1:03

Hello

1:12

everyone and welcome to Talk Nerdy. Today

1:15

is Monday, February 26th,

1:17

2024 and I'm the

1:19

host of the show, Dr. Cara Santa Maria. This

1:22

week we have a great episode coming up for

1:24

you, but before we dive into it, I do

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page. patrons, the ones who

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pledge the most per episode

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include Daniel Lang, David J.

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E. Smith, Mary Neva, Brian

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Thank you all so, so

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much. All right. So

2:18

let's get into it. This week, I

2:20

had the opportunity to chat with Dr.

2:23

Colleen T. Murphy. She

2:25

is a professor of genomics

2:27

and molecular biology at Princeton

2:29

University and also the director

2:32

of Princeton's Glenn Foundation for Research

2:34

on Aging and the director of

2:36

the Simon's Collaboration on Plasticity in

2:39

the Aging Brain. So she has

2:41

a new book out, which is all about

2:43

aging, titled appropriately How

2:45

We Age the Science of

2:47

Longevity. So without any further

2:49

ado, here she is Dr.

2:52

Colleen Murphy. Well,

2:55

Colleen, thank you so much for joining me today.

2:58

Thanks for having me. So we're going

3:00

to be talking about your new book, How

3:02

We Age the Science of Longevity. And

3:05

of course, just your general work

3:07

on aging, on the aging brain,

3:10

on the kind of molecular biology

3:12

or, you know, what's going on inside of

3:14

an aging body and brain. And I have

3:16

to tell you, I'm especially

3:18

excited and curious about this

3:20

chat because I approach

3:23

the topic of aging in my

3:25

work as a psychologist because

3:27

I do a lot of older adult

3:29

intervention and I work a lot

3:32

with individuals with cancer, individuals

3:34

with heart failure and things like

3:36

that. So I'm super interested in

3:39

talking about this from a different

3:42

yet coalescing perspective.

3:45

Very different from looking at worms. So

3:48

tell me tell me everything. Maybe

3:50

we start we start with

3:52

your sort of academic path. How did you

3:55

get to where you are now? What did you

3:57

study and what were your sort of research interests? Right.

4:00

So as a graduate student, I was very

4:03

interested in proteins, structure,

4:05

function, like really getting to understand how

4:08

proteins work at the, you know, single

4:10

protein level. And

4:12

I got a really good training in that. And then when

4:14

I was thinking about what to do as a postdoc, thinking

4:18

I wanted to go a little broader. And

4:22

at the same time, my graduate advisor,

4:24

Jim Spudich, recommended that I

4:26

listen to a talk by Cynthia Kenyon.

4:29

And as you know, this was about the same time that she

4:31

was, had just discovered

4:33

that there are mutants and

4:35

C. elegans that live twice as long and

4:37

they're super healthy and youthful. And

4:40

it was also about the same time that

4:44

microarrays were being developed. So you could

4:46

actually look at all the gene transcription going on in

4:49

a cell all at the same time. So that

4:51

seemed like the perfect place to go to try to

4:53

figure out, like, why are these super

4:56

long lived animals? How are they able to live so

4:58

long? And so I went to Cynthia's lab and that

5:00

was a great experience. And

5:02

then at that

5:04

point, I got interested in, when I started my

5:07

own lab a couple

5:09

of years later here at Princeton, asking

5:11

a different question, which is, how can

5:13

we study, how can, you know, keep,

5:15

how can we keep organisms and then eventually

5:18

humans living their best

5:20

life for as long as possible? Which is a

5:22

different question from just, like, living as long as

5:24

possible. And so at that point, we got really

5:26

interested in, can we use these

5:29

little microscopic organisms, C. elegans, to

5:32

try to understand how can we improve memory

5:35

and learning with age and how can we maintain

5:37

reproductive function with age? So those were the two

5:39

big questions that my lab started with. So that

5:41

kind of led to all the research

5:43

that my lab does. And the book

5:45

is really a product of, you know, when

5:47

I got to a point where I could teach a class that

5:49

I really wanted to teach that, looking at

5:52

all the literature in the field. And so

5:54

doing that as a class then put

5:56

me in a position where I could write a book

5:58

that kind of delved into all these different. topics and

6:00

covered other people's work, I hope, in

6:03

some detail. So that's what led

6:05

to the book. So tell me,

6:07

you mentioned that you work with this model

6:09

organism quite a bit called C. elegans, and

6:11

that's like a teeny tiny little

6:13

worm, right? So why is it that

6:15

biologists love to work with this worm, this

6:17

nematode? Yeah. Okay. So

6:21

one thing is that they have a very short lifespan. They

6:23

only live two to three weeks, so average of 21

6:25

days. So what that

6:28

allows us to do is look at these animals. So

6:30

we can actually see them age over time. So it's

6:33

enough time that we can see them age. It's not

6:35

so fast like bacteria where it's there

6:37

and then gone. So we can

6:39

actually, and if you look at a worm under microscope,

6:42

you can see them get fat, they

6:44

get wrinkly and moving

6:47

around well. So

6:50

that allows you to really understand, okay, this

6:52

animal is aging. But as

6:54

I mentioned before, what really broke

6:56

open the field, I think, is not the

6:58

ability just to look at things as they age, because then

7:00

you always have this cause and effect problem.

7:02

You can't tell when you look at something

7:05

with age, is this the equivalent

7:07

of looking at someone's

7:09

gray hair, something that's not

7:11

causative, right? Right. A marker.

7:14

Yeah. Exactly. Age causes that as

7:16

opposed to that causing you to

7:18

age faster. That's a

7:21

really important principle because for

7:23

a long time, even if they were

7:25

looking at gene expression or differences in some genes,

7:28

if they didn't know what the gene did, they wouldn't say

7:30

much about it. But if they had a name for the

7:33

gene or the protein that

7:35

it makes, then they would instantly

7:37

infer some rule for, if

7:39

they saw something goes up with age or down with age,

7:41

but that doesn't really tell you much. So

7:44

this mutant called DAF2, which turned out to

7:46

be the insulin receptor. So

7:48

just a single gene, a

7:51

mutation in a single gene allowed these

7:53

animals to live really long and be

7:55

super healthy that whole time. So

7:58

once you know that, delving into

8:00

it, you can look all the

8:02

way down to the cellular level and really understand,

8:04

well, many things can change with age, but if

8:06

you only keep a couple

8:08

of these things not changing, then the whole animal

8:11

lives in a better

8:13

way. And so that's really what C.

8:15

elegans has allowed us to do all these

8:18

careful studies and really at the cellular

8:21

and genetic level. And usually

8:24

what we find isn't just something strange that

8:26

we find in worms. It's usually someone

8:29

will then test it in flies, find

8:31

the same thing or in mice. And

8:34

then a lot of the genes that we're really interested in,

8:36

the same genes have been found to

8:38

have these single

8:41

nucleotide polymorphisms in very

8:43

long lived people. So

8:46

that tells you that these

8:48

pathways are extremely well evolutionarily conserved,

8:50

and that allows you to then

8:52

start really trying to understand, well,

8:54

okay, what's different? What does this gene do?

8:56

How does it slow things down? That's

8:59

why people love C. elegans because it really is

9:01

an extremely powerful

9:03

research tool. So I

9:05

love that. And you mentioned that when that mutant

9:07

was first discovered and

9:09

then the gene

9:12

or combination of genes that were

9:14

responsible were found that it

9:17

had something to do with an insulin receptor. I mean,

9:20

it's just like a random side

9:22

question, but obviously

9:24

that had a much greater

9:27

impact on the organisms, I

9:29

guess, like longevity or vitality

9:31

than you might expect. But

9:34

is there a relationship between that and

9:36

insulin resistance or type 2 diabetes? Like, does

9:39

that seem to be a contributor to aging?

9:41

Yeah, so it's all a little bit

9:43

confusing because I have to think about the

9:45

direction of it. So let me just start with the

9:47

worms. So, you know,

9:49

before that gene was cloned by Gary Rubkin's lab, when

9:52

people didn't know what it was, they just had a

9:54

name for it called DAF2, which is very unhelpful. It

9:56

just means that the gene has

9:59

a in helping the worms decide

10:01

whether they should go into something called dower

10:03

or not. And actually, I think that actually

10:05

slowed down the field a little bit in the

10:07

sense that people are so distracted by this

10:09

idea that the worms are doing something crazy

10:12

that, you know, other animals don't

10:14

do by going into this hibernation-like state that

10:16

it distracted them from the fact that actually

10:18

the gene itself is the same in

10:20

a bunch of different organisms because they just didn't know. This

10:23

is like in the early 90s before these

10:25

genes had been cloned. Right. We

10:27

often see the outcome, like we did a

10:29

fuck-up long before we understand the structure behind

10:31

it. Exactly. So this

10:34

mutant has other phenotypes as well,

10:36

other effects. So

10:39

anyway, Gary's lab, then Gary Upkin's lab,

10:41

then cloned it and they turned out to be the

10:43

insulin receptor. And instantly when you find that out,

10:45

then you're like, okay, I've heard of insulin. I know

10:47

P-Tb. Right, diabetes. It's like the first

10:49

thing you go to. Exactly. Yeah. The

10:52

most important thing about it is that insulin

10:54

is this key regulator that connects the nutrients

10:56

that we take in with this decision that

10:58

our cells make. Okay. So that's pretty

11:00

well-conserved. So we can think about it in this case.

11:03

See how again, this insulin receptor, it's not a

11:05

no, means it doesn't, it's not a total loss

11:08

of activity. So basically it's dialed down low. And

11:10

so when the worms have the low activity of

11:12

this insulin receptor, they're getting the

11:15

message that they may

11:17

not have that much food around.

11:20

Okay. And there's not a lot of food

11:22

around yet. So then they have to make a decision

11:24

at the full

11:26

body level. Okay. What

11:28

should I do? If they're young adults, what they should do is

11:31

they should slow down reproduction because it doesn't make

11:33

sense to lay a bunch of eggs into an

11:35

environment that doesn't have any food.

11:38

Right. And so a logical thing. So

11:41

slow down your germline. And then also if you're going to

11:43

like plan to that site, say those animals

11:45

are like, okay, well I can hold out for a

11:47

couple of days. I'll keep my OA sites nice and

11:49

healthy, which is finding that my lab

11:51

later made. So when

11:54

times are better, when there's more food around, I need to

11:56

like ramp things back up. Okay.

11:58

But in order to do that successfully. the

12:00

body that's going to lay these eggs has to

12:03

be super healthy, right? So that's how you

12:05

get the signal that goes from the germline to

12:07

the rest of the body to slow down aging.

12:10

Okay, and so that's how it's all connected. And

12:12

so you

12:14

know diabetes is like a disease

12:16

state and it's not the parallel to

12:18

this. We can think of it more like if

12:21

we are in a sort of a low nutrient state,

12:23

then what are the things that our

12:25

body will do to slow down things or

12:28

repair our proteins or things like that. So

12:30

it's the parallels are really, okay. Yeah, it's

12:32

not exactly the same as caloric restriction, but

12:34

for all intents and purposes, like it's that

12:36

that's the parallel logic. I

12:38

guess I ask because sometimes what what

12:42

I see, you know, I do a lot of

12:44

work in sort of the cancer world and sometimes

12:46

I'll see claims made

12:48

that it's almost like that

12:51

there is obviously there's a lot of parallels

12:53

between cancer and aging and there's a lot

12:55

of crossover research, but that like if you

12:57

live long enough, you're definitely gonna get prostate

12:59

cancer or like if you live long enough,

13:01

you know, you might get primary peritoneal or something

13:03

like that. So I wasn't sure if there was

13:05

one of those things like if we were to

13:08

push longevity into an, you know, into

13:12

an extreme if like diabetes will always follow

13:14

or if there was a parallel there, but

13:16

it sounds like there's not like that's kind

13:18

of a pure pathology. It's really non-normative. Yeah,

13:21

so maybe an empty would have a different answer

13:23

to this that would be worth listening to. I think that more

13:25

we should think about it like high

13:27

sugar state. We've also shown that adds to the

13:30

worms it like accelerates and for them, right? Like

13:32

if there's a lot of nutrients you should reproduce

13:34

as fast as possible. There's no need to

13:36

like preserve the body just and slow down aging

13:38

because all the progeny comes. So I think if

13:41

you think about the cells having a similar signal,

13:43

then maybe these this inability like it

13:45

like that it's kind of like getting stuck in a

13:48

state that's unhealthy, right? So I

13:51

think that's probably the best analogy. So yeah, but

13:55

yeah, this is a question like what you're

13:57

asking like if we live long enough, it

13:59

is true. There's some ask like if

14:01

you if you live long enough that

14:03

did nothing to slow down age related

14:06

pathologies Then it is

14:08

true. You'd get a lot of these age related

14:10

disease, right? You know collect them exactly Yeah,

14:13

okay. Our efforts shouldn't be

14:15

to just extend lifespan. They should be

14:17

to slow down all these age related

14:19

diseases Right and it's

14:21

funny because there's obviously a parallel even

14:24

in in psychology to that with like end-of-life

14:26

work that I do which is like It's

14:29

funny. It's kind of a it's a long thread

14:31

that I'm drawing but this I

14:33

don't want to say it's new but Sadly,

14:36

it's kind of new focus

14:38

on You know not

14:41

necessarily life extension medically

14:43

but quality like extending the quality of

14:45

your life Right and really finding that

14:48

balance between are we gonna try and

14:50

do everything medically necessary to extend somebody's

14:52

life if they're miserable Or should

14:54

we be focusing on what are where

14:56

is their quality of life and how do

14:59

we you know prioritize that? So it's kind

15:01

of interesting that in the at

15:03

the individual medical psychological level there are

15:05

parallels with The research

15:07

that you're doing on like whole species levels.

15:09

Like how do we extend life but with

15:11

good quality? Absolutely, and I

15:13

think you know I think when you talk

15:15

to most people who are actually serious about doing research

15:18

in the aging field that's their their focus as

15:20

well They're very aware of the fact. They're not

15:22

just trying to stretch out life. They're trying to

15:25

Now in some cases there's an

15:27

assumption sometimes that everything that will

15:29

extend lifespan will Make people

15:31

healthier and in some cases that's true and

15:33

in some cases it's not true so like that's why

15:35

we have to be a little that's why I'm interested

15:37

in the molecular pathways because distinguishing

15:39

those pathways that extend lifespan

15:42

alone and extend healthy life

15:45

Are interesting and should be distinguished from

15:47

those that just extend lifespan without

15:49

any of the benefits Yeah, you

15:52

know, so it's it's funny I want to

15:54

kind of like take a step back because

15:56

as a person who is scientifically minded who's

15:58

worked in science communication for many

16:00

years as a journalist, but now is not

16:02

spending, I guess you could say, as like

16:05

minute to minute. So some of my information

16:07

is probably a bit outdated. Some of it

16:09

might just be like folk information. I

16:11

think the general idea that comes to

16:14

my mind and maybe this parallel, some

16:16

of the listeners of the show is

16:18

like, I think about aging. I think

16:20

about conversations around telomeres. It seems like

16:22

that was sort of like all the

16:24

rage maybe within the past

16:26

like decade or so. And so I'm curious

16:29

how your work, what

16:32

about that your work kind of focuses

16:34

on or is that like not part of

16:36

the equation or is it a smaller part of the

16:38

equation than we used to think it is? I

16:42

think that the telomere interest

16:44

was like probably peaked in the early 2000s. Gosh,

16:47

20 years, oh God. Don't say that at

16:50

least. That's a dated one. That

16:52

would have been my impression. Now C.

16:55

elegans might be a particularly poor organism to

16:57

look at any of that. So because the

16:59

cells in C. elegans don't turn over. They're

17:02

really good model for looking at parallels

17:04

for all tissues that never turn over

17:07

their cells, their whole lifetime. Oh interesting,

17:09

so they're not constantly dividing, dividing, dividing.

17:12

Okay, all right. They develop to adulthood and

17:14

they have 959 somatic cells. That's

17:17

it, that's all they'll ever get. They

17:19

follow every single cell, that's fascinating.

17:21

Yeah, and so one

17:23

thing is amazing. So if you have a worm like these

17:25

Daf2 worms that are gonna live like six weeks, they do

17:27

that not by having more cells, but like keeping the cells

17:30

that they have healthy, which I think is a good lesson,

17:32

right? But

17:35

I will say that the telomere, you know,

17:37

like the cool thing, let

17:39

me just rephrase it differently. The

17:41

cool thing about the aging field is that there

17:43

are so many interesting discoveries that have been made

17:45

in the past couple of decades that

17:48

are parallel to one

17:50

another, right? And so

17:52

I would say that for

17:55

cells that don't divide, things like

17:57

protein homeostasis and autophagy,

18:00

Things that keep the proteins in the

18:02

cell healthy and allow them to recycle

18:04

the materials and keep their lipids healthy,

18:07

those are all mechanisms that will keep that cell

18:09

that's never going to turn over, keep that one

18:11

working. A cell that's going to

18:13

turn over, I mean, there's an intense interest, of

18:15

course, in stem cells, right? So

18:17

cells that are going to replace themselves, you need to,

18:19

instead of keeping those cells healthy, you can get rid

18:21

of them, right? They can keep up

18:24

toast and die. What's important is

18:26

keeping the stem cells that are going

18:28

to divide and turn into those different

18:30

and turn into those cells, keeping those stem

18:32

cells healthy. And so that's why there's

18:34

this interest in stem cells. It is

18:36

true in order to keep stem

18:38

cells functioning, you need to

18:41

keep the telomeres intact, right? But

18:43

there is that, but it doesn't, I think there's less

18:46

of a thought that, okay, so

18:48

the enzyme that allows the telomeres to

18:51

keep getting replaced, that third one, you

18:53

know, I think several years, many years ago, there was this idea

18:55

of, oh, if you just boosted the levels of

18:58

that telomerase enzyme,

19:00

that you'll then have

19:02

healthier cells. And that

19:04

seems to not have been totally borne out.

19:06

So I think there's so many other factors

19:08

that work. So now there's this idea, you

19:10

know, you probably might have noticed

19:12

in the news, there's some idea that you could use

19:15

what's called Yamanaka factor. So these are these transcription

19:17

factors that are used in stem cells to differentiate

19:20

and become new cells. And the

19:22

idea here is that you could actually generate

19:26

new cells by putting in more of

19:28

these transcription factors. In fact, there was

19:30

a new paper just out this week

19:32

about that. So there's, you know, new

19:34

and different techniques and approaches at the

19:36

molecular level that all might be helpful

19:38

in helping cells and

19:40

eventually an organism keep

19:43

functional longer. So it doesn't, we don't have to

19:45

rely on just one of these pathways. Telomerase is

19:47

not the only thing. Are

19:51

there examples? I mean, we kind of, you

19:53

touched on it a second ago, but I

19:55

think it maybe bears digging a little bit

19:57

deeper. This sort of hypothesis or maybe and

20:00

construct that. In the past, researchers were

20:02

just trying to look at how do

20:04

we extend life at all costs, but

20:07

obviously we don't want to do that

20:09

if it's going to cause a degradation

20:12

to quality of life or to

20:14

functionality. Most aging

20:17

researchers now or longevity researchers now are

20:19

interested in, okay, how do we extend life

20:21

and it be like healthier life? How do we

20:24

make it so that the aging process is actually slowed

20:26

down, not that you age rapidly and then

20:28

you just live in this decrepit form for

20:30

a long time? The question I

20:33

have for you is sort of like, is

20:36

there always a trade-off?

20:38

Does age, does

20:41

the extension of life or does longevity

20:43

always come with you have to give

20:45

something up in order to have

20:47

more minutes, hours,

20:51

days, years? Yeah,

20:53

so that's a popular

20:55

idea that hasn't really been

20:57

borne out by the data. First, we can just start

21:00

looking at centenarians. The people who have

21:02

lived the longest, and again, this is

21:04

not my work. This is a

21:06

study by Nier Bartzleil's lab, I believe. The

21:09

idea was figure out, do centenarians, for example,

21:12

do they just live a long time but

21:14

they are sick much longer? They've stretched out

21:16

that unhealthy part of life or

21:19

something else. What they found

21:22

in this study was, in fact, centenarians

21:24

actually start getting age-related

21:27

diseases much later than other people.

21:30

They don't stretch out the unhealthy period of life.

21:32

What people have been afraid of for a long

21:34

time just doesn't even seem to be borne out

21:36

by even the people who experience extreme

21:38

longevity right now. That's

21:43

the first thing. Then your idea of a

21:45

trade-off, that's an idea that came from evolutionary

21:48

biology. But

21:50

if we look at the data, and that's usually talked about

21:52

in terms of having

21:56

progeny, so the number of offspring, it

21:58

is true that If

22:00

you look at C. elegans even, like you look at these

22:03

insulin receptor mutants or caloricea

22:05

restricted animals, they have slightly

22:07

fewer progeny. In BapTU's case, they

22:09

have two-thirds the number of progeny as wild type

22:11

worms. Wild type worms have about 300. But

22:15

they really stretch that out over a longer

22:17

period of time and they have healthier OSIs.

22:19

So they can have progeny much later in

22:21

life. And so, yeah. And

22:23

so, but if we come back to

22:25

humans, Tom Pearl's lab many, many

22:27

years ago showed, actually this is kind of cool,

22:29

he looked back at like historical data and they

22:32

found that women who lived to be over the

22:34

age of 95 and they also

22:36

lived to be women who had lived to be over

22:38

the age of 100 and they looked at when they

22:40

had their last child. Okay. And

22:42

so it turns out that the women who

22:44

were, would eventually become centenarians, they were able

22:47

to have kids naturally, and this is way

22:49

before they were asleep, IVF or

22:51

any sort of artificial reproductive technologies, they had

22:53

kids after the age of 40. And

22:57

the women who lived to be 95, they had a kid, more

22:59

likely they have a kid after the age of 33. So

23:02

what that tells you is

23:04

that first there wasn't

23:06

really, now I don't know, I can't say

23:08

anything about the number of kids they had, but

23:10

it doesn't seem like there was a trade-off and

23:12

fertility in that direction. They were like almost like

23:15

late fertility was sort of

23:17

a biomarker or a future longevity. And

23:20

so the question is what would be the trade-off if

23:22

you're not talking about fertility? And even when we look

23:24

at individual feelings, we don't see that trade-off. So I

23:26

guess the idea like people would say, like, get

23:29

the feeling you can't have something for nothing. I

23:31

think it's a very human, it's probably cognitive

23:33

bias that we sort of fall victim

23:35

to. Yeah, that's

23:38

interesting. This

23:41

idea of these, like, I know that this

23:43

isn't your research, but obviously for the book

23:46

you had to dig deep and for teaching

23:48

in this area, you have to dig deep

23:50

into this. But I think sometimes we also

23:52

have this maybe misunderstanding because in the media

23:54

we love novelty and we love things that

23:57

are unexpected. And very often you see those

23:59

stories. stories of these women who are, it's

24:01

their 102nd birthday, and

24:04

they're like, what's the secret to a long life? And they're like, drink

24:07

gin and eat cupcakes. And you're

24:09

like, what? And

24:11

so I'm curious if in the

24:13

literature you saw anything about nature

24:17

versus nurture, obviously you're looking at

24:19

the nature, you're deeply invested in

24:21

what's going on genetically and how

24:23

much of the lifestyle factors are

24:26

contributing to this. What is

24:28

that sort of balance? Okay, so one of

24:30

my favorite things to do is collect those

24:32

stories of centenarians and they're always asked, what's

24:35

the secret to your long life invariably?

24:38

First of all, well, yeah, you're right. It's

24:40

always gin or like, so

24:44

I think the only important lesson we can take there

24:46

is that if a

24:48

person's gonna be a centenarian, it kind of doesn't

24:50

matter what they do. It's a sad, it's

24:53

like a- It's a very nature,

24:55

not very nature. Exactly,

24:58

like they were gonna, I mean, there's

25:00

reports of smoking and doing all kinds

25:02

of things you would not necessarily recommend.

25:04

And very few of them, by the way, have been

25:06

like super athletes. Like I know it's actually notable

25:08

when you find someone who's a centenarian

25:10

who was also athletic. So

25:12

it's not like, so I just think

25:14

basically we can learn no lifestyle

25:16

lessons from centenarians because they're

25:19

just like genetic superheroes. Yeah,

25:21

it's sort of like the, sadly the opposite

25:23

of like, if a little kid, really,

25:26

really young child develops a

25:29

childhood cancer, like they didn't do anything.

25:31

Exactly. That wasn't because of carcinogens, it's

25:33

because their cells were already leaning

25:35

in that direction. Exactly, now

25:37

there is a funny thing if you look at,

25:39

since mostly centenarians are women. Oh,

25:42

interestingly enough. Most of all the time. Not that interesting actually.

25:44

I was like, oh, and then I was like, man, okay,

25:46

that's a little surprise. And all of them are like, a

25:49

bunch of them are like avoid men. That's their

25:51

secret. So like- Never

25:54

get married, yeah. I mean, there's

25:56

some interesting sociological say, like the people who are the

25:58

longest live are women. who are

26:00

not married, women who did never married.

26:04

There seems to be, there are social parts of it

26:06

that like people who take

26:08

care of other people actually take on the

26:11

stress of other people at Pierce. So like

26:13

that is actually, and actually we brought up

26:15

telomeres and there's some work by Liz Blackburn's lab

26:17

that has shown that there's stress that affects

26:19

telomere length. And so I think there are

26:21

cases where, you know, the stress of being

26:23

a caretaker does

26:25

shorten people's lifespan. So there's, you

26:27

know, social

26:30

networks actually help protect that. So women have

26:32

sort of like a dual role. They take

26:34

care of other people often, but they also

26:36

like are more likely to have a stronger

26:38

social network than men. And so

26:41

that, you know, that's not, that

26:43

might have like a biological ultimate

26:46

effect that we can study. But right

26:49

now, you know, like when I study C. elegans,

26:51

I can't really study that part of it. Yeah,

26:53

but it is interesting that you see parallels across

26:55

the board. Like we know that women who

26:57

were never married are the happiest group as well.

27:00

And that like married men are happier than

27:02

unmarried men, but married women are less

27:04

happy. And yeah, yeah, that's, it's

27:06

really interesting to look at all of the data

27:08

there. Okay. So we

27:11

do know that there are probably some lifestyle

27:13

factor. I mean, obviously nothing is a hundred

27:15

percent, well, very few things in

27:17

this world are a hundred percent biological, very

27:19

few things are a hundred percent. You

27:22

know, I don't even like the concept of nature

27:24

quote versus nurture, right? Because they sort of exacerbate

27:27

one another. Yeah, you can't always tease them

27:30

apart, but I guess that is important for

27:32

research and really looking at the variance, you

27:34

know, but you're really focused on the, on

27:37

the nature side. Do you do any nurture

27:39

to, I know it's like, probably

27:42

the window is different with C. elegans,

27:44

but do you do any lifestyle

27:46

research? Lifestyle probably is the

27:48

wrong word. Yeah. Yeah. Well,

27:50

I mean, so we like to think about that stuff because

27:52

we like to figure out what can we extrapolate and

27:55

what can we not. And so for a long time,

27:57

I like to say, you know, there were

27:59

these questions about like the. grandmother hypothesis, right? This

28:01

idea that women live longer because

28:04

they contribute to the health and success

28:06

of their grand progeny. And I don't

28:08

think that that's wrong, but we do

28:10

observe, for example, in C. elegans that they

28:12

also have a very long post reproductive lifespan.

28:15

And so for a long time,

28:17

I like to joke that they don't even

28:19

take care of their young. And then it turns out,

28:22

and we did all this work on how

28:24

can you figure out like what post reproductive

28:26

lifespan correlates with, and we had some

28:28

interesting findings there. But more recently,

28:31

I started to change my tune even

28:33

about C. elegans, because you know, what

28:35

is, if you are C. elegans, how

28:37

would you care for your young? You would

28:39

protect them and how can you protect them?

28:41

You could protect them from,

28:43

for example, if you encounter

28:46

a pathogen, so worms

28:48

swim around, you know, they live mostly on rotting

28:50

apples. That's where they find all the bacteria that

28:52

they eat. Oh, okay. Yeah, so

28:54

they're really in rotting fruit. Yeah. And

28:58

so, and in fact, I see it's fun field trip

29:00

last fall, we went to an apple orchard and collected

29:02

a bunch of apples and got all the worms off

29:04

of them, the bacteria. But yeah, so

29:06

if you're a worm and you're swimming around and

29:08

you're like, times are good, there's lots of bacteria on this

29:10

apple, I mean, you eat them, but

29:13

if you encounter a pathogen that smells just like your

29:15

food, what do you do? And so

29:17

it turned out the mothers who eat these

29:19

pathogenic bacteria, they actually eat,

29:22

they get a signal from the bacteria itself. The bacteria

29:24

make all kinds of signals inside them for their own

29:27

metabolic purposes. And it turns out that when

29:29

worms eat those bacteria, they eat the smaller

29:31

RNAs of the bacteria making for their own

29:33

good, and they use that as information, not

29:35

only for themselves, but they actually pass on

29:38

a signal to avoid that bacteria to

29:40

four generations of their progeny. And

29:43

yeah, so that's so cool. So they do

29:45

take care of their young memory. And they

29:47

also, secondly, they secrete this viral-like

29:50

particle that contains that same message.

29:52

So if they're, say they're

29:54

like cousins, eat that, sit that, some

29:56

of that viral-like particle, they'll

29:58

also note, avoid that pathogen in

30:01

the future. Yeah, so it's not

30:03

just about direct lineage. It's like a kinship thing

30:05

as well, just like anybody in my tribe,

30:07

anybody nearby. I

30:09

like that. That's, I mean,

30:11

it doesn't surprise, it's cool, but it's

30:13

like, you're like, okay, yeah, it makes

30:15

sense. It also, it makes me

30:18

wonder too, and I don't know how you could

30:20

possibly research this with C. elegans, but

30:22

looking at the literature, I'm asking for

30:24

my own selfish purposes. Like I just

30:26

turned 40 and I am child free

30:29

by choice, also now

30:31

I'm forced in that direction, but also by

30:33

choice. And I talk about this

30:35

a lot with my friends who either have

30:38

multiple kids, had kids young, had kids older,

30:40

or I have quite a few friends now

30:42

who don't have children at all. And

30:44

how just giving

30:46

birth, but then also raising a child,

30:49

giving those resources over affects

30:51

the aging process. And

30:54

obviously C. elegans, because I think a

30:56

lot of the research, the basic biological

30:58

research is about like these organisms could

31:01

have, could produce offspring, or they

31:03

could produce it much later in life, like you were

31:05

mentioning before, but a worm is not going

31:07

to be like, I could, but I choose not to.

31:11

And so I'm curious if

31:13

you've seen any literature on that, that like

31:15

women who choose not to have children, if that affects

31:17

the aging process at all. Okay, so

31:19

a bunch of things I want to say. So first I will

31:22

say that C. elegans actually, there's a

31:24

very cool assay, it's called the sprinting assay. So there's a fair

31:26

amount, if you put down a hermaphrodite, which these all are, because

31:28

they make both sperm and they'll say, if they

31:30

detect a male, they will run away. So they

31:32

do. I love that. And

31:36

they actually do that until all of their own self

31:38

progeny are done. And when they run out of their

31:40

own self sperm, then they're like, okay. And

31:42

then I guess, yeah, I'll take the

31:44

second best. That's so funny. Okay. Yeah,

31:47

so they actually do this. That's, yeah,

31:49

that's one of my favorite stories about C. elegans.

31:51

Yeah. So,

31:54

look, there's all kinds of things with women's aging

31:56

that I think we're just now starting to understand

31:59

better. finding some starting to be

32:01

more and more good research in this area. Yeah,

32:03

because like more women are doing research about women.

32:05

That's oh, exactly. That's

32:09

really good. Okay, so there's, there's a

32:11

couple different things. So there's having kids.

32:14

And then there's the sort of

32:17

inevitable relationship with just like menopause,

32:19

post menopausal aging. And one of the

32:21

scariest things is that menopause

32:24

actually like the time like this

32:26

is, if you use one of these, what's called

32:28

an aging clock. So Steve

32:31

Horvath developed this way of looking at DNA

32:34

methylation. And if you use this clock, so

32:36

he and Morgan Levine found that if you

32:38

look at women who

32:40

have gone into menopause either from

32:43

surgery or naturally, there's

32:46

actually this increase in the rate of aging at that

32:48

point. So that's

32:50

a little bit kind of like it matches our expectation,

32:52

but a little bit scary. And

32:55

that's going to happen whether or not someone has kids, right?

32:57

So they look

32:59

at whether hormone replacement, so

33:03

in that study, they did and actually showed that

33:05

it's loaded down by their clock metric.

33:08

Interesting. Yeah. So

33:10

that was pretty interesting. So there's a lot of lessons in

33:12

there. It is true, these, you know,

33:14

these studies of like, more like

33:16

demar, like how long do who

33:18

lives the longest? It seems that having

33:20

two kids is like the optimal number of kids. If you're

33:22

going to anything more than that, the lifespan

33:25

of the women went down. So yeah. But

33:28

what about not having kids at all? Has anybody

33:30

looked into that? Somebody probably has. And

33:32

I probably have a lot of paper on that. I

33:34

think that that

33:37

I would probably have to come back to that. I do think that women

33:39

without, mostly it's come down

33:41

in terms of women who never been married, lived the

33:43

longest. Yeah. And I think it's

33:46

so funny because so much of our literature,

33:48

you know, you think that it's agnostic to

33:52

the patriarchy or you would think that, and of course

33:54

we don't think that, but some people might think that

33:56

like, that's the science is science and it's like no

33:58

science is done by people. we have all of

34:00

these guys in these normative things. It

34:03

makes me think that women who choose not

34:05

to have children, they

34:09

weren't considered as a group in the past. It

34:11

was like, you didn't have kids, there must

34:13

be something wrong with you. So

34:16

that would be the idea, well,

34:18

these women were infertile and so they're in this

34:20

group for our research. But this idea that- Yeah,

34:22

I think I have to move back. It's

34:25

probably something in some paper that I'm overlooking. So I

34:27

don't want to distance the authors who actually did the

34:29

hard work on that, but I'm just not

34:31

off the top of my head remembering- Yeah, I wouldn't be surprised

34:33

if it's just not a common area or

34:37

it's not a common group within

34:39

the literature. Should

34:41

be historically, right? Yeah, right. Because yeah,

34:44

there's like an assumption that there's a

34:46

reason behind it that's biological or that's-

34:48

And maybe now that will be more

34:50

studied as more and more people choose

34:52

not to have kids. Yeah, I hope so. I

34:57

feel like there's a working hypothesis here. I

34:59

definitely feel like when I meet women who

35:01

have had, or my friends who are dealing

35:04

with raising littles, they're

35:07

looking rough. It's

35:09

hard to know if it's an aging figure,

35:11

if it's just like a need to sleep

35:13

more, yeah, exactly. And we

35:15

know that sleep is very important. So it's

35:17

not like, it may not be direct. I think

35:19

that's a real question was to set up the

35:21

scientific question, is it having kids or

35:23

is it like being so tired and sleep

35:26

deprived for such a large chunk of your life

35:28

that is having an effect on aging?

35:30

I think that would be a

35:32

good question to answer since we know sleep is

35:35

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to learn more. Yeah,

36:38

and or a lack of the amount

36:40

of time and effort and energy you

36:42

can put into like self-care, you

36:45

know, which sleep is a huge component of that, but

36:47

so it's just like rest and

36:49

engaging in like, I don't

36:51

know, leisure or engaging in

36:53

activities that are mentally

36:57

challenging. Or I can imagine that a lot

36:59

of these things might contribute, but again, these

37:01

are all lifestyle factors that as you sort

37:03

of mentioned, the variance

37:06

there feels like it might be

37:08

lower than we'd hope. Yeah,

37:12

so a lot of a lot of

37:14

what we're talking about is sort of luck of the draw. Like

37:17

what kind of genes did I get from my parents? Do

37:19

you find that longer-lived

37:22

people tend to produce

37:24

longer-lived people? I mean, when we talk

37:27

about something that's at the molecular level, at

37:29

the cell or the genetic level, you would

37:31

assume that. Yeah, so definitely look for

37:33

the people who are at the end of these, people

37:35

with extreme longevity, one

37:39

of the best predictors is kind of a useless piece

37:41

of information by the time you find it out, but

37:44

one of the best predictors is if you're going to

37:46

live long is if you have a long-lived sibling. Right,

37:48

yeah. But

37:52

you know, parents, lifespan,

37:55

things like that are very... The

37:58

amount of... Longevity

38:00

that is genetically determined free to that's

38:03

been studied by many groups, and and

38:05

as Six Six is that there's been

38:07

sort of like a couple. Different schools

38:09

of thought. One of course

38:12

is that and there's a huge genetic

38:14

component everything And for the people have

38:16

the specific variance like there's a couple

38:18

of variance arms things In April he

38:21

and Saxo Three A said oh sees

38:23

are so strong that these. Longevity.

38:26

A Lille that accent. It doesn't matter what else

38:28

is in the background. But. Them for

38:30

everybody else. Actually don't want to make sure

38:32

that we distinguishes of the singer says centenarians.

38:34

From everybody else because. For.

38:36

Everybody else. All these lifespan, lifestyle factors

38:38

are super friends. Rate what we eat,

38:41

how much exercise we. Get. How much

38:43

sleep? So unless you know that you have

38:45

the barry this can adapt to new to

38:47

be a centenary you probably should see a

38:49

lot of attention to your your health. I

38:52

see so like if. I may not

38:54

live to be like. A. Hundred and sixteen

38:56

years old by. How

38:58

I treat my body and what I do

39:00

now could make a huge difference between if I

39:02

die at eighty or ninety or seventy or eighty

39:05

here in a shining attitude. Yeah to an

39:07

end. The. Problem with this says it's it's

39:09

all the boring. Stuff that we already

39:11

knew sprayed like arm and kind

39:13

of the no fun stuff like

39:15

he festivals I'd rather be nice

39:17

to get sometimes when people. Harm.

39:21

You know, listen to these things

39:23

are going. To. Read my book.

39:25

Isn't that they're looking for like that one

39:27

magic bullet that's gonna like. Make sure that

39:29

they don't have to do anything else in

39:32

a season and let their genetic variants arm

39:34

in out. I did all adds up right?

39:37

Ear. Sabha. Yeah

39:40

what? Wow. But when we talk about the

39:42

genetic variants these kind of like super agers

39:44

or than money on of like the opposite

39:46

of what I'm trying to say. not somebody

39:48

to ages. That yeah

39:50

they're literally called the have a get somebody

39:52

that is male or a to thriller have

39:54

some. So when. You look at like a

39:56

model organism like the elegans do. The. Really?

39:59

Tell. The heck did ones like

40:01

the Super Age or See Elegans tend

40:03

to give? Birth. To the give

40:06

birth Saturday the ideally and create a

40:08

guess. Yeah, so do they tend. To

40:10

have offering that are also super agers.

40:12

Yeah. Absolutely so that that she is

40:14

it that's completely genetically to so each.

40:16

we know those me and now what's

40:18

cool that though is within our population.

40:20

Say you have a hundred animals. They're.

40:23

Genetically identical case, they don't have dropped

40:25

it on the same day, the runway

40:27

and race as a what's really cool

40:30

to look at. And. This is

40:32

worth that. My lab did on couple

40:34

years ago. In collaboration with a

40:36

group and in Korea with sense if

40:39

you take say one hundred worms. And

40:42

you every day pick that those ones

40:44

offer play in you film them. Like.

40:47

Crawling around on a plate. You. Can

40:49

track how fast they move and you can even

40:51

track where we discover was if you track their

40:53

maximum speed as like the moment when they started

40:55

sprinting. I'm. Back goes

40:57

down with age. Can win

41:00

their middle aged. You can predict which ones

41:02

are going to live long. By. Separating.

41:04

Them into the ones that have a really fast

41:06

maximum velocity versus the ones that have a slower

41:08

maximum velocity. So. Even

41:10

within that, like the identical

41:13

isogenic population. They're still

41:15

captivity. And it. but it's predictable

41:17

based on something we can see in middle

41:20

age. And. I love this the

41:22

his it completely pulled the rug out of

41:24

that do remember that ridiculous. Thing. That

41:26

trump said several years six when he was

41:28

like i don't like to work out too

41:30

much this is only like so much energy.

41:32

Somebody as in their life a lot want

41:35

to use it added magneto it would be

41:37

opposite of that. My first. Yeah

41:39

now he said nothing about like number of heartbeats. Or

41:42

something. Zealand? Yeah. But

41:45

what you're saying is basically that those that.

41:47

Are kind of blake have more energy

41:49

or healthier. Kind of like go in

41:51

a little bit harder. But not not

41:54

to an extreme, just the date

41:56

they're showing this capability. Of.

42:00

you know, metabolic strength, they're showing that

42:02

they can like show off they can,

42:04

they can go. Yeah, that's a good

42:06

thing. Yes, biomarker is predictive of a

42:08

longer life, not the other way around.

42:10

They're not burning themselves out of energy

42:13

faster. Yeah, exactly. And that's been shown

42:15

for I think a lot of that's a big part

42:17

of the field is trying to figure out what

42:19

are those what are other proxies that we

42:21

can measure in life that would tell us

42:24

how healthy someone is going to be for

42:26

many years. And so is that a blood

42:28

thing? Is that like you know, experimental

42:30

tests we need to do on people. So

42:32

there are people in the field trying to

42:34

figure that out. And I think that's gonna be really

42:36

helpful for us. Because if you could figure out people

42:38

who are going to live shorter, then maybe you'd want

42:41

to help them. Yeah. Exactly. Yeah, or like, yeah, it's

42:45

just kind of like, what

42:47

do you call it

42:49

like? Gosh, why am I blinking on

42:52

the word but just like, yeah, protective medicine, like

42:54

doing things early as opposed prevent

42:56

the thank you as opposed to

42:59

treating something after it already happens. Exactly. What

43:02

you say for American medicine, we're very good

43:04

at treating things after their problem,

43:06

but not really preventing them.

43:08

So we need to get better at that. But

43:10

I guess I would also ask

43:13

how often in that kind of research,

43:16

whether we're talking about something like at the

43:18

molecular level that almost feels like it doesn't

43:21

translate, even though does translate, it's like you've

43:23

got to go many, many steps to translating

43:25

it to, let's say, biomedical

43:28

research on human beings. How

43:31

many times though, are we

43:33

doing these deep dives and then kind of the

43:35

outcome is well, yeah, obviously, it's like exercise and

43:38

eat well. Right.

43:40

Okay, so I mean, that's

43:43

true. But the reason that we're studying it

43:45

isn't to like necessarily stop at telling people

43:47

what they should eat or how much exercise

43:49

they should get. The real basis

43:52

of a lot of the research that's going on in

43:54

all these different labs is to understand, well, what does

43:56

exercise do? What does eating less do

43:58

so that you can understand The molecular level,

44:01

what they do, and then. Could.

44:03

You Okay so that somebody who is like.

44:07

Sluggish. You can tell people not eat so much

44:09

sense for the exercise. Is there already healthy and able

44:11

to do that? But say someone is like. Like.

44:14

In a wheelchair and can't necessarily

44:16

exercise as much like or something

44:18

like that wouldn't be helpful if

44:20

you could understand what that molecular

44:22

target of you know clerk restriction.

44:24

Or exercise is and then develop a drug

44:26

to that to give to people says a

44:28

cash kind of like. Jumpstart that

44:30

in them. Or

44:32

someone who is suffering early from some for

44:34

age related disease to we give them a

44:36

drug that mimics. Those are called

44:38

like on. Clerk or City Metics if

44:40

you give them a drug that would mimics

44:42

the state of clerk restrictions. And.

44:45

Could they be healthier? And that's actually

44:47

the idea behind the lot of these. Some

44:49

were legacy, now some these. I'm. Clinical.

44:52

Trials of things like Metformin, Iraq and

44:54

Son. Rates. Of it. maybe we can

44:56

figure out how to help people be healthier. Interesting.

44:59

And curious as a scientist and as

45:02

somebody who you know is speaking in

45:04

the media and probably has at least

45:06

some amount. Of your finger on

45:08

the pulse of sort of the

45:11

public communication component of. Aging

45:14

and Wellness Reserves Or as I

45:16

should say, Wellness. I'm not research, but

45:18

Wellness. Wherever

45:20

the like? Fans of yours? Yes

45:23

sir. how often are you like

45:25

screaming into the void rolling your

45:27

eyes at like the amount of

45:29

pseudo science. And the amount of

45:31

sort of like self help stuff that

45:33

is, you know, moving into bullshit. Territories,

45:35

it's like worrisome for yeah. Yeah.

45:38

It's constant. Straight.

45:40

That regard never ended illusion unforeseen. I'll

45:43

be a because I do a lot

45:45

of research for the book. I'm. Now.

45:48

Google things I'm interested in every one of

45:50

these ridiculous things and so like I get

45:52

caught and notices the prom it and so

45:54

one of the messages on the reason I

45:56

really want to. The. Field to

45:58

understand What are the molecular. targets

46:00

of these interventions might be is so

46:04

that eventually we'll

46:06

have good FDA clinical

46:08

trials of things so that someone

46:10

can't just sell you something through

46:12

Facebook that actually is junk. That's

46:16

one of the good efforts

46:18

in the field is to ask, okay,

46:20

is there something called the TAME trial?

46:22

Again, this is near-bartholized efforts

46:25

to try to get

46:27

metformins classified as

46:29

a longevity treatment

46:31

drug because by

46:33

doing a clinical trial that really looks at what

46:35

does it do to people, what are

46:38

the effects, how

46:41

long do you have to take it, and are

46:43

there in the blood, like, can you see diagnostic

46:47

blood biomarkers that are

46:49

helpful? Because right

46:51

now we're in the state where there's things like

46:53

nutraceuticals, which people can just sell you

46:56

stuff and say that they have some

46:58

great effect. How would you know? Yeah, because they're,

47:00

quote, vitamin, so they're not even regulated by the

47:02

FDA. It's like a whole thing. Exactly.

47:05

That's a little frustrating.

47:07

The other thing that,

47:10

particularly a vaccine to me, is the idea that

47:12

we've figured everything out already and so people

47:14

should just go on some diet or something

47:16

and adjust it a little. Yeah, that worries

47:19

me a lot. Yes, all the woo-woo stuff

47:21

that people try to sell is scary, but

47:23

I think even more worrisome are these lifestyle

47:25

influences that are just like, you need to

47:28

just fast all the time. I

47:30

can see them making that leap,

47:32

even listening to this interview with

47:35

the conversations about caloric restriction

47:37

or about keeping your

47:39

sugar low and all of those things and the links between,

47:41

that they would be like, okay, so I should just not eat. It's

47:44

like, no, no. Yeah, and that's

47:47

worrisome to me. First of all,

47:49

there's people who really enjoy doing that. In

47:51

my experience, it's not entirely men, but it's

47:53

almost all men, and they would definitely tell you

47:55

that they're doing it. There's

47:58

lots of good scientific backing for that. from

48:00

model systems research. So I'm not saying that they're wrong.

48:03

But when it comes to humans, I

48:06

think it's, when we're talking about quality

48:08

of life, eating is part of quality of

48:10

life. And I don't think it's particularly useful

48:12

to like say that everybody should

48:14

be, color

48:16

of their sickness themselves all the time because it's really not,

48:19

or, you know, not that great. There's

48:22

also a level like you can go too far

48:24

and it's really detrimental to your health. And of course,

48:26

you can have that more often in women sadly. So

48:28

it's like, exactly. One

48:30

of the things I talk about in the book, you know, like, a

48:33

lot of these guys who are promoting

48:35

this, they have not been bombarded with

48:37

messages since they were pre-teens about how

48:39

skinny they should be. And

48:41

so I think they're kind of

48:44

missing that and the idea of like eating

48:46

disorders and things like that. So anyway, that's

48:48

completely fraught and also under represents the

48:50

science that's been done in the field to

48:52

really understand the molecular mechanisms of all this

48:55

stuff that I'm really interested in. Yeah.

48:57

There are other ways to have these

49:00

conversations that aren't so, I think that's,

49:02

again, it comes down to this like

49:04

very deep cognitive bias that I don't

49:06

wanna blame on nature. I think there's

49:08

a heavy nurture component that we reinforce these

49:10

cognitive biases, especially through our politics

49:12

and through the way that we

49:14

structure our education. That's like this

49:16

very black and white thinking approach

49:19

to life, right? Like, oh, well, I

49:21

heard this thing. So it's always definitely gonna be

49:23

this way. And it's like, no, there's so much

49:25

gray, there's so much nuance. And there's almost never

49:27

a simple answer or a quick fix. That's

49:30

why we're digging deep into, like

49:33

that's why this conversation has been going on for

49:35

46 minutes, right? We didn't have to, we couldn't

49:37

just have this conversation in two minutes and be

49:39

like, okay, call it a day. It's just sadly

49:42

science doesn't work that way. And I think that's

49:44

why in the sciences, we often

49:46

are frustrated by

49:48

self-help or pseudoscience

49:51

industries because they get

49:53

to. Yeah, you can feel particularly

49:55

weird because then you have these individuals who

49:57

are like taking the drug that they developed.

50:00

or it's weird like

50:02

this doesn't happen I think in other

50:04

fields where somebody is actually like you

50:07

know trying to do some experiments on themselves.

50:13

That's kind of weird. Now I do think in

50:15

some cases like if you are ill

50:17

from some disease

50:20

or especially metabolic disorder you know like I

50:22

think there are cases where things like intermittent

50:24

fasting and caloric restriction could be really helpful

50:27

and I think there was a study that just

50:29

came up this week showing that all these blood

50:31

biomarkers get better. So I think there are

50:33

cases where like you might want to do that. For

50:35

sure. There are also cases where like going into

50:37

ketosis is healthy right but like for a lot

50:40

of people who are like no I want to

50:42

just eat keto all the time and have all these ketones

50:44

in my list like okay. Yeah. There's

50:46

a lot of people with a logical component

50:48

to all of this. It's not particularly great so

50:50

about like that. I

50:52

think I get brushed under the

50:54

rug because as I've been saying recently

50:57

like if you give

50:59

a C. elegans who's been fasting a choice

51:01

they will pick the food right. Right.

51:04

Yeah that's true. Yeah

51:06

there is something there that's deeply programmed

51:08

in us. I hate using that word

51:10

but yes we are we are still

51:12

alive. We are biological organisms who have

51:14

a life drive right who

51:17

are going to do the things that we you

51:20

know even without thinking about it that

51:22

are protective. Interesting. Okay

51:25

so I've got to ask because we're like running

51:27

low on time. Is there anything we've talked about

51:29

a lot of stuff but I didn't really follow

51:31

the structure of the book I meandered a lot.

51:33

So is there anything like big surprises or big

51:35

takeaways that we didn't tap into that you'd be

51:37

like no no we can't end before your listeners

51:39

hear this. Oh

51:41

my god now I have to think about all the stuff in my book. Oh

51:44

okay. You know the

51:47

reason again this is not really a self-help

51:49

book but I do think that understanding what

51:51

I want readers to understand is like if

51:53

we if we can really deeply understand the

51:55

molecular mechanisms that play into

51:57

aging and longevity then. And

52:00

like I said, it's actually kind of really exciting time.

52:02

There are a bunch of, and I don't have any

52:04

connection with any of these companies or biotechs, but there's

52:06

a whole bunch of biotechs that have taken off in

52:08

the past couple of years that are looking

52:11

at many of these different pathways that

52:13

have been discovered in developing

52:15

drugs that could help people. And I'm excited about

52:18

this because I don't think it's selfish to think

52:20

about, like I used to be worried, oh, you

52:22

know, we're going to make a drug and only

52:24

rich people will get it and now,

52:27

you know, increase the inequalities that we

52:30

already see. But what I am

52:32

hoping is that because there's so many of these different approaches

52:34

that are happening that maybe some of them

52:36

will be very accessible. And also

52:38

that some of them may help not just people who

52:40

are elderly, but also people

52:42

who have other problems, even in midlife. And

52:45

I think that's something like, for example,

52:47

I saw an interesting talk about analytics

52:49

being used to treat people who

52:52

are survivors of childhood cancers. So these are

52:54

people like in their middle life or having,

52:56

and that's exciting, right? Because then you're like

52:58

helping a broader group of people than just

53:00

like people are, you know, concerned about living

53:03

forever. So yeah, and also

53:05

like, like I said earlier, there's

53:07

so much crossover sort of between

53:09

aging research and cancer biology research

53:11

that yeah, I could see that

53:13

sort of unintended there would be

53:16

these discoveries

53:18

that then somebody else who studies something else is

53:20

like holy wow, I got to dig into this and

53:22

then something else comes out of it. That's

53:24

right. So I think there's a lot of good

53:26

effects that we usually think about all the terrible

53:29

things that will happen. But in fact, I

53:31

think there's going to be a lot of good things that

53:33

will happen. But they're kind of we're on the cusp of

53:35

that. They haven't come yet. So anyone who's telling you they

53:37

have all the secrets and they know the secret to long

53:40

life probably doesn't really. But we're actually

53:42

getting a point where there's going to be something that can

53:44

be taken for a lot of these. And I

53:46

just want to say one last thing, which is kind of crazy about

53:48

when you're talking about food and stuff is that these are these

53:51

things about some of the gluteids and

53:53

they seem to be like kind of miracle

53:55

drugs that I think are going to be

53:57

like kind of longevity drugs in the sense that They're

54:00

going to help people who would have

54:02

other.otherwise died early of cardiovascular disease. They're

54:04

going to extend their lifespans. And

54:07

so I think it's an interesting that we've

54:09

already have a just Like a Thing that

54:11

I like even mainstream at this point on

54:13

that is kind of right in front of

54:16

us that we might consider to be a

54:18

longevity Drugs Somewhat yeah that is interesting. This

54:20

idea of sort of like what's already in

54:22

the with already available in are we using

54:24

it the right way or can we think

54:26

about it and a new way? I love

54:28

that will. Okay, so I haven't done this

54:31

in a while because I've forgotten. So apologies

54:33

my listeners but I historically always ask my

54:35

guess the same to questions is closing. Questions

54:37

at the end of the show. They're

54:39

sort of really big picture but you

54:41

can answer them however you'd like. So

54:43

basically I want you to think about

54:46

whatever context. Fields relevance you right now. so the

54:48

seat I know you're in the lab. literally like you've

54:50

locked yourself off to be able to talk to be

54:52

so this could. Be with your work that

54:54

it could be personally, could be family,

54:56

it could be community, even global or

54:59

cosmic. The first question

55:01

which is the bummer questions we get it out

55:03

of the way is when you think about the

55:05

future, what is the thing that's keeping you up

55:07

the most at night? The thing that is most

55:09

concerning for you? maybe even your bordering on like

55:11

pessimism or cynicism and then on the flip side

55:14

of that to and. On a more positive,

55:16

know where are you finding your hope? Your

55:18

optimism? Like what? are you really looking forward

55:20

to? For. For the second question

55:22

I think. I just answered that with other I

55:24

for on the brink of of discovering on a

55:26

since I was a for that first question actually

55:28

the things that I'm. Certainly. While

55:30

writing this book was even if we

55:32

could solve all these problems in the

55:35

longevity fields maybe the a miraculous like

55:37

medical breakthroughs than that? Is

55:39

not going to matter if you know our

55:41

ears is heated up so much the we

55:43

can't can live on in Monterey. I

55:46

think that I'm happier. Shanahan Afraid to try

55:48

to help people live as on path we

55:50

need. To do a better job addressing

55:53

climate change problems. And so that probably

55:55

the thing I don't work on, but like

55:57

I think that is really. important to keep

55:59

in mind we're talking about long life. Yeah,

56:02

that's, I mean, great way to put it. It's

56:04

all synergetic, right? Like you're doing all this research

56:06

on how to live longer, but what's the point

56:08

if we don't have a place to live? Yeah,

56:10

no. Well

56:12

said. Well, everybody, the book is How We

56:14

Age, The Science of Longevity by Dr. Colleen

56:17

T. Murphy. Colleen, thank you so much for

56:19

being here, for enlightening us. It's been a

56:21

really interesting and

56:24

exciting chat. So thanks for sharing your time with

56:26

us. Well, you're welcome and thanks for having me.

56:29

And everybody listening, thank you for coming back week after

56:31

week. I'm really looking forward to the next time.

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