March 11, 2024 • 59 mins
Could we one day cheat death? Are we hurtling towards a time when science will be so advanced that aging can be prevented or halted in its tracks? Nobel laureate Venki Ramakrishnan takes a skeptical view in a fascinating exploration of longevity research. In Why We Die: The New Science of Aging and the Quest for Immortality, the acclaimed scientist delves into the complexities of aging and the pursuit of extending healthy lifespan.
A former president of the Royal Society in London, Ramakrishnan is a group leader at the Medical Research Council's Laboratory of Molecular Biology in Cambridge, England. He shared the Nobel Prize in Chemistry in 2009 for his work uncovering the structure and function of tiny cellular particles called ribosomes and was knighted in 2012.
In this interview with Peter Bowes, the molecular biologist provides a critical perspective on the dilemmas of aging research; questions the hype and financial interests linked to some aspects of longevity science; delves into the concept of compressed morbidity and its challenges, and explains his belief that dramatic life extension is not imminent.
Read a transcript: LLAMA podcast website
Photo credit: Kate Joyce and Sante Fe Institute
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Venki Ramakrishnan (00:03):
I don't think anyone has solved the
problem of keeping lifespanfixed, but keeping the healthy
part, extending the healthy part.
Usually both of them getextended.
So the part that you live inwith you know all the aches and
pains and diseases of all days,that fraction hasn't actually
changed, and so I think that isa serious dilemma or paradox in
(00:30):
the field.
Peter Bowes (00:30):
Why we die.
The new science of ageing andthe quest for immortality is a
fascinating new book by thephysicist and molecular
biologist and Nobel laureate,Venki Ramakrishnan.
Hello again, welcome to theLive Long and Master Aging
podcast.
My name's Peter Bowes.
This is where we explore thescience and stories behind human
(00:52):
longevity.
Born in India, VenkiRamakrishnan has enjoyed a
distinguished career.
A former president of the RoyalSociety in London, he shared
the Nobel Prize in Chemistry in2009 for the work he and others
did, uncovering the structureand function of tiny cellular
particles called ribosomes.
(01:13):
Over the years, his careerinterests have shifted in
emphasis from theoreticalphysics to trying to understand
how our bodies work at amolecular level and the process
we call ageing.
Why we die addresses thatquestion, but also explores why
we live, why some of us enjoylonger lives than others, and
(01:35):
whether some of the more recentefforts to extend lifespan live
up to the hype.
Venki, welcome to the Live Longand Master Ageing podcast.
Hello, pleased to be here.
Yes, it's really good to talkto you and we will dive into the
subject of your book, but Iwould like first of all to do a
little romp through your career,and that's a phrase I get from
(01:57):
your book, which you describe asa romp through recent molecular
biology.
But let's just start by talkingabout you and your extremely
long and varied career.
You grew up in India.
Venki Ramakrishnan (02:09):
Yes, I grew up in India, except for about a
year and a half that I spent inAdelaide, australia, when I was
eight and nine, and then I leftIndia at the age of 19 to get a
PhD in physics in Ohio, in theUS, and in Ohio is also.
(02:29):
I like to joke that the onlynotable thing I accomplished in
my graduate school in physicswas that I met and married my
wife.
But because it turned out thatI really wasn't so thrilled
about the problem I was workingon, and even during my graduate
(02:50):
work, I became very interestedin molecular biology, and so I
know you introduced me as aphysicist, but no physicist with
assault or her assault wouldconsider me one, because I left
right after graduate school andnever did any work in it.
And the reason was that I usedto read articles in molecular
(03:12):
biology and realized, you know,molecular biology was undergoing
this huge revolution.
You know DNA, the structure ofDNA had been done in the early
50s and based on that we hadthis huge explosion in molecular
biology.
We were learning about thestructures of molecules, of cell
(03:33):
membranes, and how the immunesystem worked, how the nervous
system, you know, wasconstructed and so on.
So I thought, well, this was agood move.
But I didn't know any biology.
So I went to graduate schoolall over again at the University
of California in San Diego, inLa Jolla, california, and I had
(03:56):
the option of getting a secondPhD.
But after two years I realizedI'd learned enough biology.
I had acquired a background inbiology and I knew how to do lab
work, and so, based on anotherarticle I read, I went to Yale
University as a postdoctoralfellow to work on the ribosome,
(04:19):
which is this enormous complex?
They're tiny by everydaystandards, but they're really
enormous in that they have abouthalf a million atoms and
they're the machines thattranslate our genetic
information into the proteinsthat those genes code for.
So all the thousands ofproteins in ourselves that
(04:42):
actually make life, actually doits thing are made by the
ribosome using geneticinformation.
So every gene codes for aparticular protein, and so that
got me into the ribosome.
And then, throughout most of mycareer, I've worked on one or
(05:03):
other aspect of the ribosome andeventually we and others ended
up solving the atomic structureof the entire ribosome, and that
allowed us to figure out how itactually worked.
So of course it's an ongoingprocess and we're still working
on the ribosome.
(05:24):
Now the aging thing came aboutfor two reasons.
One is the ribosome is verycentral and you can think of all
the proteins in our cell, thethousands of proteins in our
cell.
Each one is doing its part andthey all have to work together
and proteins have to be made inthe right amount and they have
(05:45):
to be made at the right time.
If they're no longer needed,they have to be degraded.
So you think of it as acomplicated orchestra and
there's a lot of things in thecell which control when the
ribosome starts making proteins.
It checks the quality of theproteins made by the ribosome.
(06:06):
There are all kinds of checksand balances.
If the wrong thing is made orif it's defective, the cell has
ways of getting rid of it and itturns out this process breaks
down during aging and one of thechapters in my book it's called
Recycling the Garbage and it'sabout a field called
proteostasis which is aboutprotein turnover and quality
(06:31):
control.
It's very, very central to myfield of how the ribosome does
its thing.
So I had this peripheralinterest, even though I myself
don't work on aging.
The other is that as amolecular biologist I became
alarmed by the increasing amountof hype in the aging field and
(06:51):
I think a lot of it is driven bymoney.
You know there's lots ofprivate money.
A lot of billionaires areworried about aging and dying
and they're investing heavily inaging research and this is
distorting the field and leadingto wild claims.
There's also a lot of money inaging.
As people get older they'reworried about getting old and
(07:15):
dying.
They want to sort of postponeit and stay healthy.
So they're susceptible to allsorts of things.
People that people want to sellthem.
So I think I thought I'm closeenough to the field but not in
it, so I don't come with anyparticular biases and at the
(07:40):
same time I can actually readthe primary literature and so on
.
So I thought I would distillwhat is going on and try to give
the reader a sense of you know,what are the things that make
us age and what, if anything,can we do about them.
And finally, in my last coupleof chapters they're a bit
philosophical about what wouldbe the implications if we just
(08:03):
prolonged life and so on.
So that, in a nutshell, is sortof what got me into the book
and what the book is about.
Peter Bowes (08:10):
Yeah, and that's really interesting.
And I'm also wondering if theaging process, as it is
affecting you as an individual,like it affects all of us, has
also helped focus your mind.
Yes, you've got yourtheoretical, you've got your
scientific background and, asyou say, you are able to dive
into this subject in a certainamount of depth.
(08:30):
And I'm thinking also from apurely personal perspective.
Venki Ramakrishnan (08:35):
Oh yeah, I say in the beginning of the book
that you know one thing thatwould perhaps well let me back
off a bit.
There are lots and lots ofbooks about aging, and they fall
into many categories, you know.
So a number of books are abouthow to age gracefully and how to
accept the end.
You know things like that.
(08:56):
So that's one sort of category.
Another is you know about, youknow how to stay healthy, you
know exercising and doing thingsthat help, and you know those
are sort of self-help books.
Then there are books about, youknow, the biology of aging, and
these also fall into a coupleof categories, you know
(09:17):
somewhere.
Written by journalists, you know, and some of them have done a
good job, but they're not sortof equipped to be very critical
about the literature or reallydigest it and see what its
limitations are, and so theyoften rely on interviews and
(09:38):
chats with people you know toget a feel for what's going on.
And of course, those peoplethey talk to may have their own
biases.
And then some of them arewritten by scientists.
But these scientists often havesome vested interests, they
have companies, they haveanti-aging companies, and so
they're pushing a particularpoint of view, you know, and
(10:02):
often I would say, they'resomewhat biased towards their
own.
You know, whatever it is thatthey're sort of stunning.
So I say in the book at thebeginning that you know one
thing you can say about me is Idon't have any skin in the game.
I'm not I'm neither directly anaging researcher, so I don't
(10:22):
have preconceived biases.
And you know scientists also,once they have you know certain
theories and stuff that they'vepublished, they're reluctant to
back off.
You know from them.
You know they become sort ofvested in their own beliefs as
well.
And but the other is I don'thave any financial interest in
(10:42):
aging.
So I said I have no skin in thegame.
But then I point out of coursethat's not true for the reason
you mentioned, which is we allhave skin in the game because
we're all worried about agingand dying.
So in that sense you know, likeeverybody I have, I'm concerned
about it.
Peter Bowes (11:00):
And the fact that, as you say, some scientists have
and not all scientists.
Some scientists in this fieldare very pure, if you want to
use that word, but some do havevested interest and of course
that only adds to the to thelayperson, and I like to think
that this podcast is aimed atabsolutely everyone.
I try to not use the acronymsand boil everything to a level
(11:21):
that we can all benefit from.
But yeah, there are so manyvested interests.
It just adds to the confusionof people who are genuinely
interested in their agingprocess and their longevity but
then think, well, whichdirection do I go in?
Do I go down this veryspecialist diet route, or do I
adopt this kind of exercise, ordo I need a certain exactly?
Venki Ramakrishnan (11:42):
there's so many things being pushed, and so
what I've tried, you know, justto give you an illustration, in
the last 10 years alonethere've been over 300,000
papers published on aging okay,primary paper now, nobody could
read any of them.
You know all of those becauseyou know, just to read a
scientific paper, even if youwant to just read through it
(12:04):
without really thinking about it, takes at least a couple of
hours, you know, and probablylonger if you really want to
digest it.
So of course, I've had to behighly selective, and so what
I've tried to do is ask, youknow, what are the key advances
and and what are the key factorsinvolved in aging.
(12:25):
And I've tried to construct inmy book, you know, to try to go
from the very simple.
So I start at the molecularlevel.
So start with, for example, dna, you know, which contains
information that really, youknow run is responsible for the
program, the program of life,the program to sell.
(12:47):
And so I start with DNA, then Italk about how DNA can be
modified, then I talk aboutthings that affect DNA, then I
talk about what DNA makesproteins and how these proteins
interact and how the proteinshave to be recycled and how, if
proteins clump together, you getdiseases or aging like
Alzheimer's.
You know so.
And then I talk about thingsinside cells, like large
(13:10):
organelles, like mitochondria,which really it's amazing when
you and I try to also give a lotof history, how we found out
about this.
You know characters who youknow, some of them really weird
characters who made bigdiscoveries, and so the
hopefully the reader will go onthis voyage and by the end come
(13:35):
out with some broadunderstanding of the whole sort
of broad background of biologyof aging.
And the idea is that next timethey see a report on some huge
advance in aging according tothe headline, they'll be able to
judge, because they can relateit back to the biology that they
(13:59):
picked up from this book andthey can tell is this a real
advance or have there beenothers like this before which
have sort of fizzled out, or isthis just one more thing or is
it incremental?
You know they'll have a muchbetter sense of how to navigate
this.
You know constant, constant.
Peter Bowes (14:18):
You know drumbeat of, you know aging advances and
what was interesting to me is,essentially, this is a book
about living.
It's about living as well as wecan within the constraints of,
let's say, an average lifetime.
It's not about eternal life,it's not being immortal, it's
not living forever.
(14:38):
It's about living, but youactually start by analyzing
death and what it is to die.
Venki Ramakrishnan (14:44):
I'm just curious as to why you took that
approach yeah, because you know,if you want to talk about dying
and aging, you have to actuallyask what do you mean by death?
You know, and what do you meanby aging?
And just to give you a verytrivial example, when you die,
you know you have over atrillion cells in your body.
(15:05):
Most of them are still alive atthe moment of your death.
That's the amazing thing, youknow so.
So what do you mean?
You're dead, you know all thosecells are still alive.
In fact, after you die,somebody could take your heart
or your kidney and and donate itto some recipient who needs it
right, and people have done that, you know.
(15:25):
People go and liver transplants, kidney transplants, heart
transplants, etc.
So you know what do we meanwhen we die?
Well, what it means is that wedie as an individual.
An individual is somebody whofunctions as a unit.
So the collection of the cellsthat make you function as an
(15:48):
individual, that collection, isno longer working as a coherent
whole, and so that's when youdie.
And typically nowadays, mostplaces define death by brain
death.
Okay, in the old days, you know, if your heart stopped, you
were considered dead, but thenpeople figured out how to
(16:08):
resuscitate you, you know withCPR and so on, and so they felt,
oh, that's not a gooddefinition.
So then it went to brain deathand even brain death.
You know, the exact details areslightly different and I point
out in the book that those caseswhere, especially in the United
States, the definition of deathin one state is not the same as
in another state and there wasa very famous case of a young
(16:31):
woman who died and I think inCalifornia, she declared death
but her family she was not deadby the standards of New Jersey
and so her family, you know,appealed and got her body
transferred to New Jersey andkept her alive by New Jersey
standards.
And then, you know, eventuallyshe died and you know, she was
(16:53):
in a coma.
And I think you know it justgoes to show you that defining
death is not not trivial andit's also, I point out, at the
other end, defining, you know,when a person's life begins.
It's also quite complicated,you know, is it at the moment of
conception, is it at the momentof implantation?
(17:15):
Is it when the embryo reaches acertain stage?
You know, is it when the fetusis viable?
I mean, these are notnecessarily scientific questions
, they're, you know, social andcultural questions as well, and
that's why we have this.
You know, big polarizationabout abortion.
Peter Bowes (17:33):
It's about arguing about when life begins, you know
and you write about compressedmorbidity which as an expression
, as a, as a phrase, I think iscrucially important.
Venki Ramakrishnan (17:45):
If you understand and get what it means
and I look to just explain yourunderstanding very interesting
concept, and so the idea ofcompression or morbidity is that
you live healthily for nearlyall your life and the period
(18:05):
when you're sort of sufferingdebilitation and decrepitude of
old age is very, very short.
So that period of morbidity iscompressed to a very short
period.
And so the idea is you stayhealthy all your life and then
suddenly, you know, collapseokay, within a very short time.
(18:26):
And the person you know whofirst coined the phrase freeze,
he said that look, this is alittle bit like the one horse
shea.
He quotes a poem by OliverWendell Holmes, from the thing
from the 19th century.
A shea is like a is a one ortwo horse carry, one or two
(18:47):
person carriage.
And he said, the one horse sheain the poem is constructed so
that all its parts wear out atabout the same time.
So nothing ever, it's neverdefective, you know, because all
the parts are going along atthe same time.
And this farmer is riding along, and one day he's riding along
(19:08):
and suddenly he finds himself onthe ground in a heap of dust
because the entire carriage isdisintegrated in front of him,
right under him.
Now that would be the equivalentof compression of morbidity,
because it has a paradox whichis if you're healthy, why would
you suddenly die?
You know all your organs arehealthy, you're feeling great,
(19:30):
well, why would you die?
And the reality is that almosteverything that has helped us
stay healthy for example,statins for cholesterol or blood
pressure medication to preventhigh blood pressure, or, you
know, diabetes drugs, you knowmetformin and things like that
(19:50):
All those things that havehelped us against diseases of
old age and helped us stayhealthy they have all
effectively prolonged our lives.
So the period that we areactually, you know, suffering
from the disabilities of old agehas not changed as a fraction
(20:12):
of our lives.
So, in fact, because we'reliving longer, you could argue
that we're actually spendingmore years, you know, with all
these aches and pains anddisabilities of old age, and you
can see that.
You know nursing homes and carehomes for older people.
It's a booming business, youknow, because more and more
(20:32):
people are going into them andthey're going, you know, living
longer.
So my I say in the book,compression of morbidity is a
very worthy goal, but it's notclear yet how we can achieve it.
Okay, because you know what wemay do is simply prolong life
and at the end, everything's notnecessarily going to break down
(20:55):
at the same time and, you know,as things start breaking down,
well, then you have yourmorbidity, okay, and so it's a
complicated problem.
The one thing that suggeststhat there's some hope for it
comes from studies ofcentenarians.
So I communicated with TomPearls, who's a world leader in
(21:16):
this area, and he has hisstudies show that people who
live especially 105 or 110 theseare what are called super
centenarians.
You know even centenarians ofpeople who live to be a hundred.
So, but these semi and semi,super and super centenarians,
(21:38):
they turn out to have very shortperiods when they're actually
sort of ill or, you know, frail,and they they often tend to
have almost none of the diseasesthat many people have as they
get older.
So they're very healthy formost of their lives and have a
very short period of sort ofwhat I call illnesses of old age
(22:01):
.
So that suggests that maybe,you know, if we can find out why
these people have somehowmanaged to live healthily for a
very long time and then, youknow, suddenly die, that would
be something that would be worthlooking into.
Peter Bowes (22:21):
And I think, just to emphasize the point, the best
example I can think of ofsomeone achieving a compressed
morbidity in modern times wasQueen Elizabeth.
She died, yes exactly she wasworking right to the very end.
Venki Ramakrishnan (22:37):
Yeah, and actually you know her husband,
prince Philip, was also veryhealthy until you know, just the
last few years of his life.
So perhaps you know peopleshould sequence their genomes
and see in their lifestyle.
Of course you know, you have torealize they also had the very
(22:57):
best environment and medicalcare and so on so it's perhaps
not a very fair comparison, but,on the other hand, it does say
something about, and they didn'tlive past a hundred.
Neither of them live past ahundred, so they're not, in a
sense, the most extreme of thecases, but it's a good point.
Peter Bowes (23:18):
And I think it's also interesting just non-famous
people that I have known ofwho've got to a great age.
What's interesting to me isthat they often achieve that,
most times achieve that withoutthinking about it, they just get
to a great age and they livetheir lives.
But then you, sometimes you diveinto the way that they've lived
their lives, whether it's beingtheir diet, their exercise
(23:39):
regime or, in many cases, theirsocial connections, their social
circles and the people thatthey've had around them at a
great age.
I think these are all thethings that play into that
ability to live long and to livewell.
Venki Ramakrishnan (23:53):
Yeah, so I point out in my book that Tom
Pearls has a website calledliving to 100.com and you can
fill out all sorts of thingsabout yourself and your habits
and you know your health history, and it'll tell you, you know,
how long you can expect to live.
And I do fairly well, becauseone of the things apparently is
(24:16):
if you have a parent who livedvery long, like in their 90s,
that somehow improves yourchances for genetic reasons
alone.
I have a father who's 98 yearsold.
He's well, he's going to turn98 this Saturday and he's still
going strong.
He, he does his own laundry andis cooking and until a few
(24:38):
years ago he would go off, youknow, on long walks and shopping
and so on.
And he still walks, you know, acouple of miles.
So you know, I don't knowexactly what it is about him,
except I think he has a zest forlife.
I think maybe you know that'squite important, but of course a
(25:00):
lot of it is due to somecombination of genetics and diet
and habits and so on.
Peter Bowes (25:07):
I think that factor that you mentioned of people
that do their own gardening andlaundry and household chores
until they achieve a as they'reachieving a great age, is
important.
I mean you could characterizeit as movement.
It doesn't really matter asmuch as you do.
Yes, absolutely.
Venki Ramakrishnan (25:23):
And using your brain.
I mean when you're cooking ordoing, you know somewhat
complicated tasks.
You know it's more active thanyou know if you're simply
passively receiving.
You know watching television orsomething, and you know.
So of course this is allanecdotal, but I think you know
these people who studycentenarians, like Tom Pearls.
(25:44):
They're looking systematicallyat you, know what are their
habits, what are their healthhistories, and then they're also
going to sequence their genomesand also sequence their you
know, methylation methylonesbecause DNA methylation is a
modification of DNA that'ssomehow related to aging, and
(26:07):
they could see other methylationpatterns, these tags on their
DNA as they age, but they'redifferent from people who don't
live as long.
So there's a lot of informationto be gained and we'll learn
more about that as these studiesprogress.
Peter Bowes (26:25):
You cover in the book, caloric restriction, which
I think, if you look at thescience, there's perhaps some of
the most solid science behindthe idea that a certain amount
of caloric restriction, reducingthe amount of calories that you
consume on a daily basis couldhelp you live longer and better.
And the dilemma, of course, fora lot of people here is that
(26:48):
many people prefer quality oflife, and quality of life does
not involve caloric restrictionover quantity.
Ultimately, the number of yearsI point out, you know.
Venki Ramakrishnan (26:59):
So the evidence for caloric restriction
is quite good, which is caloricrestriction is when you give an
animal or a person just enoughcalories and nutrients so
they're not malnourished.
So just enough and no more.
And that in studies on manydifferent species, all the way
(27:24):
from worms and flies to mammals,has shown to improve lifespan
compared to an ad-limitum dietwhere they're fed as much as
they want.
You know the food they can eatas much as they want.
But some critics have pointedout it's not a fair comparison
because an ad-limitum diet isbasically unnatural.
(27:47):
You know, the idea is we neverhad an ad-limitum diet until
modern times when food becameplentiful.
And so they say well, you couldjust as well conclude that an
ad-limitum diet is really badfor you, you know.
And that if you don't, you know, if you restrict your calories
(28:08):
it's better, but it doesn't haveto be so extremely restricted.
And there are also studies onintermittent fasting.
You know people say if you fastfor 16 hours at a time or eat
only in a five-hour window, thatthat can, you know, that can
help, and that too has beencontested.
(28:28):
So I point out, in the book,for many of these claims there
are also counterclaims, and weneed to be a little cautious
about how good it is.
However, there's no questionthat, at least compared to an
ad-limitum diet, which is eatinga lot and eating as much as you
want, a calorically restricteddiet does better.
(28:49):
And so the question is then why?
And this has led to thediscovery of these
nutrient-sensing pathways.
Well, actually I'm saying thatwrong, because the
nutrient-sensing pathways didn'tall come out of aging research.
Only one of them did, but theother one was a complete
accident, which is the Torpathway.
(29:11):
And it turns out that thispathway senses nutrients, and if
nutrients are plentiful, itdoes one thing it turns on
protein synthesis and it shutsdown degradation and recycling
of proteins.
On the other hand, if nutrientsare reduced, and even if very
(29:32):
specific nutrients are reduced,so you may get a lot of calories
, but you're missing certainamino acids, that too can have
an effect.
And what it does is it shutsdown what I call initiation, the
beginning of protein synthesis,so it prevents the ribosome,
which is my molecule, fromstarting to make proteins, and
(29:55):
so you stop making more proteinsand at the same time, you turn
on these pathways which areinvolved in removing what I call
the garbage garbage recyclersof the cell, these things called
phagosomes, which take thingsto the lysosome, which is an
organelle which is like a giantrecycling center where things
(30:17):
are broken down and recycled.
So there's lots of things toconnect the biology with these
broad studies, observationalstudies like what does diet do
to your health?
And that's another fascinatingthing how we're able to connect
the underlying molecular biologyand the detailed physiology of
(30:42):
the cell to broad things likediet.
Peter Bowes (30:46):
And I think what it is valuable to look into and to
analyze is that some of theseinterventions whether it's a
calorically restricted diet orsomething else that may
emphasize may impact yourlongevity, the number of years
that you live, and it also hasan impact on how you live now,
which could well influence howyou live in years to come.
(31:09):
But I think for a lot of people, living now is crucially
important and just by speakingpersonally as an element of
caloric restriction makes mefeel actually good, makes me
feel better, makes me feel alittle bit lighter, makes me
feel more energized, and I thinkthat could potentially help me
live longer.
Venki Ramakrishnan (31:28):
Yeah, so the fact is that these animals on
calorically restricted dietsthey're not lethargic, they're
actually quite active.
I think you're frozen, I'm notsure.
Are you hearing me?
Peter Bowes (31:43):
So I had indeed frozen the internet letters down
.
So we're actually picking upthis conversation 24 hours later
, internet restored.
Thank you for sticking with us.
So, let me just return to thepoint that you were Actually
just making.
We were talking about calorierestriction and the impact on
(32:03):
especially laboratory animals.
When we look at mice, thosecalorie restricted mice are not
lethargic, they're veryenergetic.
And you see it, don't you inthe mouse wheel in terms of how
they, and it's the same.
Venki Ramakrishnan (32:15):
It's the same with worms.
You know, when these firstmutants, these aging mutants,
were discovered in worms Again,the worms were.
You know Cynthia Kenyon calledthem frisky.
You know they were movingaround and they behaved a lot
like younger worms, so it wasn'tas if they were kind of living
longer, but sort of in adoddering state.
(32:37):
And so there is something aboutit also being fairly healthy.
I wouldn't say caloricrestriction comes with no
effects.
You know people under extremecaloric restriction that is a
very rigorous kind, which justenough to keep you alive and not
(33:01):
malnourished they do havethings they feel cold, they have
loss of libido, they're slowerto heal wounds, typical things
like that.
So it's not entirely, I wouldsay, without cost.
And the most important thing isvery hard psychologically to
(33:23):
keep it up.
And that is, if you take micethat have been caloricly
restricted and they're doingfine, you would think they'd be
happy doing fine, but as soon asyou allow them to eat as much
as they want, they gorge away.
So there's something about ourevolution we didn't grow up in a
(33:47):
time of plentiful food, so wesomehow want to put away that
food.
And so I think there is aquestion of how viable is this
as a strategy?
There is also the question ofpeople are always comparing
(34:08):
caloric restriction diets orthese intermittent fasting diets
with a sort of more liberal,almost all-you-can-eat diet.
Certainly, with animals it's anall-you-can-eat diet.
Now it could be that all youcan eat is one extreme and
that's not great for you, but itcould also be that maybe eating
(34:29):
in moderation and eatinghealthy food, balanced food, is
perhaps almost as good.
I don't know if anybody hasdone that comparison.
The one comparison is withstudies on chimpanzees.
There was a group at NIH and agroup at Wisconsin.
The Wisconsin group definitelyfelt that the restricted
(34:52):
chimpanzees were better off, theNIH group not so much, and the
main difference was that thecontrol diet of the Wisconsin
monkeys was much richer, and sothe control animals there did
develop all the symptoms ofoverindulgence.
(35:14):
I forget all the details, butthey did have many of what we
call diseases of excess and notso much in the NIH group.
And that suggests there may bea happy medium and moderation
(35:35):
and not overindulging isprobably and having a healthy
diet.
Peter Bowes (35:42):
Moderation is always the word that I come back
to when I'm discussing this,and to some people it might be a
boring word.
Moderation doesn't soundexciting like intermittent
fasting or no, but it'ssomething we can live with.
Well, yes, exactly Something wecan live with.
Exactly, and I think the pointis that, yes, there are lots of
fasting regimes.
(36:02):
Some may be difficult tosustain long term.
There is some evidence that acertain amount of caloric
restriction could be beneficialfor us.
But if you look at, if youapply this to humans and you
look at the way most people,especially in the Western world,
eat these days, if you look atthe extremes, the fast food,
look at television advertising,billboard advertising of food,
(36:26):
that is the excess extreme.
Which points to me.
It shows to me that, yes, thereis a happy medium, there's a
moderation, and the challengeseems to be to persuade people
that moderation which isn'textreme is potentially very good
for us.
Venki Ramakrishnan (36:43):
Yeah, and also I feel moderation is much
more sustainable than having anextreme calorically restricted
diet, which would be much harderto follow.
I mean even and I thinkmoderation also carries fewer
risks of some of the downsidesof a highly restricted diet.
Peter Bowes (37:04):
Let me just change direction a little bit.
The whole principle ofevolution is or at least one of
the principles is survival ofthe fittest.
Evolving over many, many years,it's the survival of the
fittest principle that governsthe way that we evolve.
So I'm curious why evolutionhasn't created a human being
(37:25):
that evolves to live longer andstay healthy for longer.
Venki Ramakrishnan (37:30):
Right, but that's because we think of
fittest as the fitness of theindividual.
But you know, fitness is, inevolutionary terms, is defined
more as being successful atpassing on your genes, and so
every species has to have thisbalance.
They have to have a balancebetween being able to procreate
(37:53):
successfully, producing enoughoffspring that their genes live
on in their offspring, versusliving longer.
And at some point there's no.
If you've succeeded in livinglong enough to pass on your
genes, evolution doesn't carehow long you as an individual
(38:16):
live, because the genes survive,and that's what's selected for.
Of course, genes, you know youselect for the Genes are what
are selected for.
But of course genes don't existin a vacuum.
They exist in individuals.
So the individual has tosurvive and be successful enough
at procreating, and this isperhaps why different species
(38:38):
have very different lifespans.
So I'll give you a broad ruleof thumb among mammals the
larger the mammal is, the longerlived it is on average.
They're outliers and I discussthem in the book because the
outliers are actually veryinteresting.
We could learn from them.
In fact, humans are an outlier.
We live much longer than wouldbe expected for someone, our
(39:03):
species, our size.
But you take mice.
Mice live for about two years.
Now why don't mice live for 300years, you know, like a whale
or a shark or something?
And it's because there's noadvantage to a mice, because
mice would get eaten or starvedlong before that.
So there's no advantage forevolution to allow mice to
(39:28):
evolve, mice to live very longor to age more slowly, because
they'd die of external causesthat have nothing to do with
aging, like predators.
And so smaller animals alsohave a higher metabolism and in
fact it's metabolism that's morecorrelated with age.
So faster than metabolism, theshorter the life.
(39:51):
So I think my chapter is calledLive Fast and Die Young, or
something like that.
And so evolution is, for eachspecies, optimized fitness.
So if you have a chance to livevery long, then your metabolism
is slower, then you take longerto procreate.
(40:14):
There's an advantage to livinglonger If you're a short animal,
fast metabolic rate, fastgrowth, very quickly get to
puberty and procreation.
There's no particular advantagein terms of evolution in having
that species live longer.
Now there's a curious thing Ipoint out in the book about bats
(40:36):
.
So bats are about the same size, or even some of them are even
smaller than mice, and yet theylive.
You know, a bat has lived for40 years.
I mean, that's an amazingrecord for such a small animal,
and that too has an evolutionarybasis.
So bats can fly, so they'remore easily able to escape
(40:59):
predators, and it turns out thatanimals that can fly are
generally longer lived thancomparably sized animals that
are terrestrially bound, andthat again makes perfect
evolutionary sense.
Peter Bowes (41:15):
So in human terms and we kind of touched on this
at the beginning of theinterview there are those in the
longevity industry, if we cancall it that, that aspire to
live to a very great age,whether it's 120, 180, or even
much, much longer than that, andthere are some that believe
that within our lifetime.
(41:36):
So let's say in the next coupleof decades that the science is
going to evolve so quickly thatit is going to make that
dramatic life extension possible.
Venki Ramakrishnan (41:46):
What do you think?
Well, I don't think anybody canknow.
If you were to ask me myopinion, I would side on the.
I would come on the side ofpeople like Jay Olshansky and
others who believe that Ourcurrent lifespan is pretty much
fixed and to overcome it willtake much longer.
(42:09):
Okay, it'll take some realbreakthroughs in aging research,
and part of the problem isaging is not one thing.
I doubt that there's going to bea magic bullet which will say
if we do this, we're going tosolve aging, and I think aging
is highly complex.
There are multiple, almostparallel strands that go into
(42:34):
aging, and it's going to takesome time to sort of pick
through all those strands andcome up with a real solution to
aging more slowly, Even in ourindividual selves, our organs
age at different rates, asjudged by various biomarkers and
(42:56):
so on.
So the idea that there'll beone magic bullet and that'll
solve aging, I don't buy it, andso it's really a question of
opinion, I admit.
My opinion is that it's goingto take a while, and long before
that happens, we need a numberof other advances to be made.
(43:19):
Now, of course, the moreoptimistic people will say well,
look at the rate at whichknowledge is exploding and we'll
have AI and genomics and we'llfigure out all this stuff.
I don't buy it, but I can't sayas a scientist, I can't say
they're absolutely wrong.
Okay, that is not.
(43:40):
I mean, there are a number ofcharlatans in the business, but
this is not a charlatan-likequestion.
This is a real question onwhich I think serious people
could disagree.
Now one serious scientist,Stephen Ostad, actually made the
bet with Ostansky about whethera person who lived to be 150
(44:05):
years has been born already ornot.
And they made a bet and I thinkthe bet was $150 or something
which they calculated wouldbecome $1 million in 150 years,
although I don't know what $1million would be worth then with
inflation.
But anyway, I think they don'tdisagree about the fundamental
(44:28):
biology.
I think they disagree aboutwhether these advances will come
in time for someone born now,before they reach current life
expectancy, and I think thereare others who believe that
there's a constant race.
So we start aging, but scienceadvances and by the time they
(44:53):
get really old, we'll be able toextend their lives another 10
or 20 years and then, by thetime that goes by, we'll be able
to extend it again another 10or 20 years, and that's how
they'll do that.
And the extreme view of this isthat we could live a few
hundred years already because ofadvances.
I think those people are, tosay politely, blind optimists.
(45:17):
But that's, as I say, a matterof opinion.
Peter Bowes (45:24):
Yeah, and I think, and would you agree, that
perhaps some of thoseserious-minded researchers who
genuinely believe that we mayhave extreme life extension at
some stage and are doing goodwork in that area, that at least
some of their work mightactually help us now and might
benefit us in the next decade ofour lives?
Venki Ramakrishnan (45:47):
I think the really big advantage to aging
research is that it will helpwith what I call the
disabilities or the decrepitudeof old age.
We have inflammation.
I'm 71.
I'm saying only because it'stoday.
(46:08):
A generation ago I'd be readyto die, and so I'm 71.
I have been fairly active mostof my life, and now I have joint
pain in my shoulder and kneebecause of osteoarthritis Clear
disease of inflammation in aging, and I even describe it in the
(46:28):
book.
And so if somebody were to lookat what causes this
osteoarthritis and inflammationand came up with a treatment for
it, well, that would extend myhealthy, comfortable life and it
might extend my life as well tosome extent, to the extent that
(46:51):
inflammation is a source ofaging and death, and
inflammation in fact is a majorcause of aging.
So I think the hope for agingresearch is to keep people
healthy as they age.
Now the problem always is thatif you do that, will you also be
(47:14):
prolonging their lives?
Because if you're keeping themhealthy, there's no reason for
them to suddenly drop dead, andso that's always an issue.
I don't think anyone has solvedthe problem of keeping lifespan
fixed, but keeping the healthypart, extending the healthy part
Usually both of them getextended.
(47:35):
So the part that you live in,with all the aches and pains and
diseases of all age, thatfraction hasn't actually changed
, and so I think that is aserious dilemma or a paradox in
the field.
Peter Bowes (47:52):
So you say you're 71 years old.
What do you feel that you'velearned from your research into
this book in terms of humanlongevity that you apply to
yourself?
Has anything changed in yourviewpoint?
Venki Ramakrishnan (48:07):
No, because a number of things that, well,
the age old advises, you know,eat in moderation.
I think who was it who's Iquote the person, but I've
forgotten his name who said youknow, eat moderately and mostly
plants.
You know, I think, eat food nottoo much and mostly plants?
(48:31):
Okay, michael Pollan, who wrotea book called In Defense of
Food Right, and what he wastalking about was real food as
opposed to food with lots ofadditives or highly processed
food and so on.
And so his thing was Eat food,meaning real food, not too much
(48:51):
and mostly plants, and I thinkthat's very good advice and that
actually takes into account,you know, not too many calories.
You know restricting yourcalories, eating a variety of
food to have a healthy diet, andso on.
And I think you know I'vealways led an active life.
I bicycle every day to work fivemiles a day.
(49:12):
If I get time.
I go to the gym two or threetimes a week to do weights and
some more cardio and sleep.
Now, I should work on sleep.
I'm actually terrible at it andmy wife always complains
because I'm on my what you callit, my stupid devices, you know,
(49:33):
on my phone or iPad orsomething you know, while I'm
trying to go to sleep, and thoseare really not at all good.
You know, and I think sleep isvery much underappreciated.
There's a brilliant book calledwhy we Sleep by Matthew Walker.
You know who's a sleep expert,and it's amazing.
(49:53):
We think of sleep as somethingyou know, because we have eyes
and we shut our eyes when wesleep.
But actually all sorts ofanimals, from very simple
organisms, actually sleep in thesense of going through a daily
rhythm of inactive periods andactive periods, and sleep is
highly conserved and you wouldthink we would not have evolved
(50:16):
it because when we're asleepwe're more at risk to predate,
predators and so on.
And so you know, it serves avery deep evolutionary purpose
and we're only now uncoveringall of the things that go on
when we sleep, includingrepairing damage that happens
during the day, and it's thatkind of damage that means that
(50:40):
sleep has an anti-aging benefit.
So you know, getting your beautysleep, people say you know it
actually turns out to be true.
So I think those three thingsare sort of key, and what the
book does is it talks about whythey're true.
What is the biological basisthat these age-old advice?
(51:03):
This age-old advice is true?
And I think in my life I havedone that.
Now my father is actually arecord holder.
He's 98 years old in our family98,.
Until 92, he was walking eightto 10 miles a day and he still
(51:23):
does his own laundry and cookingand he can't walk by himself
anymore because he's unsteady,but he'll go for a walk with me
or with my sister.
So I think you know that'sanother sort of thing, having
that, you know, balance in yourlife.
You know it sounds very tritebut it actually does work and I
(51:47):
don't think there's any realanti-aging medication or
supplement that works as well asthese things.
You know.
Peter Bowes (51:56):
Yeah, I'm totally on the same page as you.
I often say it comes down to Iput sleep at number one because
I think if you and like you Istruggle sometimes to get enough
sleep, but if you don't sleepwell, you're less inclined to
eat well the next day, or inother words, more inclined to
cheat and less inclined toexercise, because you don't feel
(52:17):
as if you have the energy.
Venki Ramakrishnan (52:19):
Yeah, it has lots of knock-on effects.
Yeah, I mean I would.
I might agree with you thatit's actually one of the most
beneficial things we can do, andour society is not geared to
encourage it.
You know even our sort of dailysort of schedule and you know
the hours we keep.
It's just simply not designedto encourage it, and I think we
(52:42):
need to think about that.
Peter Bowes (52:44):
Well, let me ask you in closing.
You say you're 71 years old.
You're talking to me from youroffice.
How do you feel about, as itapplies to the aging process,
how do you feel about retirement?
Venki Ramakrishnan (52:56):
Oh, I have a whole section on retirement in
my last chapter and so I'mretiring at the end of next year
, okay, and you know, I couldargue that I actually could have
retired even a few years ago,and I honestly don't think it
really made a huge difference toscience.
(53:17):
We're still doing good work,but there are lots of people who
are doing very good work in myarea and so I do feel that
people there's a balance.
You know you can't kick outpeople arbitrarily if they're
doing well and people age atdifferent rates.
So I think a fixed retirementage is not a good thing, because
(53:41):
we're biologically age atdifferent rates.
The other thing I should pointout is that different
professions will have differentrequirements.
I mean, if you're doing hardphysical labor or even if you're
doing, you know you're atrucker or some, you know a
mechanic having to work all daylong, or somebody who's on their
(54:03):
feet all day, you know cookingin a restaurant, you can't
expect them to keep going, youknow, beyond retirement age and
they wouldn't want to either.
And a curious thing in my owninstitute is all the scientists
want to hang on for as long asthey can, but all the people who
(54:24):
are doing the sort of more,what you would call the utility,
the people who do theconstruction in the building,
the electricians, plumbers,cleaners, even the IT people
they all want to retire as soonas they can, you know, as soon
as they're eligible.
So there is a difference.
And forcing everybody to worklonger is not a good thing.
(54:47):
And I also think that scientistsand you know people in
leadership positions hanging onforever is a very bad thing.
There's a generationintergenerational fairness issue
.
They're preventing youngerpeople, you know, from assuming
that.
And yet there's also a bigimbalance of power.
(55:07):
You can see in the US, you knowyou have Biden and Trump.
You know two relatively oldpeople, you know, probably going
to duke it out for the election.
You have guys like RupertMurdoch in their 90s, even
though he stepped down.
You know he controls a lot ofthe world's media.
It's just a huge imbalance ofpower.
And at the same time, we're alsomost creative when we're young.
(55:30):
That's not necessarily due tobiological age, although I think
we do decline cognitively, evenfrom our 20s, you know we
decline cognitively.
But creativity is also aboutfreshness.
When we're young, we're seeingeverything for the first time,
we're approaching everythingwith fresh eyes, and that's why
scientists, even writers, arevery creative when they're young
(55:53):
.
So I think, on the whole, Iwould be for, you know,
appropriate retirement.
I'm not for people hanging onforever, as some of my American
colleagues, you know.
They hang on until their 80sbecause they're having fun.
Well, they're having fun, butreally all the creative work is
(56:14):
being done by young people andtheir team, you know, it's not
they who are really driving it,you know.
So I think we need to thinkabout retirement as well as an
issue.
I'm with you on that.
Peter Bowes (56:27):
I think it's a fascinating issue and it's very
obvious to me as well thatcertainly one rule doesn't apply
to everyone when it comes toretirement.
And also, I don't suspect thatyou might officially be retiring
at the end of next year, but Ithink you will continue with
your thinking, your writing, andyou know whether you describe
that as work or not it is justyou and some of us, I think just
(56:51):
want to continue doing what wedo.
Venki Ramakrishnan (56:53):
Yeah, that's quite true.
But what I won't be doing istaking up resources, you know
funding etc.
Which would be better spent onyounger scientists.
You know people say half my agewere just starting out.
Peter Bowes (57:08):
Well, Venki, this has been a really fascinating
conversation.
I thoroughly enjoyed your book.
I would recommend it to anyone.
I appreciate your time.
Thank you very much indeed.
Thank you, thank you.
And Venki's book is why we Die,the New Science of Aging and
the Quest for Immortality.
There's a link to it in theshow notes for this episode,
(57:29):
along with the transcript ofthis conversation.
This has been a HealthSpanMedia production.
We'll be back soon with anotherepisode.
Thanks so much for listening.
I don't think anyone has solved the
problem of keeping lifespanfixed, but keeping the healthy
part, extending the healthy part.
Usually both of them getextended.
So the part that you live inwith you know all the aches and
pains and diseases of all days,that fraction hasn't actually
changed, and so I think that isa serious dilemma or paradox in
(00:30):
the field.
Peter Bowes (00:30):
Why we die.
The new science of ageing andthe quest for immortality is a
fascinating new book by thephysicist and molecular
biologist and Nobel laureate,Venki Ramakrishnan.
Hello again, welcome to theLive Long and Master Aging
podcast.
My name's Peter Bowes.
This is where we explore thescience and stories behind human
(00:52):
longevity.
Born in India, VenkiRamakrishnan has enjoyed a
distinguished career.
A former president of the RoyalSociety in London, he shared
the Nobel Prize in Chemistry in2009 for the work he and others
did, uncovering the structureand function of tiny cellular
particles called ribosomes.
(01:13):
Over the years, his careerinterests have shifted in
emphasis from theoreticalphysics to trying to understand
how our bodies work at amolecular level and the process
we call ageing.
Why we die addresses thatquestion, but also explores why
we live, why some of us enjoylonger lives than others, and
(01:35):
whether some of the more recentefforts to extend lifespan live
up to the hype.
Venki, welcome to the Live Longand Master Ageing podcast.
Hello, pleased to be here.
Yes, it's really good to talkto you and we will dive into the
subject of your book, but Iwould like first of all to do a
little romp through your career,and that's a phrase I get from
(01:57):
your book, which you describe asa romp through recent molecular
biology.
But let's just start by talkingabout you and your extremely
long and varied career.
You grew up in India.
Venki Ramakrishnan (02:09):
Yes, I grew up in India, except for about a
year and a half that I spent inAdelaide, australia, when I was
eight and nine, and then I leftIndia at the age of 19 to get a
PhD in physics in Ohio, in theUS, and in Ohio is also.
(02:29):
I like to joke that the onlynotable thing I accomplished in
my graduate school in physicswas that I met and married my
wife.
But because it turned out thatI really wasn't so thrilled
about the problem I was workingon, and even during my graduate
(02:50):
work, I became very interestedin molecular biology, and so I
know you introduced me as aphysicist, but no physicist with
assault or her assault wouldconsider me one, because I left
right after graduate school andnever did any work in it.
And the reason was that I usedto read articles in molecular
(03:12):
biology and realized, you know,molecular biology was undergoing
this huge revolution.
You know DNA, the structure ofDNA had been done in the early
50s and based on that we hadthis huge explosion in molecular
biology.
We were learning about thestructures of molecules, of cell
(03:33):
membranes, and how the immunesystem worked, how the nervous
system, you know, wasconstructed and so on.
So I thought, well, this was agood move.
But I didn't know any biology.
So I went to graduate schoolall over again at the University
of California in San Diego, inLa Jolla, california, and I had
(03:56):
the option of getting a secondPhD.
But after two years I realizedI'd learned enough biology.
I had acquired a background inbiology and I knew how to do lab
work, and so, based on anotherarticle I read, I went to Yale
University as a postdoctoralfellow to work on the ribosome,
(04:19):
which is this enormous complex?
They're tiny by everydaystandards, but they're really
enormous in that they have abouthalf a million atoms and
they're the machines thattranslate our genetic
information into the proteinsthat those genes code for.
So all the thousands ofproteins in ourselves that
(04:42):
actually make life, actually doits thing are made by the
ribosome using geneticinformation.
So every gene codes for aparticular protein, and so that
got me into the ribosome.
And then, throughout most of mycareer, I've worked on one or
(05:03):
other aspect of the ribosome andeventually we and others ended
up solving the atomic structureof the entire ribosome, and that
allowed us to figure out how itactually worked.
So of course it's an ongoingprocess and we're still working
on the ribosome.
(05:24):
Now the aging thing came aboutfor two reasons.
One is the ribosome is verycentral and you can think of all
the proteins in our cell, thethousands of proteins in our
cell.
Each one is doing its part andthey all have to work together
and proteins have to be made inthe right amount and they have
(05:45):
to be made at the right time.
If they're no longer needed,they have to be degraded.
So you think of it as acomplicated orchestra and
there's a lot of things in thecell which control when the
ribosome starts making proteins.
It checks the quality of theproteins made by the ribosome.
(06:06):
There are all kinds of checksand balances.
If the wrong thing is made orif it's defective, the cell has
ways of getting rid of it and itturns out this process breaks
down during aging and one of thechapters in my book it's called
Recycling the Garbage and it'sabout a field called
proteostasis which is aboutprotein turnover and quality
(06:31):
control.
It's very, very central to myfield of how the ribosome does
its thing.
So I had this peripheralinterest, even though I myself
don't work on aging.
The other is that as amolecular biologist I became
alarmed by the increasing amountof hype in the aging field and
(06:51):
I think a lot of it is driven bymoney.
You know there's lots ofprivate money.
A lot of billionaires areworried about aging and dying
and they're investing heavily inaging research and this is
distorting the field and leadingto wild claims.
There's also a lot of money inaging.
As people get older they'reworried about getting old and
(07:15):
dying.
They want to sort of postponeit and stay healthy.
So they're susceptible to allsorts of things.
People that people want to sellthem.
So I think I thought I'm closeenough to the field but not in
it, so I don't come with anyparticular biases and at the
(07:40):
same time I can actually readthe primary literature and so on
.
So I thought I would distillwhat is going on and try to give
the reader a sense of you know,what are the things that make
us age and what, if anything,can we do about them.
And finally, in my last coupleof chapters they're a bit
philosophical about what wouldbe the implications if we just
(08:03):
prolonged life and so on.
So that, in a nutshell, is sortof what got me into the book
and what the book is about.
Peter Bowes (08:10):
Yeah, and that's really interesting.
And I'm also wondering if theaging process, as it is
affecting you as an individual,like it affects all of us, has
also helped focus your mind.
Yes, you've got yourtheoretical, you've got your
scientific background and, asyou say, you are able to dive
into this subject in a certainamount of depth.
(08:30):
And I'm thinking also from apurely personal perspective.
Venki Ramakrishnan (08:35):
Oh yeah, I say in the beginning of the book
that you know one thing thatwould perhaps well let me back
off a bit.
There are lots and lots ofbooks about aging, and they fall
into many categories, you know.
So a number of books are abouthow to age gracefully and how to
accept the end.
You know things like that.
(08:56):
So that's one sort of category.
Another is you know about, youknow how to stay healthy, you
know exercising and doing thingsthat help, and you know those
are sort of self-help books.
Then there are books about, youknow, the biology of aging, and
these also fall into a coupleof categories, you know
(09:17):
somewhere.
Written by journalists, you know, and some of them have done a
good job, but they're not sortof equipped to be very critical
about the literature or reallydigest it and see what its
limitations are, and so theyoften rely on interviews and
(09:38):
chats with people you know toget a feel for what's going on.
And of course, those peoplethey talk to may have their own
biases.
And then some of them arewritten by scientists.
But these scientists often havesome vested interests, they
have companies, they haveanti-aging companies, and so
they're pushing a particularpoint of view, you know, and
(10:02):
often I would say, they'resomewhat biased towards their
own.
You know, whatever it is thatthey're sort of stunning.
So I say in the book at thebeginning that you know one
thing you can say about me is Idon't have any skin in the game.
I'm not I'm neither directly anaging researcher, so I don't
(10:22):
have preconceived biases.
And you know scientists also,once they have you know certain
theories and stuff that they'vepublished, they're reluctant to
back off.
You know from them.
You know they become sort ofvested in their own beliefs as
well.
And but the other is I don'thave any financial interest in
(10:42):
aging.
So I said I have no skin in thegame.
But then I point out of coursethat's not true for the reason
you mentioned, which is we allhave skin in the game because
we're all worried about agingand dying.
So in that sense you know, likeeverybody I have, I'm concerned
about it.
Peter Bowes (11:00):
And the fact that, as you say, some scientists have
and not all scientists.
Some scientists in this fieldare very pure, if you want to
use that word, but some do havevested interest and of course
that only adds to the to thelayperson, and I like to think
that this podcast is aimed atabsolutely everyone.
I try to not use the acronymsand boil everything to a level
(11:21):
that we can all benefit from.
But yeah, there are so manyvested interests.
It just adds to the confusionof people who are genuinely
interested in their agingprocess and their longevity but
then think, well, whichdirection do I go in?
Do I go down this veryspecialist diet route, or do I
adopt this kind of exercise, ordo I need a certain exactly?
Venki Ramakrishnan (11:42):
there's so many things being pushed, and so
what I've tried, you know, justto give you an illustration, in
the last 10 years alonethere've been over 300,000
papers published on aging okay,primary paper now, nobody could
read any of them.
You know all of those becauseyou know, just to read a
scientific paper, even if youwant to just read through it
(12:04):
without really thinking about it, takes at least a couple of
hours, you know, and probablylonger if you really want to
digest it.
So of course, I've had to behighly selective, and so what
I've tried to do is ask, youknow, what are the key advances
and and what are the key factorsinvolved in aging.
(12:25):
And I've tried to construct inmy book, you know, to try to go
from the very simple.
So I start at the molecularlevel.
So start with, for example, dna, you know, which contains
information that really, youknow run is responsible for the
program, the program of life,the program to sell.
(12:47):
And so I start with DNA, then Italk about how DNA can be
modified, then I talk aboutthings that affect DNA, then I
talk about what DNA makesproteins and how these proteins
interact and how the proteinshave to be recycled and how, if
proteins clump together, you getdiseases or aging like
Alzheimer's.
You know so.
And then I talk about thingsinside cells, like large
(13:10):
organelles, like mitochondria,which really it's amazing when
you and I try to also give a lotof history, how we found out
about this.
You know characters who youknow, some of them really weird
characters who made bigdiscoveries, and so the
hopefully the reader will go onthis voyage and by the end come
(13:35):
out with some broadunderstanding of the whole sort
of broad background of biologyof aging.
And the idea is that next timethey see a report on some huge
advance in aging according tothe headline, they'll be able to
judge, because they can relateit back to the biology that they
(13:59):
picked up from this book andthey can tell is this a real
advance or have there beenothers like this before which
have sort of fizzled out, or isthis just one more thing or is
it incremental?
You know they'll have a muchbetter sense of how to navigate
this.
You know constant, constant.
Peter Bowes (14:18):
You know drumbeat of, you know aging advances and
what was interesting to me is,essentially, this is a book
about living.
It's about living as well as wecan within the constraints of,
let's say, an average lifetime.
It's not about eternal life,it's not being immortal, it's
not living forever.
(14:38):
It's about living, but youactually start by analyzing
death and what it is to die.
Venki Ramakrishnan (14:44):
I'm just curious as to why you took that
approach yeah, because you know,if you want to talk about dying
and aging, you have to actuallyask what do you mean by death?
You know, and what do you meanby aging?
And just to give you a verytrivial example, when you die,
you know you have over atrillion cells in your body.
(15:05):
Most of them are still alive atthe moment of your death.
That's the amazing thing, youknow so.
So what do you mean?
You're dead, you know all thosecells are still alive.
In fact, after you die,somebody could take your heart
or your kidney and and donate itto some recipient who needs it
right, and people have done that, you know.
(15:25):
People go and liver transplants, kidney transplants, heart
transplants, etc.
So you know what do we meanwhen we die?
Well, what it means is that wedie as an individual.
An individual is somebody whofunctions as a unit.
So the collection of the cellsthat make you function as an
(15:48):
individual, that collection, isno longer working as a coherent
whole, and so that's when youdie.
And typically nowadays, mostplaces define death by brain
death.
Okay, in the old days, you know, if your heart stopped, you
were considered dead, but thenpeople figured out how to
(16:08):
resuscitate you, you know withCPR and so on, and so they felt,
oh, that's not a gooddefinition.
So then it went to brain deathand even brain death.
You know, the exact details areslightly different and I point
out in the book that those caseswhere, especially in the United
States, the definition of deathin one state is not the same as
in another state and there wasa very famous case of a young
(16:31):
woman who died and I think inCalifornia, she declared death
but her family she was not deadby the standards of New Jersey
and so her family, you know,appealed and got her body
transferred to New Jersey andkept her alive by New Jersey
standards.
And then, you know, eventuallyshe died and you know, she was
(16:53):
in a coma.
And I think you know it justgoes to show you that defining
death is not not trivial andit's also, I point out, at the
other end, defining, you know,when a person's life begins.
It's also quite complicated,you know, is it at the moment of
conception, is it at the momentof implantation?
(17:15):
Is it when the embryo reaches acertain stage?
You know, is it when the fetusis viable?
I mean, these are notnecessarily scientific questions
, they're, you know, social andcultural questions as well, and
that's why we have this.
You know, big polarizationabout abortion.
Peter Bowes (17:33):
It's about arguing about when life begins, you know
and you write about compressedmorbidity which as an expression
, as a, as a phrase, I think iscrucially important.
Venki Ramakrishnan (17:45):
If you understand and get what it means
and I look to just explain yourunderstanding very interesting
concept, and so the idea ofcompression or morbidity is that
you live healthily for nearlyall your life and the period
(18:05):
when you're sort of sufferingdebilitation and decrepitude of
old age is very, very short.
So that period of morbidity iscompressed to a very short
period.
And so the idea is you stayhealthy all your life and then
suddenly, you know, collapseokay, within a very short time.
(18:26):
And the person you know whofirst coined the phrase freeze,
he said that look, this is alittle bit like the one horse
shea.
He quotes a poem by OliverWendell Holmes, from the thing
from the 19th century.
A shea is like a is a one ortwo horse carry, one or two
(18:47):
person carriage.
And he said, the one horse sheain the poem is constructed so
that all its parts wear out atabout the same time.
So nothing ever, it's neverdefective, you know, because all
the parts are going along atthe same time.
And this farmer is riding along, and one day he's riding along
(19:08):
and suddenly he finds himself onthe ground in a heap of dust
because the entire carriage isdisintegrated in front of him,
right under him.
Now that would be the equivalentof compression of morbidity,
because it has a paradox whichis if you're healthy, why would
you suddenly die?
You know all your organs arehealthy, you're feeling great,
(19:30):
well, why would you die?
And the reality is that almosteverything that has helped us
stay healthy for example,statins for cholesterol or blood
pressure medication to preventhigh blood pressure, or, you
know, diabetes drugs, you knowmetformin and things like that
(19:50):
All those things that havehelped us against diseases of
old age and helped us stayhealthy they have all
effectively prolonged our lives.
So the period that we areactually, you know, suffering
from the disabilities of old agehas not changed as a fraction
(20:12):
of our lives.
So, in fact, because we'reliving longer, you could argue
that we're actually spendingmore years, you know, with all
these aches and pains anddisabilities of old age, and you
can see that.
You know nursing homes and carehomes for older people.
It's a booming business, youknow, because more and more
(20:32):
people are going into them andthey're going, you know, living
longer.
So my I say in the book,compression of morbidity is a
very worthy goal, but it's notclear yet how we can achieve it.
Okay, because you know what wemay do is simply prolong life
and at the end, everything's notnecessarily going to break down
(20:55):
at the same time and, you know,as things start breaking down,
well, then you have yourmorbidity, okay, and so it's a
complicated problem.
The one thing that suggeststhat there's some hope for it
comes from studies ofcentenarians.
So I communicated with TomPearls, who's a world leader in
(21:16):
this area, and he has hisstudies show that people who
live especially 105 or 110 theseare what are called super
centenarians.
You know even centenarians ofpeople who live to be a hundred.
So, but these semi and semi,super and super centenarians,
(21:38):
they turn out to have very shortperiods when they're actually
sort of ill or, you know, frail,and they they often tend to
have almost none of the diseasesthat many people have as they
get older.
So they're very healthy formost of their lives and have a
very short period of sort ofwhat I call illnesses of old age
(22:01):
.
So that suggests that maybe,you know, if we can find out why
these people have somehowmanaged to live healthily for a
very long time and then, youknow, suddenly die, that would
be something that would be worthlooking into.
Peter Bowes (22:21):
And I think, just to emphasize the point, the best
example I can think of ofsomeone achieving a compressed
morbidity in modern times wasQueen Elizabeth.
She died, yes exactly she wasworking right to the very end.
Venki Ramakrishnan (22:37):
Yeah, and actually you know her husband,
prince Philip, was also veryhealthy until you know, just the
last few years of his life.
So perhaps you know peopleshould sequence their genomes
and see in their lifestyle.
Of course you know, you have torealize they also had the very
(22:57):
best environment and medicalcare and so on so it's perhaps
not a very fair comparison, but,on the other hand, it does say
something about, and they didn'tlive past a hundred.
Neither of them live past ahundred, so they're not, in a
sense, the most extreme of thecases, but it's a good point.
Peter Bowes (23:18):
And I think it's also interesting just non-famous
people that I have known ofwho've got to a great age.
What's interesting to me isthat they often achieve that,
most times achieve that withoutthinking about it, they just get
to a great age and they livetheir lives.
But then you, sometimes you diveinto the way that they've lived
their lives, whether it's beingtheir diet, their exercise
(23:39):
regime or, in many cases, theirsocial connections, their social
circles and the people thatthey've had around them at a
great age.
I think these are all thethings that play into that
ability to live long and to livewell.
Venki Ramakrishnan (23:53):
Yeah, so I point out in my book that Tom
Pearls has a website calledliving to 100.com and you can
fill out all sorts of thingsabout yourself and your habits
and you know your health history, and it'll tell you, you know,
how long you can expect to live.
And I do fairly well, becauseone of the things apparently is
(24:16):
if you have a parent who livedvery long, like in their 90s,
that somehow improves yourchances for genetic reasons
alone.
I have a father who's 98 yearsold.
He's well, he's going to turn98 this Saturday and he's still
going strong.
He, he does his own laundry andis cooking and until a few
(24:38):
years ago he would go off, youknow, on long walks and shopping
and so on.
And he still walks, you know, acouple of miles.
So you know, I don't knowexactly what it is about him,
except I think he has a zest forlife.
I think maybe you know that'squite important, but of course a
(25:00):
lot of it is due to somecombination of genetics and diet
and habits and so on.
Peter Bowes (25:07):
I think that factor that you mentioned of people
that do their own gardening andlaundry and household chores
until they achieve a as they'reachieving a great age, is
important.
I mean you could characterizeit as movement.
It doesn't really matter asmuch as you do.
Yes, absolutely.
Venki Ramakrishnan (25:23):
And using your brain.
I mean when you're cooking ordoing, you know somewhat
complicated tasks.
You know it's more active thanyou know if you're simply
passively receiving.
You know watching television orsomething, and you know.
So of course this is allanecdotal, but I think you know
these people who studycentenarians, like Tom Pearls.
(25:44):
They're looking systematicallyat you, know what are their
habits, what are their healthhistories, and then they're also
going to sequence their genomesand also sequence their you
know, methylation methylonesbecause DNA methylation is a
modification of DNA that'ssomehow related to aging, and
(26:07):
they could see other methylationpatterns, these tags on their
DNA as they age, but they'redifferent from people who don't
live as long.
So there's a lot of informationto be gained and we'll learn
more about that as these studiesprogress.
Peter Bowes (26:25):
You cover in the book, caloric restriction, which
I think, if you look at thescience, there's perhaps some of
the most solid science behindthe idea that a certain amount
of caloric restriction, reducingthe amount of calories that you
consume on a daily basis couldhelp you live longer and better.
And the dilemma, of course, fora lot of people here is that
(26:48):
many people prefer quality oflife, and quality of life does
not involve caloric restrictionover quantity.
Ultimately, the number of yearsI point out, you know.
Venki Ramakrishnan (26:59):
So the evidence for caloric restriction
is quite good, which is caloricrestriction is when you give an
animal or a person just enoughcalories and nutrients so
they're not malnourished.
So just enough and no more.
And that in studies on manydifferent species, all the way
(27:24):
from worms and flies to mammals,has shown to improve lifespan
compared to an ad-limitum dietwhere they're fed as much as
they want.
You know the food they can eatas much as they want.
But some critics have pointedout it's not a fair comparison
because an ad-limitum diet isbasically unnatural.
(27:47):
You know, the idea is we neverhad an ad-limitum diet until
modern times when food becameplentiful.
And so they say well, you couldjust as well conclude that an
ad-limitum diet is really badfor you, you know.
And that if you don't, you know, if you restrict your calories
(28:08):
it's better, but it doesn't haveto be so extremely restricted.
And there are also studies onintermittent fasting.
You know people say if you fastfor 16 hours at a time or eat
only in a five-hour window, thatthat can, you know, that can
help, and that too has beencontested.
(28:28):
So I point out, in the book,for many of these claims there
are also counterclaims, and weneed to be a little cautious
about how good it is.
However, there's no questionthat, at least compared to an
ad-limitum diet, which is eatinga lot and eating as much as you
want, a calorically restricteddiet does better.
(28:49):
And so the question is then why?
And this has led to thediscovery of these
nutrient-sensing pathways.
Well, actually I'm saying thatwrong, because the
nutrient-sensing pathways didn'tall come out of aging research.
Only one of them did, but theother one was a complete
accident, which is the Torpathway.
(29:11):
And it turns out that thispathway senses nutrients, and if
nutrients are plentiful, itdoes one thing it turns on
protein synthesis and it shutsdown degradation and recycling
of proteins.
On the other hand, if nutrientsare reduced, and even if very
(29:32):
specific nutrients are reduced,so you may get a lot of calories
, but you're missing certainamino acids, that too can have
an effect.
And what it does is it shutsdown what I call initiation, the
beginning of protein synthesis,so it prevents the ribosome,
which is my molecule, fromstarting to make proteins, and
(29:55):
so you stop making more proteinsand at the same time, you turn
on these pathways which areinvolved in removing what I call
the garbage garbage recyclersof the cell, these things called
phagosomes, which take thingsto the lysosome, which is an
organelle which is like a giantrecycling center where things
(30:17):
are broken down and recycled.
So there's lots of things toconnect the biology with these
broad studies, observationalstudies like what does diet do
to your health?
And that's another fascinatingthing how we're able to connect
the underlying molecular biologyand the detailed physiology of
(30:42):
the cell to broad things likediet.
Peter Bowes (30:46):
And I think what it is valuable to look into and to
analyze is that some of theseinterventions whether it's a
calorically restricted diet orsomething else that may
emphasize may impact yourlongevity, the number of years
that you live, and it also hasan impact on how you live now,
which could well influence howyou live in years to come.
(31:09):
But I think for a lot of people, living now is crucially
important and just by speakingpersonally as an element of
caloric restriction makes mefeel actually good, makes me
feel better, makes me feel alittle bit lighter, makes me
feel more energized, and I thinkthat could potentially help me
live longer.
Venki Ramakrishnan (31:28):
Yeah, so the fact is that these animals on
calorically restricted dietsthey're not lethargic, they're
actually quite active.
I think you're frozen, I'm notsure.
Are you hearing me?
Peter Bowes (31:43):
So I had indeed frozen the internet letters down
.
So we're actually picking upthis conversation 24 hours later
, internet restored.
Thank you for sticking with us.
So, let me just return to thepoint that you were Actually
just making.
We were talking about calorierestriction and the impact on
(32:03):
especially laboratory animals.
When we look at mice, thosecalorie restricted mice are not
lethargic, they're veryenergetic.
And you see it, don't you inthe mouse wheel in terms of how
they, and it's the same.
Venki Ramakrishnan (32:15):
It's the same with worms.
You know, when these firstmutants, these aging mutants,
were discovered in worms Again,the worms were.
You know Cynthia Kenyon calledthem frisky.
You know they were movingaround and they behaved a lot
like younger worms, so it wasn'tas if they were kind of living
longer, but sort of in adoddering state.
(32:37):
And so there is something aboutit also being fairly healthy.
I wouldn't say caloricrestriction comes with no
effects.
You know people under extremecaloric restriction that is a
very rigorous kind, which justenough to keep you alive and not
(33:01):
malnourished they do havethings they feel cold, they have
loss of libido, they're slowerto heal wounds, typical things
like that.
So it's not entirely, I wouldsay, without cost.
And the most important thing isvery hard psychologically to
(33:23):
keep it up.
And that is, if you take micethat have been caloricly
restricted and they're doingfine, you would think they'd be
happy doing fine, but as soon asyou allow them to eat as much
as they want, they gorge away.
So there's something about ourevolution we didn't grow up in a
(33:47):
time of plentiful food, so wesomehow want to put away that
food.
And so I think there is aquestion of how viable is this
as a strategy?
There is also the question ofpeople are always comparing
(34:08):
caloric restriction diets orthese intermittent fasting diets
with a sort of more liberal,almost all-you-can-eat diet.
Certainly, with animals it's anall-you-can-eat diet.
Now it could be that all youcan eat is one extreme and
that's not great for you, but itcould also be that maybe eating
(34:29):
in moderation and eatinghealthy food, balanced food, is
perhaps almost as good.
I don't know if anybody hasdone that comparison.
The one comparison is withstudies on chimpanzees.
There was a group at NIH and agroup at Wisconsin.
The Wisconsin group definitelyfelt that the restricted
(34:52):
chimpanzees were better off, theNIH group not so much, and the
main difference was that thecontrol diet of the Wisconsin
monkeys was much richer, and sothe control animals there did
develop all the symptoms ofoverindulgence.
(35:14):
I forget all the details, butthey did have many of what we
call diseases of excess and notso much in the NIH group.
And that suggests there may bea happy medium and moderation
(35:35):
and not overindulging isprobably and having a healthy
diet.
Peter Bowes (35:42):
Moderation is always the word that I come back
to when I'm discussing this,and to some people it might be a
boring word.
Moderation doesn't soundexciting like intermittent
fasting or no, but it'ssomething we can live with.
Well, yes, exactly Something wecan live with.
Exactly, and I think the pointis that, yes, there are lots of
fasting regimes.
(36:02):
Some may be difficult tosustain long term.
There is some evidence that acertain amount of caloric
restriction could be beneficialfor us.
But if you look at, if youapply this to humans and you
look at the way most people,especially in the Western world,
eat these days, if you look atthe extremes, the fast food,
look at television advertising,billboard advertising of food,
(36:26):
that is the excess extreme.
Which points to me.
It shows to me that, yes, thereis a happy medium, there's a
moderation, and the challengeseems to be to persuade people
that moderation which isn'textreme is potentially very good
for us.
Venki Ramakrishnan (36:43):
Yeah, and also I feel moderation is much
more sustainable than having anextreme calorically restricted
diet, which would be much harderto follow.
I mean even and I thinkmoderation also carries fewer
risks of some of the downsidesof a highly restricted diet.
Peter Bowes (37:04):
Let me just change direction a little bit.
The whole principle ofevolution is or at least one of
the principles is survival ofthe fittest.
Evolving over many, many years,it's the survival of the
fittest principle that governsthe way that we evolve.
So I'm curious why evolutionhasn't created a human being
(37:25):
that evolves to live longer andstay healthy for longer.
Venki Ramakrishnan (37:30):
Right, but that's because we think of
fittest as the fitness of theindividual.
But you know, fitness is, inevolutionary terms, is defined
more as being successful atpassing on your genes, and so
every species has to have thisbalance.
They have to have a balancebetween being able to procreate
(37:53):
successfully, producing enoughoffspring that their genes live
on in their offspring, versusliving longer.
And at some point there's no.
If you've succeeded in livinglong enough to pass on your
genes, evolution doesn't carehow long you as an individual
(38:16):
live, because the genes survive,and that's what's selected for.
Of course, genes, you know youselect for the Genes are what
are selected for.
But of course genes don't existin a vacuum.
They exist in individuals.
So the individual has tosurvive and be successful enough
at procreating, and this isperhaps why different species
(38:38):
have very different lifespans.
So I'll give you a broad ruleof thumb among mammals the
larger the mammal is, the longerlived it is on average.
They're outliers and I discussthem in the book because the
outliers are actually veryinteresting.
We could learn from them.
In fact, humans are an outlier.
We live much longer than wouldbe expected for someone, our
(39:03):
species, our size.
But you take mice.
Mice live for about two years.
Now why don't mice live for 300years, you know, like a whale
or a shark or something?
And it's because there's noadvantage to a mice, because
mice would get eaten or starvedlong before that.
So there's no advantage forevolution to allow mice to
(39:28):
evolve, mice to live very longor to age more slowly, because
they'd die of external causesthat have nothing to do with
aging, like predators.
And so smaller animals alsohave a higher metabolism and in
fact it's metabolism that's morecorrelated with age.
So faster than metabolism, theshorter the life.
(39:51):
So I think my chapter is calledLive Fast and Die Young, or
something like that.
And so evolution is, for eachspecies, optimized fitness.
So if you have a chance to livevery long, then your metabolism
is slower, then you take longerto procreate.
(40:14):
There's an advantage to livinglonger If you're a short animal,
fast metabolic rate, fastgrowth, very quickly get to
puberty and procreation.
There's no particular advantagein terms of evolution in having
that species live longer.
Now there's a curious thing Ipoint out in the book about bats
(40:36):
.
So bats are about the same size, or even some of them are even
smaller than mice, and yet theylive.
You know, a bat has lived for40 years.
I mean, that's an amazingrecord for such a small animal,
and that too has an evolutionarybasis.
So bats can fly, so they'remore easily able to escape
(40:59):
predators, and it turns out thatanimals that can fly are
generally longer lived thancomparably sized animals that
are terrestrially bound, andthat again makes perfect
evolutionary sense.
Peter Bowes (41:15):
So in human terms and we kind of touched on this
at the beginning of theinterview there are those in the
longevity industry, if we cancall it that, that aspire to
live to a very great age,whether it's 120, 180, or even
much, much longer than that, andthere are some that believe
that within our lifetime.
(41:36):
So let's say in the next coupleof decades that the science is
going to evolve so quickly thatit is going to make that
dramatic life extension possible.
Venki Ramakrishnan (41:46):
What do you think?
Well, I don't think anybody canknow.
If you were to ask me myopinion, I would side on the.
I would come on the side ofpeople like Jay Olshansky and
others who believe that Ourcurrent lifespan is pretty much
fixed and to overcome it willtake much longer.
(42:09):
Okay, it'll take some realbreakthroughs in aging research,
and part of the problem isaging is not one thing.
I doubt that there's going to bea magic bullet which will say
if we do this, we're going tosolve aging, and I think aging
is highly complex.
There are multiple, almostparallel strands that go into
(42:34):
aging, and it's going to takesome time to sort of pick
through all those strands andcome up with a real solution to
aging more slowly, Even in ourindividual selves, our organs
age at different rates, asjudged by various biomarkers and
(42:56):
so on.
So the idea that there'll beone magic bullet and that'll
solve aging, I don't buy it, andso it's really a question of
opinion, I admit.
My opinion is that it's goingto take a while, and long before
that happens, we need a numberof other advances to be made.
(43:19):
Now, of course, the moreoptimistic people will say well,
look at the rate at whichknowledge is exploding and we'll
have AI and genomics and we'llfigure out all this stuff.
I don't buy it, but I can't sayas a scientist, I can't say
they're absolutely wrong.
Okay, that is not.
(43:40):
I mean, there are a number ofcharlatans in the business, but
this is not a charlatan-likequestion.
This is a real question onwhich I think serious people
could disagree.
Now one serious scientist,Stephen Ostad, actually made the
bet with Ostansky about whethera person who lived to be 150
(44:05):
years has been born already ornot.
And they made a bet and I thinkthe bet was $150 or something
which they calculated wouldbecome $1 million in 150 years,
although I don't know what $1million would be worth then with
inflation.
But anyway, I think they don'tdisagree about the fundamental
(44:28):
biology.
I think they disagree aboutwhether these advances will come
in time for someone born now,before they reach current life
expectancy, and I think thereare others who believe that
there's a constant race.
So we start aging, but scienceadvances and by the time they
(44:53):
get really old, we'll be able toextend their lives another 10
or 20 years and then, by thetime that goes by, we'll be able
to extend it again another 10or 20 years, and that's how
they'll do that.
And the extreme view of this isthat we could live a few
hundred years already because ofadvances.
I think those people are, tosay politely, blind optimists.
(45:17):
But that's, as I say, a matterof opinion.
Peter Bowes (45:24):
Yeah, and I think, and would you agree, that
perhaps some of thoseserious-minded researchers who
genuinely believe that we mayhave extreme life extension at
some stage and are doing goodwork in that area, that at least
some of their work mightactually help us now and might
benefit us in the next decade ofour lives?
Venki Ramakrishnan (45:47):
I think the really big advantage to aging
research is that it will helpwith what I call the
disabilities or the decrepitudeof old age.
We have inflammation.
I'm 71.
I'm saying only because it'stoday.
(46:08):
A generation ago I'd be readyto die, and so I'm 71.
I have been fairly active mostof my life, and now I have joint
pain in my shoulder and kneebecause of osteoarthritis Clear
disease of inflammation in aging, and I even describe it in the
(46:28):
book.
And so if somebody were to lookat what causes this
osteoarthritis and inflammationand came up with a treatment for
it, well, that would extend myhealthy, comfortable life and it
might extend my life as well tosome extent, to the extent that
(46:51):
inflammation is a source ofaging and death, and
inflammation in fact is a majorcause of aging.
So I think the hope for agingresearch is to keep people
healthy as they age.
Now the problem always is thatif you do that, will you also be
(47:14):
prolonging their lives?
Because if you're keeping themhealthy, there's no reason for
them to suddenly drop dead, andso that's always an issue.
I don't think anyone has solvedthe problem of keeping lifespan
fixed, but keeping the healthypart, extending the healthy part
Usually both of them getextended.
(47:35):
So the part that you live in,with all the aches and pains and
diseases of all age, thatfraction hasn't actually changed
, and so I think that is aserious dilemma or a paradox in
the field.
Peter Bowes (47:52):
So you say you're 71 years old.
What do you feel that you'velearned from your research into
this book in terms of humanlongevity that you apply to
yourself?
Has anything changed in yourviewpoint?
Venki Ramakrishnan (48:07):
No, because a number of things that, well,
the age old advises, you know,eat in moderation.
I think who was it who's Iquote the person, but I've
forgotten his name who said youknow, eat moderately and mostly
plants.
You know, I think, eat food nottoo much and mostly plants?
(48:31):
Okay, michael Pollan, who wrotea book called In Defense of
Food Right, and what he wastalking about was real food as
opposed to food with lots ofadditives or highly processed
food and so on.
And so his thing was Eat food,meaning real food, not too much
(48:51):
and mostly plants, and I thinkthat's very good advice and that
actually takes into account,you know, not too many calories.
You know restricting yourcalories, eating a variety of
food to have a healthy diet, andso on.
And I think you know I'vealways led an active life.
I bicycle every day to work fivemiles a day.
(49:12):
If I get time.
I go to the gym two or threetimes a week to do weights and
some more cardio and sleep.
Now, I should work on sleep.
I'm actually terrible at it andmy wife always complains
because I'm on my what you callit, my stupid devices, you know,
(49:33):
on my phone or iPad orsomething you know, while I'm
trying to go to sleep, and thoseare really not at all good.
You know, and I think sleep isvery much underappreciated.
There's a brilliant book calledwhy we Sleep by Matthew Walker.
You know who's a sleep expert,and it's amazing.
(49:53):
We think of sleep as somethingyou know, because we have eyes
and we shut our eyes when wesleep.
But actually all sorts ofanimals, from very simple
organisms, actually sleep in thesense of going through a daily
rhythm of inactive periods andactive periods, and sleep is
highly conserved and you wouldthink we would not have evolved
(50:16):
it because when we're asleepwe're more at risk to predate,
predators and so on.
And so you know, it serves avery deep evolutionary purpose
and we're only now uncoveringall of the things that go on
when we sleep, includingrepairing damage that happens
during the day, and it's thatkind of damage that means that
(50:40):
sleep has an anti-aging benefit.
So you know, getting your beautysleep, people say you know it
actually turns out to be true.
So I think those three thingsare sort of key, and what the
book does is it talks about whythey're true.
What is the biological basisthat these age-old advice?
(51:03):
This age-old advice is true?
And I think in my life I havedone that.
Now my father is actually arecord holder.
He's 98 years old in our family98,.
Until 92, he was walking eightto 10 miles a day and he still
(51:23):
does his own laundry and cookingand he can't walk by himself
anymore because he's unsteady,but he'll go for a walk with me
or with my sister.
So I think you know that'sanother sort of thing, having
that, you know, balance in yourlife.
You know it sounds very tritebut it actually does work and I
(51:47):
don't think there's any realanti-aging medication or
supplement that works as well asthese things.
You know.
Peter Bowes (51:56):
Yeah, I'm totally on the same page as you.
I often say it comes down to Iput sleep at number one because
I think if you and like you Istruggle sometimes to get enough
sleep, but if you don't sleepwell, you're less inclined to
eat well the next day, or inother words, more inclined to
cheat and less inclined toexercise, because you don't feel
(52:17):
as if you have the energy.
Venki Ramakrishnan (52:19):
Yeah, it has lots of knock-on effects.
Yeah, I mean I would.
I might agree with you thatit's actually one of the most
beneficial things we can do, andour society is not geared to
encourage it.
You know even our sort of dailysort of schedule and you know
the hours we keep.
It's just simply not designedto encourage it, and I think we
(52:42):
need to think about that.
Peter Bowes (52:44):
Well, let me ask you in closing.
You say you're 71 years old.
You're talking to me from youroffice.
How do you feel about, as itapplies to the aging process,
how do you feel about retirement?
Venki Ramakrishnan (52:56):
Oh, I have a whole section on retirement in
my last chapter and so I'mretiring at the end of next year
, okay, and you know, I couldargue that I actually could have
retired even a few years ago,and I honestly don't think it
really made a huge difference toscience.
(53:17):
We're still doing good work,but there are lots of people who
are doing very good work in myarea and so I do feel that
people there's a balance.
You know you can't kick outpeople arbitrarily if they're
doing well and people age atdifferent rates.
So I think a fixed retirementage is not a good thing, because
(53:41):
we're biologically age atdifferent rates.
The other thing I should pointout is that different
professions will have differentrequirements.
I mean, if you're doing hardphysical labor or even if you're
doing, you know you're atrucker or some, you know a
mechanic having to work all daylong, or somebody who's on their
(54:03):
feet all day, you know cookingin a restaurant, you can't
expect them to keep going, youknow, beyond retirement age and
they wouldn't want to either.
And a curious thing in my owninstitute is all the scientists
want to hang on for as long asthey can, but all the people who
(54:24):
are doing the sort of more,what you would call the utility,
the people who do theconstruction in the building,
the electricians, plumbers,cleaners, even the IT people
they all want to retire as soonas they can, you know, as soon
as they're eligible.
So there is a difference.
And forcing everybody to worklonger is not a good thing.
(54:47):
And I also think that scientistsand you know people in
leadership positions hanging onforever is a very bad thing.
There's a generationintergenerational fairness issue
.
They're preventing youngerpeople, you know, from assuming
that.
And yet there's also a bigimbalance of power.
(55:07):
You can see in the US, you knowyou have Biden and Trump.
You know two relatively oldpeople, you know, probably going
to duke it out for the election.
You have guys like RupertMurdoch in their 90s, even
though he stepped down.
You know he controls a lot ofthe world's media.
It's just a huge imbalance ofpower.
And at the same time, we're alsomost creative when we're young.
(55:30):
That's not necessarily due tobiological age, although I think
we do decline cognitively, evenfrom our 20s, you know we
decline cognitively.
But creativity is also aboutfreshness.
When we're young, we're seeingeverything for the first time,
we're approaching everythingwith fresh eyes, and that's why
scientists, even writers, arevery creative when they're young
(55:53):
.
So I think, on the whole, Iwould be for, you know,
appropriate retirement.
I'm not for people hanging onforever, as some of my American
colleagues, you know.
They hang on until their 80sbecause they're having fun.
Well, they're having fun, butreally all the creative work is
(56:14):
being done by young people andtheir team, you know, it's not
they who are really driving it,you know.
So I think we need to thinkabout retirement as well as an
issue.
I'm with you on that.
Peter Bowes (56:27):
I think it's a fascinating issue and it's very
obvious to me as well thatcertainly one rule doesn't apply
to everyone when it comes toretirement.
And also, I don't suspect thatyou might officially be retiring
at the end of next year, but Ithink you will continue with
your thinking, your writing, andyou know whether you describe
that as work or not it is justyou and some of us, I think just
(56:51):
want to continue doing what wedo.
Venki Ramakrishnan (56:53):
Yeah, that's quite true.
But what I won't be doing istaking up resources, you know
funding etc.
Which would be better spent onyounger scientists.
You know people say half my agewere just starting out.
Peter Bowes (57:08):
Well, Venki, this has been a really fascinating
conversation.
I thoroughly enjoyed your book.
I would recommend it to anyone.
I appreciate your time.
Thank you very much indeed.
Thank you, thank you.
And Venki's book is why we Die,the New Science of Aging and
the Quest for Immortality.
There's a link to it in theshow notes for this episode,
(57:29):
along with the transcript ofthis conversation.
This has been a HealthSpanMedia production.
We'll be back soon with anotherepisode.
Thanks so much for listening.
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