Episode Transcript
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Coleen T. Murphy (00:00):
We already
have a sort of tenuous
relationship with the public.
That is scientists.
Right, many of us are trying todo the very best that we can
and try to make sure that whatwe say is not outlandish and
it's actually realistic and thatour research, when we describe
it, it doesn't like go waybeyond what we can actually
achieve, because when someonepromises you something and they
(00:21):
don't come through, theyshouldn't have faith in you.
So that you know this promisingof things that are never going
to happen really destroys thepublic's faith in scientists.
Peter Bowes (00:32):
Coleen T Murphy is
a professor of genomics and
molecular biology at PrincetonUniversity and the author of how
we Age the Science of Longevity.
Hello again, welcome to theLive, long and Master Aging
podcast.
My ame is Peter Bowes.
This is where we explore thescience and stories behind human
(00:54):
longevity, so you can see whyProfessor Murphy's book appealed
to me.
It is indeed a deep dive into avast amount of research
conducted over recent decades totry to better understand this
thing called aging.
Coleen Murphy, welcome to theLive, long and Master Aging
podcast.
Coleen T. Murphy (01:14):
Thank you for
having me, peter.
Peter Bowes (01:15):
So it is a deep
dive and you approach many of
the fundamental questions aboutaging.
I would like to start withperhaps what I consider to be
the most of fundamental ofquestions, and that is what is
aging?
I know there are lots ofdifferent definitions from
researchers and scientists, butwhat is your view on what aging
(01:36):
is?
Coleen T. Murphy (01:38):
Right?
That's a really hard questionto answer, depending on the
level that you're interested in.
So, you know, we study themolecular and cellular levels of
aging, but in a general sense,aging is what happens when we
can no longer carry out therepair mechanisms that keep us
young.
So we can think of all theenergy our body uses, a lot of
(02:00):
that is used to repair, likerepair all the damage in
ourselves and our DNA, and atsome point those repair
mechanisms stop working as well,and then the end result is, as
we've all noticed, changes inour skin, our metabolism, our
connective tissues, right, sothings that then ultimately
(02:21):
result in us feeling older and,you know, experiencing aging.
Peter Bowes (02:26):
Well, we're gonna
dive a little bit more deeply
into that.
Maybe first of all, I could askyou this is a vast subject area
what got you interested in thefirst place?
What piqued your interest inaging that made this your
lifelong interest and career?
Coleen T. Murphy (02:42):
I think it's a
really interesting question.
You know I'm a scientist.
I'm interested in what are some,you know, fascinating questions
that we could use science toanswer, and as a graduate
student I became really welltrained in studying biochemistry
and at the time I was reallybecame an expert in studying one
(03:03):
particular protein and theprotein it interacted with, and,
as you can imagine, that's notreally a fun topic for everyone
to talk about.
I was fascinated with it, but noone else was, and so at some
point I realized that there aresome really big questions, and
aging is one of those where youcould get interested from, you
know, an epidemiological,evolutionary point of view, all
(03:25):
kinds of different levelssociological, economic but it's
also something that we couldaddress scientifically, and I
realized that that would be agreat place to spend my time and
energy is trying to understandnot just what causes aging and
what aging really is, but arethere ways that we could slow it
down, and so that's how I gotinterested.
(03:47):
It's kind of a big idea thatonce I finished my PhD, I could
really apply my my efforts toand has your attitude towards it
as a subject evolved over theyears?
Peter Bowes (03:59):
I know, from a
non-scientific community
perspective, a lot of peoplebegin to think about aging and
their own lifespan or healthspan as I often prefer to talk
about but the passing of theyears they notice that in
midlife, in maybe their 40s and50s, because things start
changing.
It might be gray hair, it mightbe their parents suffering some
(04:19):
ill health or the death oftheir grandparents.
There are life changes thataffect us all that for some it's
a sort of a light bulb, isn'tit that yes, we're all getting
old and we're going to have todeal with it.
Coleen T. Murphy (04:30):
And I'm almost
feeling the opposite now that
it's becoming a reality.
I kind of want to move intosomething else, to study but
I've been interested in since Iwas, you know, in my mid 30s and
early 30s, and so, in fact, oneof the questions I addressed
very early on when I started myown lab was, instead of just
looking at what happens late inlife, really understanding that
(04:52):
aging starts in midlife.
And one of the things that wouldpersonally affect me is that,
even if I could take a drug thatwould allow me to live to be
150, I would still at that point, need it to have kids all by a
certain age, and so reproductiveaging was one of the really big
areas that I felt was neglected.
At the time that was around 2005, 2006.
(05:14):
And it's interesting because inthe past, now, 15 years later,
20 years later, there's a realeffort to try to understand that
, and I'm really gratified thatsome other people have picked up
that idea that aging starts inmidlife and one of the earliest
consequences of reproductiveaging.
But then, of course,immediately after that, start
(05:34):
thinking about well, you know,my knees fall apart things like
that, but the most importantthing, I think, for all of us is
maintaining our cognitivefunction, and so that's the
other big area that my lab isinterested in, because we really
want to maintain our cognitivefunction as long as we can,
regardless of like.
Maybe our bodies won't be thebest, but at least if our brains
can work, that would give us abetter quality of life.
Peter Bowes (05:55):
The reproductive
side of aging, which you
mentioned, is really interestingbecause I guess, from an
evolutionary perspective, oncewe have achieved reproduction,
that we have produced offspring,there isn't really much reason
to keep on living, from a bigpicture evolution perspective,
that we have done what we wereperhaps even created for and
(06:18):
that is to produce offspring tocontinue our gene pool.
Is that a fair way to look atit?
Coleen T. Murphy (06:24):
It is
especially when we start
thinking about why do thingsbreak down?
Why do organisms stop puttingeffort into those repair
mechanisms?
And if we really look at the,you know in CL against this, you
know the tiny nematode that wework with, which has a lot of
parallels with our own bodiesand how we age, I started
thinking of aging as theopposite kind of really.
(06:44):
These animals are programmed toreplace themselves, to
reproduce, and then once thatjob is done, then everything
after that is kind of gravy.
And so instead of thinkingabout, like looking for a mutant
that extends lifespan, weshould be looking for things
that extend how long they canreproduce, because that actually
has the underlying feature,because their bodies have to
stay healthy at the same time inorder to do that well, and so
(07:07):
it actually ends up extendinglifespan as almost a.
It's like a secondary function,it's like just a fringe benefit
.
It's not really the main point,and that's true, for you know
mammals as well.
You know the idea of thegrandmother hypothesis is very
attractive, the idea that thereason that we live so long is
so that we can contribute to thefitness of our grand progeny,
(07:29):
and there seems to be somesupport for that.
But even C elegans has a muchlonger lifespan than its
reproductive span.
So that's why I'm saying likelifespan is actually kind of
like a you know, it's just extra, like that extra bit after it.
So that's the part, but that'sthe part we really, really want
to extend.
So it's important for us tounderstand what limits that.
Why does it stop repairingitself?
(07:51):
And how can we make thosemechanisms last you know well
past, when they normally should?
Peter Bowes (07:56):
The idea of living
long to look after children, or
even grandchildren, to benefittheir lives is interesting to me
, because I often ask people whyare you interested in this?
Why do you want to live to agreat age?
And almost always, the firstreason is because of my children
.
I want to be with my children,I want to enjoy life with my
children, and part and parcel ofthat, of course, is doing
(08:19):
things that will help them livegood lives as well, and it's
interesting that people will saythat without really thinking
about it, maybe understandingsome of the science that you're
alluding to, but it does seem tocome.
It's almost an instinct topeople that they want to
continue on this earth becauseof their children.
Coleen T. Murphy (08:35):
That's right.
It's a very natural thing towant to do and also to limit the
burden that we put on ourchildren as we grow old.
Right, if we can stay healthyas long as possible, that will.
That's another way of helpingour children.
Peter Bowes (08:47):
So in the book
you've told you've alluded to
this already in terms of thewear and tear that contributes
to aging you draw the analogywith an old car, and this is
often used that we've all hadold cars in our lives and we see
the wear and tear and theultimate death of that vehicle.
And we also know that if wemaintain that vehicle and change
(09:08):
the oil regularly in the olddays or before electric cars,
that the car will probablysurvive longer.
That is quite a good analogy,isn't it, with the human body.
Coleen T. Murphy (09:17):
Yeah, it's a
little bit cliched in the aging
field, but it really is a goodanalogy because you really put
in the effort to you know thatenergy expenditure to repair
things is exactly what our cellsare doing as much as possible,
and even to the point where youknow you replace parts right, so
we have cells that replacethemselves over time.
So I really do like thatanalogy.
(09:39):
It's really good.
And, as I mentioned in the book, you know I did have the
opportunity to go to Cuba onceand you could see these old like
these cars from the.
They were from the 40s and theyhad been like continually
maintained and replaced and sothey definitely weren't even the
same.
They probably maybe just eventhe shell of the car was the
same, but like the effort thathad been gone into maintaining
(10:00):
them is very much analogous towhat we're trying to do with our
own cells.
Peter Bowes (10:05):
So, once we have a
good understanding of what aging
is and why we age and some ofthe processes involved, why do
we need to?
To further our understanding ofaging, in other words, do what
a lot of people in your fieldare doing, and that is to try to
find interventions that help usto live longer, and certainly
(10:27):
longer and healthier.
That seems to be fairly obvious, but what is the impetus to
really dig deep into this, totry to extend health span?
Coleen T. Murphy (10:36):
Well, one of
the main things that's been
pointed out by many people inthe field is that we have all
these different age-relateddiseases, and really they're all
important to study.
But if their root cause is allshared, then it makes sense to
study that shared component,right?
So studying aging itself, theidea is, could we slow that down
?
And even if we don't livelonger?
(10:57):
Jim Fries had this idea ofcompression of morbidity, so
that means that you don't changethe life span of somebody, but
you make them healthier so thatthey don't spend a long time
suffering, and then maybe youhad the same lifetime, but only
the very end.
You compress the time whenpeople are sick, and I think for
most people that resonates.
(11:17):
They may not care to live, tobe to 100 or 150 or whatever,
but they do want to spend theyears that they're on this earth
as being as healthy as possible, and so that's really the goal
of much of the aging field.
Peter Bowes (11:29):
And the example I
give, at least in recent months,
of that of someone who reallyachieved that the Queen of
England, queen Elizabeth.
She lived to a great agemid-90s and, as we all know, she
was working until just a fewdays before her death.
That is a classic example,isn't it?
Coleen T. Murphy (11:44):
That's right.
So people who can be reallyfunctional, healthy, right up
into the variant.
I think that's probably thebest model of how we want to
maintain function with age.
Peter Bowes (11:53):
Where do you stand
on some of the lingo, some of
the language that is used in thelongevity field, and you're
actually quite blunt about youropinions in your book.
Look things like reversingaging, anti-aging, which, from
my perspective, I'm pro-aging,I'm pro-healthy aging because I
just see it quite simply assomething that's chronological.
(12:14):
I'm a day older than I wasyesterday, my next birthday,
I'll be year older, and so itgoes on.
The goal for me is to age, butage in a healthy way.
Coleen T. Murphy (12:24):
That's right.
I think more.
I don't want people to thinkthat our field is promising them
something that we may not beable to achieve.
I think it's good you knowwe're trying to understand.
Are there interventions that wecan use?
We can basically start, youknow, giving to people that
would help them slow aging.
(12:44):
I think it's just wrong topromise things that are just not
realistic, and the reason istwofold One, just because nobody
should lie to people andsecondly, because you know we
already have a sort of tenuousrelationship with the public
that is scientists.
Right, we, many of us, aretrying to do the very best that
we can and try to make sure thatwhat we say is not outlandish
(13:07):
and it's actually realistic andthat our research, when we
describe it, it doesn't like goway beyond what we're trying,
what we can actually achieve.
Because when someone promisesyou something and they don't
come through, they shouldn'thave faith in you.
And so that you know, thispromising of things that are
never going to happen reallydestroys the public's faith in
(13:30):
scientists.
And you know, especially in theUnited States with all the, the
NIH is funding most of ourresearch and so and taxpayers
pay that, and I want the publicto know that we are doing our
best and we're not lying aboutwhat we can achieve.
So I just, yeah, I want peopleto be hear the truth and not
like some promise that I don'tthink we can fulfill it and
(13:51):
doesn't mean that we don't careabout it and then we're not
working our hardest to do theright thing.
Peter Bowes (13:55):
So what comes to
mind is this phrase we often
hear longevity escape velocity.
Now maybe you can explain whatthat that means, but essentially
it's talking about the, thespeed of advances.
That could actually be atipping point in terms of aging,
and to me a lot of it does seemunrealistic and overly
(14:17):
ambitious.
Coleen T. Murphy (14:18):
Yeah, I think
part of it is that we people
don't like incremental advances.
They want to have like a magicpill that takes care of
everything, instead ofrecognizing that a lot of the
breakthroughs in many fields aregoing to give them a tool and
another tool and another toolthat's going to help address
problems.
For an example, you know, we wedon't call statins a longevity
(14:42):
drug, right, but they arehelping people live longer, so
it's increasing our lifeexpectancy.
I think that we'll have to seewhat happens with the GLP
peptides agonist, but if thosereally do help people lose
weight and maintain weight andimprove their cardiovascular
function, in the end that shouldalso help people improve their,
(15:04):
their lifespan right andhealthy lifespan.
And so I think the problem ispeople are looking for a drug
that doesn't do anything else.
It only extends lifespan.
But in fact, if we think about alot of these medical advances,
they are getting us there,they're trying, they're actually
attacking some of the rootcauses, especially the metabolic
causes of our aging, and couldbe really helpful for a lot of
people.
Now there's also, I thinkthere's this idea of taking a
(15:30):
person who's extremely healthyalready and making them live, I
guess, forever, and so that'sdifferent from this idea of
slowing down aging and reducingage related diseases, and I
think I think actually the thelatter is more important, right,
like helping everybody livelonger and getting reaching
their maximum potential andtheir healthiest lifespan.
(15:52):
I think that is actually reallyimportant, and it's not so
important to find you know aperson who's gonna live 500
years.
It's just to me they'redifferent priorities.
Peter Bowes (16:01):
And the suggestion
sometimes that the first person
to live to, I don't know, athousand years old perhaps has
already been born, these quitewild sounding statements that
you occasionally hear in termsof predictions of potential
longevity.
Is there any kind of sciencethat would back up such claims?
Coleen T. Murphy (16:21):
I mean,
ironically, the only thing that
would support any of that wouldbe something like our examples
in C elegans, right, when wehave mutants that can live 10
times as long.
But you know, I think the wayto think of all the things that
we find in C elegans, where wehave a mutant that very it's
very healthy and lives twice orthree times as long, when you
scale that up to mammals, thatgives you like a 30% boost,
(16:42):
right?
So I I mean we'll never know,right, you and I will not be on
this earth to find out theanswer to this question, but my
guess is no, but it's justsomething exciting to say.
But again, that erodes theconfidence in some of the erodes
the confidence in scientistswho are doing the actual science
to move the field forward.
Peter Bowes (17:00):
Well, let's talk
about that and maybe leave some
of these potentially negativeconnotations aside.
Yes, and I was going to ask andyou've already in part answered
this question, but I was goingto ask in and I suspect perhaps
it's the most frequent questionthat you hear and that is based
on your decades of research whatare the interventions that
(17:20):
could very realistically help usjust live a little bit longer
and extend health span, thenumber of years that we enjoy
optimum health without havingthose chronic diseases?
And to come to mind to me isusually, while you optimize your
exercise, you have a balanceddiet and we can debate forever
what the best balanced diet isand you get enough sleep.
(17:42):
Sleep, exercise and food cometop of the list, and then the
interventions, the kind ofthings, perhaps, that you're
researching.
Coleen T. Murphy (17:49):
Peter, I think
that's exactly the right order
of things, the rightprioritization.
So what you've just mentionedare the things that everyone can
do right now to live theirhealthiest and probably the
longest life.
Exercise, I think, is it'sprobably the strongest.
Actually, that one is mostconsistently very good and it's
(18:10):
one that probably people don'tappreciate enough.
But we have to recognize also,not everyone is in a position to
do a lot of exercise, right?
So if you're a shift worker, ifyou know, so it's really and
you didn't mention that theother way to live the longest
possible is to be rich, right,because you have the best chance
of doing things like buyinghealthy food and having free
time to exercise and havingpreventive health care.
(18:33):
So those are the kinds ofthings that we kind of, as you
know, when you have enough money, you just sort of take for
granted, but actually that'sreally what, the things that can
help everyone live longer.
So if we can make themuniformly apply.
So, yeah, those are the thingswe can do now.
There are several people, youknow, the scientific data all
(18:54):
supports the idea of dietaryrestriction in one form or
another.
But if you think about it,that's what we do to, you know,
like our insects and our animalsin a lab and we don't give them
a choice.
And in fact, actually, if yougive them a choice, they will
stop doing as soon as possible,which makes sense, right.
And so the idea that a lot ofpeople have, that everybody
should be dietary restriction tolive their longest life, I
(19:17):
think is both unrealistic andkind of unfair.
You know, there's veryinteresting statistics about who
chooses to do extra, especiallyextreme caloric restriction,
and I think that part of these,that my fascination with these
DLP peptides, is because I thinkit's getting at this root of a
question of like our brainsactually control hunger, and so
(19:40):
I think that those levels ofthese peptides are different in
everyone, and so some peopleprobably feel like they're not.
They feel hungry all the timeand other people don't, just
based on their chemistry, and soI think it's interesting to
look at who chooses to dietaryrestrict themselves and who
really can't, and there's, yeah,and it's not really a moral
judgment.
(20:00):
I think we have to get away fromthat.
I think there's like definitelychemistry in our brains and our
bodies that affects how we feeltowards food, and it's not that
easy to caloric restrict formost people, and so I think that
part of the reason it'simportant to understand the
science of caloric restrictionis because it's a very important
thing, and so I think that'swhy we're trying to understand
the science of caloricrestriction is so that we can
figure out okay, is theresomething we can do that would
mimic that state and help us behealthy but wouldn't cause us to
(20:22):
lose out on one of the greatestjoys in life is to, you know,
eat a good meal, right?
And so I think moving usforward scientifically will be
understanding all those pathways, so that we don't have to miss
out on things that are just likepart of having a high quality
life.
Peter Bowes (20:41):
And so I'm just
simply confused by the extremes
that they hear about.
So you might hear about certainpeople who will frequently go
without food or water, only dietfor several days, which is very
, very extreme.
At the least extreme you couldsay, well, maybe you're going to
calorie restrict by just nothaving a dessert on three days a
(21:01):
week.
That, for some people, islimiting calories by just
pairing back a little bit everyday, and so I think that's why
we can use the word moderation.
That could be one of the bestinterventions.
And the issue there, maybe thechallenge there from a societal
perspective, I wonder if youthink about this is education,
education to show people thatyou yes, you might be.
(21:23):
You can call it caloricrestriction.
Other people might just call itcutting back on a few meals or
just eating less, or having halfa plate instead of a full plate
a few times a week.
Coleen T. Murphy (21:35):
But again,
none of that is really like the
cutting edge of aging research,right.
It's just sort of what we kindof known for a long time.
That's why I'm actually a littlebored by all the dietary
restrictions and stuff otherthan trying to understand, like,
what are the mechanisms andwhat are the you know, the real
genetic components and how canwe manipulate those.
Because from a scientificperspective that's actually
really interesting, but from asocietal point, like all these
(21:59):
discussions about what we shouldand shouldn't eat and it
changes all the time too, right,if you notice like there's
these huge trends and so innutrition science and then when
you find out some of the backingfor that is always a little bit
disturbing.
So I want to stick to themolecules and the hope, as I
said, is, you know, I hope thatwe'll get to a point where we
(22:19):
can separate the idea of likeliving longer and then having to
like have a terrible life,because I, frankly, I really
think that a lot of the dietaryrestrictions have, like we do it
to C elegans, we see they havea better, like a longer lifespan
.
I just think that's not reallygreat way to live and so I'm not
focused on that particularthing.
(22:39):
I think there's a lot of other,more interesting ways to live
longer.
Peter Bowes (22:43):
Okay, well, let's
talk about them.
What do you think are the moreinteresting ways to live longer?
Yeah, well.
Coleen T. Murphy (22:48):
I, you know,
understand the genetics, right.
So we have this great modelsystem and really, you know,
when I got into the field, thepart of the reason was because I
had read about and then heardCynthia Kenning give her talk
about her lab's work, so that'swhere I did my postdoc at UCSF
and she had discovered there arethese mutant C elegans, so like
it has a change in a singlenucleotide and a single gene in
(23:13):
this worm and it lives twice aslong and it's super healthy,
right, it's not like on itsdeathbed for a long time.
It really stretches out thehealthy part of lifespan.
And we've found that thoseworms actually maintain their
oocytes longer, so they have alonger reproductive span, and we
know the mechanisms now whythat happens.
And they maintain their neuronslonger, so they can.
We figured out how to dolearning and memory assays in
(23:34):
these animals so they actuallymaintain their cognitive
function longer, and so thoseare.
And so understanding how thoseanimals do that and
undercovering all the geneticsgives us new, possibly
pharmaceutical targets, right,because then we can say, okay, I
see that those long lived, youknow, long remembering worms
turn up this protein.
What if I found a drug thatcould do the same thing, right.
(23:57):
So that would be great.
And so that's why it's reallyimportant for us to do the.
Not just stop it all, like okay, well, just stop eating and
live longer.
That like instead, if we couldactually figure out, like, what
is the thing that we want to dobetter, and can we find a drug
that does that well and makesand not bad, that would be great
, right.
And so I think you know there'sa whole biotech industry that's
(24:17):
just trying to take off andthat's like you know.
The end of my book is mostlyabout that and how we're on the
verge.
I think there's really a lot ofexciting science has gone from
the lab to now these biotechstartups and other things that
were just on the verge of it.
So that's what I kind of wantthe audience to know is that
we're not going to, we're notgoing to.
We shouldn't say, oh, we foundout everything, we're done, we
(24:41):
know everything about longevity.
We actually are learning a lot,but now we're on a stage where
those things are beingtranslated, I think, into
possible interventions, and thatis really exciting.
And so what I hope the readersget out of this is some
information about what thoseinterventions might be like
what's the molecular basis forit, and I'm sort of getting you
know what to look for.
(25:02):
Who might, who might actuallycrack this?
That's really exciting to me.
Peter Bowes (25:06):
And just remind, as
you mentioned, C elegans, this
little tiny nematode wormsseveral times which are used,
have been used for a long timeextensively in this area of
research.
Why are they such a good model?
Coleen T. Murphy (25:18):
Okay.
So these I should haveintroduced them better myself.
So you know, they're tinylittle animal, they only they
look like a like.
If you held up the plate ofthem, they look like lint.
So they're, they're transparent.
We look through them, can seethem on microscope.
The reason they're so great isbecause we can manipulate every
single one of them, but we can.
(25:39):
They live for only three weeksand while during that time, if
you looked at them under themicroscope, anyone would be able
to tell me oh, that one lookslike a young one and this one
looks old, because they actuallythey start to get wrinkled and
fat and they start start moving.
Well, right, so they really arereminiscent of the kind of
aging changes that we see.
And, like I said, this mutant,the insulin receptor mutant,
(25:59):
daf2, that Cynthia Kenyon firstidentified, that lives twice as
long and it's super healthy anddoes everything.
So that is a great, you know,it's a great tool, and so people
have also done great studies,for example in Drosophila.
So those two animals, the seaelegans and.
Drosophila yeah, the fruit fly.
Those have given us so muchinformation about how to live
(26:24):
longer and better lives and Ithink that's underappreciated in
general because, like often,people skip straight to the
mammalian studies, the mousestudies and things, which is
important.
Right, we take our stuff inworms and we go look at what
happens in a mouse before wemove on, but it's really easy to
find important things in thesemodel systems and so that's why
we're so excited about it and Iwant people to know that that's
(26:45):
how much of the aging field.
Many of the genes that we studythey are really well
characterizing those animals.
Peter Bowes (26:52):
Yeah, and I think
it's important to explain that,
because a lot of people willdismiss longevity science when
they discover that it is, asthey might put it, only animals,
or we're all animals.
But it was done in rodents orfruit flies or tiny worms, and
that, as you've explained, thereis a process here, that that's
where it starts and clearly,especially with drug
interventions, that hasultimately to be human trials.
Coleen T. Murphy (27:15):
That's right,
and so the other thing you can
do in these small systems isfigure out what's safe.
You know, if we did a drugscreen, for example, in sea
elegans, we found out that somedrug that we're really
interested in for the brainended up killing all of them.
We would never move forwardwith them, right?
So it's, it's just such an easy, easy tool to use, but so
(27:37):
powerful because you can do somuch so fast.
So we hope that by the time weget to the point of doing a
collaboration with, like ourcolleagues who work with mice,
that we'll have done somethingthat where we really understand
it because it's also veryexpensive to do these studies
and in higher organisms, and sowe don't want to waste a lot of
time and money on animalsstudying something that's not
(27:58):
important.
So that's, you know, these,these invertebrate systems, are
fantastic for all of thosereasons.
Peter Bowes (28:05):
And once we get to
the point where there are more
and more nutraceutical,pharmaceutical interventions
based on decades of solidscience and we see, as I say,
more and more of them on themarket, then comes the dilemma
for people, doesn't it of well,what's best for me and how can I
choose the best intervention?
Yes, based on science, it isgoing to help me achieve a
(28:27):
greater, healthier age, and thatis, I mean, that's already a
reality now, isn't it for somany people in terms of how to
pass apart all the science andfigure out what is the most
positive for them?
Coleen T. Murphy (28:40):
That's
absolutely, and in fact it's
made a little bit morecomplicated because we also have
to take it face value.
So, say, you order somenutraceutical, you have to take
it face value what's going to bein that bottle?
Because right nownutraceuticals are treated
differently from drugs and theFDA is not going through the
process of approving them.
And so one of the really greatefforts that's happening right
(29:03):
now is being organized by NeeraBartzellay at Einstein is this
TAME trial.
So that's a trial.
We've known that metformin isbeneficial for years and years,
right, and so this is an exampletrial of trying to figure out
whether, if you did a largeclinical trial, could you
actually say this drug should behelpful for longevity.
(29:24):
And they're doing that by avariety of metrics, right, like
health metrics, includinglooking at what changes in the
blood.
And the idea here is that ifyou since that's a pilot program
could you then convince the FDAthat we should be doing trials
to like check efficacy, right,and I think that's really
important to do, because rightnow you know you have to trust,
(29:48):
like what's being sold.
I think that's a little scary,and I was at a meeting in
September where someone hadtaken, like, just like various I
forget which drug it was andthey did mass spec on it, and
only one of the like eighth thatthey bought had the drug that
was supposed to be in it, and soI think that's a big concern.
So that's even separate frommaking the decision of what I
(30:10):
should take.
So, say you, you know what's inthe bottle was true, and the FDA
said it was like something youknow.
Also, companies are having tomake the hard choice of how do
you test something for efficacy,because they want to get
something that's real too, notjust because, you know, down the
line, it's important for thesecompanies to survive and make
good choices, and so several ofthem are doing smart things by
(30:33):
testing not for longevity butfor age related diseases, right,
and so that's pretty smart,because if you can, you know,
find a real disease that you cantrust track, then you can, you
know, subject that to an FDAtrial, and so I think those
kinds of approaches are reallyimportant for moving the field
from like this idea and nonutritional like, maybe it works
(30:54):
, maybe it doesn't.
It's something that's really atrusted drug that you could be
prescribed by your doctor.
Peter Bowes (31:00):
I think you've
highlighted a really important
issue and problem and tragically, suddenly we live in this
unscrupulous world these days,why you really Find it difficult
to believe anything, andespecially that you're reading
on the internet and the purityof these Compounds that people
are potentially buying is such asuch a vitally important issue
(31:21):
and people Can often be easilylead, I guess, when something is
being offered to them at acheaper price and they assume it
is the same thing as they'vebeen paying a little bit more
for, unlikely to go to cheaperroad and it may not be what they
think it is in that littlebottle that's right and you know
, and, of course, how.
Coleen T. Murphy (31:39):
And then you
also like get into the whole
psychosomatic thing of like issomething really like?
Are you just, you know, havingsome sort of placebo effect?
You're taking some?
So I think we have to have somereal metrics to be able to tell
a patient, yes, you're actually, you know, slowing down your
aging.
And there's some diagnosticsare getting there.
You know whether they're quitethere yet and not sure, but but
(32:00):
that's, you know, one of theefforts of the field as well as
to do things like these.
You know blood diagnosticclocks, like the I'm aging clock
kind of methylation DNA marks,and try to say, well, can we
actually Measure your aging rate, measure your age, and then how
that changes when you take anintervention?
Right, so I think once we getthose working really well, that
(32:20):
could be a very effective toolTo be able to help people assess
how fast they're aging andwhether the thing that they're
taking is actually doingsomething or not.
Peter Bowes (32:30):
Another area of
confusion, sometimes in terms of
biological aging, chronologicalaging, you're talking about
attempting to assess ourbiological Age, which in itself
is a complicated equation, andthere are lots of companies out
there with different metrics indifferent ways of calculating
that.
We need to, I think, settle ona way that is is broadly agreed
(32:52):
as as the way to determinesomeone's biological age.
Coleen T. Murphy (32:56):
Otherwise, you
just going to Puppet a more
confusion that's right and, likeI said, I think that there are
real efforts is, I don't youknow, the scientists are working
this.
You're not trying to pull afast one, actually really trying
to develop a clock, clock thatthey really do find reproducible
and accessible.
So, like I think that we'regoing to get there, because
there are a lot of efforts beingmade to that, to that, to
(33:18):
address that point.
Peter Bowes (33:20):
You.
We've talked a little bit aboutexercise and how crucially
important I think.
I will put exercise that numberone of my my list of things
that I need to achieve every day.
Will we and you address this inthe book?
Do you think we'll get to apoint where there is exercise in
a pill?
Coleen T. Murphy (33:36):
Well, I do
think we already have a few of
those drugs that do help boostmuscle function.
And again, you know, there's aperspective from people like you
and I who are, you know, prettyhealthy, sitting here.
There are people who are nevergoing to be able to exercise for
one reason or another, and sofinding drugs that could help
them as well that's actually oneof my favorite themes lately in
(33:57):
the aging field is this ideathat, okay, not worrying about
the guy who's just trying tolike maximize his life forever,
but instead focusing on peoplewho you know.
If you have some sort ofdegenerative muscle problem,
this might be helpful.
Or my favorite one recently islooking at there's the idea that
for Satellitic drugs, thismight help patients, so people
(34:21):
who had childhood cancers,because they have a lot of
problems come in life, and so ifsome of these anti aging kind
of therapeutics that we'redeveloping could help any people
In that situation, it would befantastic.
So I think we can't think ofall you know, longevity, aging
research as a fundamentallyselfish endeavor.
It actually could help a lotmore people than we are
initially realizing.
Peter Bowes (34:43):
And there's a lot
of really fascinating research
going on at the moment intomitochondrial health and,
essentially, the the energycenters of our bodies.
The payoff from good Strengththere is good physical strength,
good muscular strength.
That translates into perhapsnot falling down when you're
older that's right, preventsfrailty.
There's a long sequence ofbenefits there and I know you've
(35:05):
looked into this as well interms of the work that's going
on trying to understandmitochondria and how to boost
our mitochondrial health.
Coleen T. Murphy (35:10):
Yeah, it's
funny because in my own lab I
Sworn to never work onmitochondria and then at some
point I ended up studying andfigure it.
You know we were looking atreproductive aging and we
discovered that your life in aactually really helps them
maintain their oversight,function longer, because they're
their OSI turns out there.
(35:32):
Mitochondria, like basically,they're one of the main things
that fall apart and, yeah,mitochondria it's, it's
Undeniable, they're supercrucial and helping them
maintain function not only helpswith muscles, but it turns out
neurons as well.
And so, yeah, mitochondrialhealth is super important and
there are several drugs thatthat could be helpful with that
(35:54):
as well, and those are actuallybeing marketed as well.
Peter Bowes (35:57):
Let me ask you a
more personal question.
As you age and kind of touchedon this already our attitudes
change, or the ideas that we'vehad maybe Set aside for, for
newer ideas about aging and howwe as an individual want to
approach it, what we can do topursue our own healthy longevity
.
Have your attitudes in thatrespect changed as a result of
(36:20):
some of the research that you'vedone?
Coleen T. Murphy (36:23):
Awesome, my
research.
Peter Bowes (36:25):
Or maybe not your
research, maybe your life
experiences.
Coleen T. Murphy (36:28):
I don't know.
Like I said, I don't know as itbecomes real, I just kind of a
step away and start just focuson the curiosity driven problems
that no, I have, like almosttwo minds, like we, like in my
own lab, really really startedto focus almost exclusively on
maintaining cognitive function.
So doing drug screens for that,because I feel like this could
(36:50):
be a really good path forward,regardless of and there may be
even like Side effects that arebeneficial as well.
So, for example, we just had apaper with our collaborators,
all the data.
So a saws lab is Focus.
He's actually when people is onthe pair of biosis work, you
know the stitching of the twoanimals together and finding out
(37:10):
that there's factors in theblood they're sharing.
So that's what he was alreadyfamous for.
So we had discovered in Celegans there is a particular
protein that if we make more ofit and make it more active, just
in one neuron we can turn outin turn that on in one neuron of
old worms and it completelyrescues their memory.
(37:31):
Of course you're like, oh,that's nice, that's worms.
But then we convinced saw tohelp us, and he and Greg beer in
his lab they injected that samemutated version of the protein.
So worms and Mammals have theidentical protein and we made
they made same mutation andinjected into the hippocampus of
(37:53):
two year old mice.
So two year old mice are aboutSeventy, effectively like a
seventy five to eighty year oldperson, and these mice already
were experiencing some cognitivedecline.
So they injected into thebrains and then let them recover
and then subjected them to somebehavioral assays and what they
found was that these mice havegreat memory.
(38:15):
So just this one protein, justactivating it in the right place
, and old animals completelyrescued their memory and also
they started behaving in ayounger way, which I couldn't be
quantified and I can't explainhow that works.
So now we're really interestedin the idea of could we find a
drug that mimics that effect,right?
(38:36):
So that would be an example ofwhat we can do, that where we go
from worms to higher organisms,and so that's the part I'm
really interested in, because Ithink maintain cognitive
Functions probably my number onepriority as far as the aging
field goes.
Me personally, know, I love tobe able to get back to sprinting
, right, but that's like that'sa different thing altogether.
(38:58):
That probably doesn't haveanything to do with my lab
research.
Peter Bowes (39:01):
Right, just to
delve a little bit into that
research that you mentioned.
So how do you assess a mouse interms of its memory ability,
and is there a definition ofwhat a mouse is doing that shows
its behaving in a younger way?
Coleen T. Murphy (39:14):
Yeah, so for
the, for the first part, the
memory.
So that's actually really wellestablished field and lots of
other great neuroscientists haveworked on that for a long time.
In Sal's lab in particular,what they were using were two
different Test one called thenovel object recognition test.
That's when my son a cage, andyou put an object in it and let
them get used to it and then,like a day later, ignore that
(39:36):
one.
But if you put another objectin there, they'll pay more
attention to that new thing.
Okay, so that means that theyremember the old one and they
and so basically you can trackhow much time they spend with
that new object.
So that's one test.
And then there's the radio armwater maze.
So that's where you have aplatform where the mice can swim
to get out.
But they have to remember whenthat platform is, and so you can
(40:00):
, and they learn to do that overtime.
So in that same asset you canmeasure learning short term
memory and then long term memory, and you can measure the number
of errors that they make.
And so the you know the micewhere we put the protein in it.
Actually they made fewer errorsand they had much better long
term memory.
Okay, now, as far as the healthmetric, that was kind of cute
because I didn't know about thisbefore.
(40:21):
Saul called me and told me thathe observed this, and that was
that he was.
If you look at the mice intheir cages, apparently young
mice sort of make these nestsand they take care of them with
their bedding, and then, whenthey get old, you know, like all
of us, stop caring around ourenvironment, and they stop doing
that.
They stop caring about theirenvironment, stop making these
little nests.
And so you can have this nonparametric.
(40:43):
You can actually like look atthem and give them a score from
good to bad.
And the mice with this rescuedprotein actually it made their,
made them take care of theirnests again.
So I don't know the molecularmechanism behind that at all, it
was just an observation, but itwas a significant difference
and so that made me.
(41:04):
That made me very happy,because it also suggests that
this modification you madebecause you can go to age, right
, you can have something what isa flower for Algeron, right,
you like, you can have animprovement in your brain.
But then there's something elsethey would do negatively, right
, and that's Really what wedon't want to do, and so what we
want to do is something wherewe Maintain our brain, but also
(41:27):
you don't be nice to also havesome like health effect as well.
Peter Bowes (41:30):
That's positive
really interesting, fascinating.
Let me ask you in closing a bigpicture question, and that is
Is life in this world, thisearth that we live on, worth
living for a long time?
And I'm thinking of thosegeopolitical issues that we all
face, those climate issues thatwe're facing and they're posing
(41:52):
a real challenge to mankind atthe moment.
Is this going to be a worldthat we want to live in for a
long time?
Coleen T. Murphy (41:58):
and that's you
know, peter, that's the point I
make at the very end of my book.
I appreciate you bring it up.
We really need to keep in mindthat if we want to live so long,
there's better be an earth leftfor us to live on and all
possible ways right, like weneed to pay more attention to
our climate.
That's real.
There's real urgency there, andwe need to pay attention to
other human beings that we'reliving with on this earth, and
(42:20):
so if we don't do those twothings, then it doesn't matter
if we invent a pill tomorrow tolive 500 years, right.
So we really need to payattention to all those things
and not just focus on this Onearea.
So you know, as a scientist whodo what we can, but it's up to
all of us to try to make thisplace a world worth living in.
Peter Bowes (42:40):
Couldn't agree with
you more.
Coleen Murphy is fascinatingconversation.
We've just really skirtedaround the surface of the very
deep dive that you do in thisbook and, as I mentioned at the
beginning, looking back overdecades of really interesting
research.
Coleen T. Murphy (42:53):
Thank you very
much indeed and thank you for
having me here.
Peter Bowes (42:56):
My pleasure.
Coleen Murphy's book is how weage the science of longevity.
There's a link to it in theshow notes for this episode,
along with a transcript of thisconversation.
This has been a health spanmedia production.
We'll be back with anotherepisode very soon.
In the meantime, thank you somuch for listening.