’s disease, and
about a third of older adults ultimately die of Alzheimer’s
disease or other dementias. This is the sixth leading cause
of death in the United States, and for the first
time, our government is actually putting
a lot of money into studies to try to
tackle this problem. But the problem is not
just in the person who suffers from this
disease, it is also a problem for the 15
million caregivers who provide more than 18
billion hours of unpaid care to help manage their
relatives and friends who have Alzheimer’s or other dementias. In 2017, Alzheimer’s disease
cost the nation $259 billion, and this is expected to rise
to $1.1 trillion by 2050– huge problem. So what causes
Alzheimer’s disease? Well, we don’t really
know yet, but we do know that if you look
at the brains of people who have died of
Alzheimer’s disease, there are two proteins that
gather in the brain and cause damage. One of them on the left here
is the amyloid plaque, shown as this yellow schmutz here. And on the– technical
term, that is. And the right here is
neurofibrillary tangles, which are these dead
neurons that have in them a protein called tau. So one of the challenges
is, if these are truly the cause of
Alzheimer’s disease, we need to get rid of
these toxic proteins. So much of the work that’s
being done in laboratories around the world is to try
to think of new drugs that can actually sop up
these or prevent them from being deposited
so that we do not develop Alzheimer’s disease. But one of the
challenges is, you know, we can’t look at
the brains of individuals to try to see whether
we’ve been successful or whether they have Alzheimer’s
disease, because that would require a brain
biopsy, which we’re not going to do in living people. So we’ve been very fortunate
over the last decade or so to have scans, like the
MRIs you’ve heard about, but special scans in
which we can actually image these toxic proteins. And one of them is
on the left here, this was a PET scan
for Alzheimer’s disease that injected a Pittsburgh agent
it was called, because it was invented in Pittsburgh, that
can actually light up amyloid in the brain shown here in these
yellow and orange MRI scans. In people with Alzheimer’s, you
can see a lot of this amyloid, but in controls who are
normal, you do not see it. So now, having this scan,
we’re able to actually look whether new drugs can get rid
of these amyloid deposits, and much of the
research going on today is trying to get rid of these
amyloid deposits earlier in life before people
develop the disease. And on the right is
just another scan that looks at the ability of the
brain to use sugar or glucose, and you can see, a normal
person on the right has lots of activity,
lots of red and yellow, while the Alzheimer’s
patient loses that ability. We’ve been working
on many therapies for Alzheimer’s disease, and I
wish I could tell you we have a cure, but we don’t. In the meantime,
though, we need to be able to treat the disease. So there are many
therapies that might slow the progression of the
disease that are listed here. Some of them increase
a transmitter in the brain called
acetylcholine, and you’ve probably heard of
drugs called Aricept, Exelon, Reminyl that can do that. And they might slow
the progression– they’re not dramatic, but
they have some effect. And the same is true
of a drug called Memantine which can prevent
some of the damage in the brain. But something you all can do is
reduce your cardiovascular risk factors. Because we know that
the same factors that cause heart attacks
and strokes are also related to Alzheimer’s
disease and other dementias, particularly vascular dementia. So we need to treat
hypertension, treat high cholesterol, and treat
diabetes or prevent it in the first place earlier in
life to prevent these diseases. Dr. Sinclair mentioned
oxidative stress, we used to think that if
reduced oxidative stress in the brain, that might
reduce this disease, that has not been met
with much success. We also are aiming to
prevent the inflammation that these toxic proteins cause. And also, as I
mentioned, we are trying to develop drugs to
reduce amyloid or tau deposition in the
brain, and there are many drugs being
tested and many scientists are looking for vaccines to
sop up these abnormal proteins. But another thing
that we can all do is become involved in mental
and physical exercises. Do those brain tests that
the SuperAgers are doing. That might, in fact, enable
you to become a SuperAger. We know that the aphorism, “we
use it or lose it” is true. People who have remained
active throughout their lives are engaged in
cognitive activity tend to have less
risk of Alzheimer’s and other dementias, so
it’s very, very important to engage in activity. And one study I always
like to refer to is one that actually took
a group of older people from a community and invited
them to volunteer teaching children in elementary school
classrooms in Baltimore, this was called the
Experience Corps. These people who
came to the classroom and taught these young
children had brain scans actually similar
to what you just heard to look at
the brain activation before and after this activity. And they were compared to a
group of people just like them who did not participate in
teaching these children. And you can see, in the blue
areas are parts of the brain, using this functional
MRI, that were activated more in the
volunteers than those controls. And you can see on the
right in the blue lines that the activation during
a number of cognitive tests was actually increased in these
people who simply volunteered to work with children
in the classroom compared to the red,
who were the controls. So remember, use it or lose it. What you’re doing today,
sitting here and thinking, is really going to help you
give you a couple of extra years hopefully without
Alzheimer’s disease. So the second worry that
we all have, of course, are mobility problems, and
these are quite prevalent. About 30% of
community-dwelling older people fall each year, 50% of
nursing home residents fall, and this is associated
with lots of injury and costs of as
much as $31 billion. This is not a hambone, but
a human thighbone here– this is the
cross-section of a thigh of a healthy young person. And you can see the bone up here
with the marrow in the middle. And you know what
this yellow is? It’s muscle, and the fat is red. Keep that image in
your head, because this is the same cross-section of
a thigh in an 80-year-old. And what’s happened? They’ve lost muscle and
they’ve developed fat. Now we used to think this was
inevitable, that all of us develop this as we age. We used to think, shown here,
that muscle mass declines with age in all of us. But in fact, activity level
also declines with age, we all sit in rooms
like this all day long, and it is the activity level,
the sedentary lifestyle that is actually responsible
for much of the muscle loss– not all of it, but much of
it that occurs in older age. And the good news is
that resistance training can actually improve
muscle strength and muscle size at any age. We took a group of 100 frail
nursing home residents who were as old as 98
years of age and had them go through 10 weeks
of progressive quadriceps resistance training,
just lifting weights with their legs. And we found a 113%
increase in muscle strength, a 12% increase in walking
speed, a 28% increase in their ability
to climb stairs, but only a 3% increase
in the muscle area, so we got a big
bang for the buck. For that small amount
of muscle size increase, we got a lot of
strength increase. So it’s never too late. We should continue exercising
or take that pill David’s been talking about. [LAUGHTER] I won’t go there. So a common cause of falls
that we’re all interested in is multitasking. You know, you’re all– probably
some of you are probably doing it– taking pictures, walk– looking at your cell phone,
driving while texting– we multitask all the time. This man is walking
across the street while he’s reading the
newspaper, not a good idea. Multitasking we can actually
test in the laboratory by having somebody stand
on a balanced platform and measuring their
actual balance shown here, and this is what happens,
these are all the movements that you make when you’re
standing presumably still on a balance platform. We then ask that person to
do what’s called a dual task. They can stand here and count
backwards from 500 by threes, and when they’re
standing, and counting, look what happens
to their balance. They’re now swaying
all over the place. And what we can do with that
is draw a circle around this and look at the degree of sway. We can then compare
those two circles and compute what’s
called a dual task cost. So this is the cost of doing
two things at once– so texting while driving. And we can use that
cost as a measure to look at how bad your
balance is when you’re doing too many things at once,
when your brain has to control many things simultaneously. So we can actually
improve dual-task costs with a number of
different interventions, but one we’re using is
electricity and magnets to stimulate the brain. This is one of our subjects. You’ve all heard about
brain stimulation. This is deep brain
stimulation that’s used for Parkinson’s
disease, but we’re actually using transcranial
magnetic stimulation to try to enhance the
activity of the brain, or what’s called transcranial
direct current stimulation, just a little C-cell battery,
you know, attached to your head can actually stimulate
certain areas of the brain. When we do that, we
could look at a given individual– in this case,
it’s just a 72-year-old woman– and we can look at their
dual-task cost of standing or their increase in sway
during the balance test. We can then give them some
electrical stimulation of the brain and measure
the reduction in that cost. So this is a very exciting,
non-invasive intervention that people can do at home
that will hopefully eventually lead to a reduction in
falls and many older people. And I expect also to do
this when I’m slumping over my desk about 1:00 in the
afternoon feeling tired, just put a little
C-cell to my forehead. We did 10 daily sessions of
this transcranial current stimulation and showed that
it could actually improve the dual-task costs to balance. Well one final
intervention I’d like to share with you is about
vibratory shoe insoles to improve gait and balance. We developed a little insole
that can go into the shoe and it vibrates a little
bit– you can’t even feel that vibration– and showed that it was able
to improve walking and balance in older people. And this is based on a
physical principle called stochastic residents that says
that a little bit of noise can improve your
ability to sense things. Here, you can see
what the ground does on the bottom of your foot. You can see that here. This is just the
sensation of the foot as it stands on the ground. But when we superimpose
a little bit of noise, that sensation is enhanced. And by doing so, we can actually
improve gait and balance. Here is a picture of the insole,
it can fit inside your shoe and a little battery can
sit right on the laces here. And we can actually test
your walking on a little gait platform shown here. So as we walk somebody
on a little gait mat while they’re subtracting
7’s, you can see, here’s what their walking
pattern looks like, and it’s a bit irregular,
they stumble a little bit, take short steps, long steps. Later when we do it again
with the insoles turned on, you can begin to see a
more regular pattern, and here, we now
have improvement in the gait pattern,
and hopefully these will be developed in such a
way that we can prevent falls. So the good news is, there’s a
lot of positive interventions that might improve our
experience of aging. We hope to be able to reduce
disease and disability in old age, hopefully find
a vaccine for Alzheimer’s disease. I believe we will all be seeing
an increase in the retirement age and working to ripe
old age of 70 or 75. We’re developing elder-friendly
cities and housing options within cities that have health
care and services in the home so we can age in place and don’t
need to go to nursing homes, hopefully not go to hospitals,
and use personalized medicine to really emphasize our
own personal goals of care so that we can live a
healthy, happy life. It’s never too old for anything. Here’s a woman who’s skydiving
for her 92nd birthday. This, I’m sure, will be David’s
father in another few years. [LAUGHTER] So thank you all for your
attention and interest. [APPLAUSE] Do we have time for this? Yeah. All right, we have about
15 minutes of questions, thank you for sending those
in, those in the audience. And also, we have some
questions from around the world, our online audience. So we’ll see how
far we get, we’re going to try and keep our
answers brief given the time. So I have a question
at the top, and this could be for either of you,
tell me who wants to take it. The question comes in
from Bangalore, India. Wow. Would this research help people
who are already experiencing the onset of neurodegenerative
diseases such as Alzheimer’s? Or would it only
healthy individuals? Well, I’ll just say
quickly that much of the research with people who
already have later Alzheimer’s disease has not been
that successful, so many of the new studies are
looking at earlier disease. But it is very
hopeful that we’ll be able to perhaps develop
some ways of getting rid of these toxic proteins
and other causes of diseases even in late life. And much of our research,
though, while that’s going on is trying to
nevertheless improve the quality of
life of people who already have Alzheimer’s
and other neurodegenerative diseases. So I think while the
research is going on, we need to really focus
on the quality of life, even if people have
Alzheimer’s disease. OK, this one’s for Alex. What are the age ranges and
categories of SuperAgers, and what impact is there
of exercise and blood flow? Nice question. Well, SuperAgers in our study
were around their retirement– SuperAgers in our study were
around their retirement age. About 62 to 80 years old. They came from all
different walks of life. There was no difference in
education, no difference in gender as we said. Can we hear me now? Might have to hold it up. OK. Maybe– That’s good. Sorry. I was saying that they can– SuperAgers come from all
different walks of life. There was no difference
in SuperAgers and typical older adults
in their education or their gender. Exercise, exercise
has been shown to improve cognitive
function in older adults, and although we don’t know yet
whether SuperAgers are involved in more exercise, we can
predict is that SuperAgers are more active in their lives. Future studies will
need to systematically examine and follow older
adults longitudinally, and those that have developed
to SuperAgers and those that do not to see
their exercise pattern. All right. This is a question
for me, I think. How long before you see
NMN molecule becoming available to the public,
and are there any downsides? Well, we’re in phase one
clinical trials across the road here, and what that
means is that we’re just observing the safety. And then there’s phase
two and phase three and these take a few years
to get through at best. At worst, something will crop
up and we’ll be slowed down. So it’s not going to be
available as a medicine any time soon. A few years, maybe? If we are successful and lucky. That said, there are related
molecules that are available, being sold. And I can’t vouch for those
because they haven’t been fully tested in humans, but there
have been a few clinical trials with supplements,
and so far, they seem to raise NAD levels, which
is what we see in the mice. But are there any downsides? Basically, is there a risk? Of course, there’s always a risk
when you introduce a molecule into your diet. I mean, don’t quote me, I’m
certainly not recommending you do this, but I can
tell you for a fact that we haven’t seen any
serious downsides or even anything to worry
about in mouse studies. There’s a study at Washington
University in St. Louis, and they fed a
molecule called NR, which is a relative
of our NMN molecule– no, actually they also gave
NMN for a year, and the mice– side effect was that
they had slower aging and there was no
physical downside. But of course, a
mouse is not a human, and that’s why we’re
taking the time to do these clinical trials
to be sure that they are safe, because if we’re going to
be taking these molecules, you probably have to take
them for many, many years to have the
long-lasting benefits. All right, I’m
asking questions, OK. Are there any genetic
signatures for SuperAgers? That’s a very
interesting question. Perhaps we can collaborate,
David, to see what’s happening. There are no studies that have
linked genes to SuperAgers. This is really
innovative research, there’s a lot more
to be learned. I might just make a comment
that sometimes SuperAgers are confused with
centenarians, who are SuperAgers by the fact
they’ve made it to age 100. And there are many genetic
studies now looking at a variety of genes,
and there is no one gene, but there are some
interesting possibilities of genes related in
cholesterol metabolism, and depends on your culture
and your background. But it’s not just
the genes, it’s also the environment and
the lifestyle and behavior that influences whether you’re
going to make it to 100. Yeah, absolutely. Which leads us to our
next question which has come in from Facebook,
no country listed here– what is the correlation–
if any– between weight gain and longevity? That one’s a simple
one, I’ll take that one. Avoid weight gain. [LAUGHTER] In human studies and
in mouse studies, it’s very clear that
having excess weight accelerates aging– not just physically, but
even at the molecular level, we see those changes accelerate. Obesity will lead to increased
inflammation and a lot of chronic diseases that come. All right, I think that
that one’s pretty clear. Is mitochondrial damage
associated with aging? Yeah, the answer is
yes, but we’re not sure yet if it’s a driver
of aging or not. Probably it is because if
you damage mitochondria either in mice or
unfortunately, there’s genetic diseases,
mitochondrial damage, there are aspects of
aging that you see happen to those individuals. And so it’s probably
a part of aging, but it’s not the whole answer. And we don’t actually
fully understand why we lose our mitochondrial
function as we get older, but we are working on
reversing that in my life. Ah, so this is for
one of you two. Is brain activity related
to brain plasticity? That’s also another
great question. There are studies
that have shown that when you perform a task and
they measure brain connectivity right after you perform a task,
brain connectivity changes. The strength of connections
between the regions that were involved in
the task increases, which suggests that yes,
brain connectivity can be changed through
neuroplasticity, through experience. All right. A question from
the audience– why is it so difficult to
prevent aging in the brain? We don’t know if it’s difficult
to prevent aging in the brain. There certainly are changes,
we’ve seen that in the normals. It’s only recently
been studied to see how plastic or how much
plasticity, but we know the brain can change– that’s what this word
plasticity is all about. That’s why when
we use our brain, we can actually see improvements
in many of the functions that we perform. So I do think– I’m pretty optimistic
about the fact that we can affect the brain,
that we can change connections, we can improve it. But Alzheimer’s, when that
occurs, that’s a disease. So I think in normal
aging, yes, you can do a lot to keep
our brains healthy, but when we get a
disease superimposed on that, that’s
when degeneration begins to take place. And to date, we haven’t found a
cure, but an awful lot of work is going on to try to do
that, and a lot of money is being put into
research in this field. Also, just to add to that,
I agree with Dr. Lipsitz that this is an area
that is new and we don’t know if reversing brain
aging is difficult or not. Very few people have tried this. I can tell you is that
reversing aging in other tissues is extremely easy, and
it’s quite surprising how you can reverse
aging in just a week. One of the things that
we’re now learning is that it’s relatively
easy to improve blood flow in the brain,
and that could be a large part of
early stage dementia, vascular dementia
is a huge problem. And you know, whenever we make
a great breakthrough in science, what we end up realizing is,
it wasn’t as difficult as we thought, all we needed
to know is the answer, and that’s really what we’re– the reason we have a place
like Harvard Medical School. And I can tell you as well
that SuperAgers at least seem to have avoided
the fate of aging. They are not affected
by the typical patterns of aging that other older
adults have been affected. So it is a live example. Yeah. All right, this one might
be a little controversial. Does taking human growth
hormone help reverse aging? No controversy at all. No. [LAUGHTER] There’s been studies in the
past about human growth hormone. A lot of work was done
after surgery, for example, to see if it helped people
overcome the stress of surgery, and that showed that it
had more toxic effects than beneficial effects. Although we do lose growth
hormone, replenishing it has not been proven
to reverse aging. Well those are all the
questions that I have. I think– Grab some more. We have more? Barbara? Excellent. All right, OK. One member of the
audience wanted to know, is there any link between
Lyme disease and Alzheimer’s? Do we know? I am not aware– now Lyme
disease causes neural disease. It can cause peripheral
nerve problems, it could cause
problems in the brain, but those problems are
not Alzheimer’s disease. So to my knowledge,
there has been no link between Lyme disease
and Alzheimer’s disease. OK, I’m just going to read this
one literally, don’t blame me. All right. And Barbara, you gave it to me. All right, who wants
to tackle this one? Some loss of sexual
function in men as we age is not just age, but boredom. New stimuli, et
cetera, et cetera, may help reverse the loss
of function, yes or no? Yes. [LAUGHTER] I don’t know. OK. That actually is true. OK. Some things do get
a little slower, but sexual function still
is maintained in older age, but it sometimes takes a
little more stimulation. Let me just leave it at that. [LAUGHTER] We have a question–
what influences the pathophysiology
changes in the human body in order to trigger
the loss of NAD? Good question. Why does NAD go down with age? We don’t know for sure. Now what we do know is
that there are enzymes in the body that destroy NAD,
which seems like a silly thing to be doing, but often in
biology, when you want to alter the levels of a
certain molecule, you have some enzymes that make
it and others that destroy it and that gives you fidelity. Also, what I didn’t mention
that’s interesting about NAD is, it goes up and down
with the time of day, and the likely
reason that you jet lag is because your
NAD cycles are out. And so the answer to
that is, we don’t know, but these enzymes that destroy
NAD are a likely culprit, and perhaps we can
also develop drugs that would inhibit
that degradation and keep the levels higher. That was a good question. This is for Lou again. At what age group do we
visualize higher accumulation of amyloid plaques and tangles? Yeah, there is no
specific age, but there is a couple of points. One is, Alzheimer’s disease
can occur earlier in life, sometimes as early
as the 50s and 60s. This is early
onset disease, it’s a different disease,
perhaps, that does have some genetic
predisposition. But we usually see in our
practice and in our field is late onset of disease,
and that can occur any time– late 60s all through
the rest of life. So there are the– highest prevalence is probably
in the 70s and early 80s, but there is no specific
age for late onset disease. All right. Well thanks, Lou. Join me in thanking
the speakers, and thanks for coming. [APPLAUSE]


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