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Venki Ramakrishnan: The Science and Hype of Living Longer | Podcast | In Good Company

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Venki Ramakrishnan: The Science and Hype of Living Longer | Podcast | In Good Company

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1105 segments

0:01

Hi everybody and welcome to In Good

0:03

Company. I'm Nicolola Tangan, the CEO of

0:05

the Norwegian Sovereign Wealth Fund. Now

0:08

longevity is one of the hottest topics

0:10

in the world right now. Billionaires are

0:13

pouring money into it. [music] You know,

0:15

when they were young, they uh wanted to

0:17

become rich and when they are rich, they

0:19

want to become young. The wellness

0:21

industry is selling it and opinions

0:24

about how to live longer and everywhere.

0:27

So we wanted to find out what is real,

0:29

what is hype and how close are we to

0:32

live forever. To help us answer this,

0:34

I'm joined by Sir Weni Rama Krishnan,

0:37

the noble winner in chemistry, former

0:40

president of the Royal Society and

0:41

author of the incredible book Why We

0:43

Die. Weni, warm welcome.

0:46

>> Thank you.

0:46

>> You start your book with the pharaohs of

0:50

Egypt who believe they could transcend

0:53

death. Why did you begin there? Well,

0:56

the pharaohs are an interesting story

0:58

because humans try to avoid death by a

1:01

variety of strategies.

1:04

Plan A is simply to try not to die. Plan

1:08

B is to try to believe that even if you

1:11

die, your whole body will be resurrected

1:14

and you will go to some paradise.

1:17

And plan C is that maybe your body will

1:20

decay but you will have an immortal soul

1:23

that will uh you know outlast you and

1:26

you can occupy other bodies and so on.

1:29

>> So now many thousand years later how

1:32

close are we to living forever?

1:34

>> I think there's no physical or chemical

1:36

law saying that our lifespan has to be

1:40

uh what it is today. I mean if you look

1:42

at it today we can expect at the most to

1:45

live to be about 110 to maybe 120 years.

1:50

Only one person has exceeded 120 years.

1:54

Uh but saying there's no physical law

1:57

doesn't mean anything because you know

1:58

there's no physical law that we can't uh

2:01

eventually colonize other galaxies. But

2:04

if you look at all of the difficulties

2:06

involved even in, you know, going to

2:09

Mars, uh, you realize that it's

2:12

incredibly hard. And so I put a this

2:17

long life extension, hundreds of years

2:20

in that category, you know, which is

2:23

highly unrealistic today, despite what,

2:26

you know, you may hear from various uh

2:29

people promoting hype. Before we uh kind

2:33

of dig deeper, how do you define aging?

2:35

>> Aging is I would say the gradual loss of

2:39

function of our systems. That is from

2:42

our molecules, cells, tissues to the

2:45

entire body. It gradually loses function

2:48

due to accumulation of damage and

2:51

changes with time.

2:53

>> And and that's how I would define aging.

2:56

Now, it has external manifestations. You

2:59

know, you you can't walk as fast. you

3:01

don't you're not as strong, you're more

3:03

resist more susceptible to infections,

3:06

you know, so there are many external

3:08

manifestations, but underneath it are

3:11

these accumulated damages to our cells,

3:14

tissues, and ultimately comes from our

3:17

molecules.

3:18

>> Well, you are 74. I can't see so many

3:20

external manifestations in you. But

3:22

>> well, I I'm lucky because I have a dark

3:24

skin in a northern climate. So that

3:27

gives a superficial

3:29

uh you know illusion. But if you if you

3:33

were to look at the inside of my body,

3:35

you you would find it's quite old.

3:37

>> Well, we should talk about that later.

3:39

But it seems like two ideas are getting

3:41

a bit blurred, right? So extending life

3:43

means slowing the aging process and then

3:45

rejuvenating cells means making old

3:48

cells young again. So what's the kind of

3:49

that difference between the two?

3:51

>> Okay, so most uh anti-aging strategies

3:55

have to do with preventing damage or

3:58

slowing down uh the you know damage and

4:01

and dysfunction. Okay. And but some one

4:06

class of strategies involves trying to

4:09

get cells to go backward in development.

4:13

And if you the way to think about it is

4:15

a fertilized egg can develop into every

4:19

kind of tissue in the body. That's what

4:21

it does, right? And the if you look at

4:24

the early embryo, it has many cells, but

4:26

each of those cells could become any

4:28

type of tissue. Those are called

4:31

pluropotent stem cells. But as the

4:34

embryo develops, the stem cells become

4:36

specialized. So some cells can only make

4:41

cells of the blood system, others can

4:43

only make cells of the nervous system

4:46

and so on. There are many types of cells

4:47

but still a small class of cells. Now

4:53

the way but this process normally never

4:55

goes backwards except in real life it

4:58

does. For example, the child born of,

5:03

you know, old parents like 30-year-old

5:05

parent, uh, it starts the clock from

5:08

zero, right? And in fact, the child born

5:11

of a 40-year-old woman is not older than

5:14

the child born of a 20-year-old woman.

5:17

So, at some point, you know, there is

5:18

this resetting.

5:20

The resetting is not completely perfect

5:22

but because there's a lot of selection

5:24

involved in birth you know all the any

5:27

cells that are defective or simply don't

5:29

make it uh to a full grown [snorts] uh

5:32

ch child. So that's the process that

5:36

people are trying to reverse. And the

5:38

first proof was when John Girden took a

5:42

skin cell from a frog

5:44

>> and took the nucleus and put it into an

5:47

egg and could grow a completely brand

5:49

new frog that was a clone of the

5:51

original frog. This showed that you

5:53

could actually reset the clock in a skin

5:56

cell [snorts] and make it develop into a

5:59

whole new frog again. And then Yamanaka

6:02

showed that only introducing four genes

6:06

into uh some cells, any cells can can

6:10

make it go backwards all the way to that

6:13

early form of a stem cell.

6:17

>> And that's the logic people are trying

6:19

to use. Now, of course, you don't want

6:21

to make all your organs go backwards all

6:24

the way back to pluropotin stem cells

6:26

because that there would be a big

6:28

confused mess and you would get tumors

6:30

and so on. But people are asking, can

6:34

you make this program go backwards just

6:37

a little bit so that the cells still

6:40

maintain their identity? the skin cell

6:42

stays a skin cell and the muscle cell

6:45

stays a muscle cell or the liver cell

6:47

stays a liver cell and but but it's

6:50

slightly backwards in development

6:53

>> you know has gone backwards so you can

6:55

think of it as a way of trying to

6:57

reverse the aging clock and that is a an

7:01

exciting area but you know making it

7:04

work in humans in a safe and effective

7:07

way it's not clear how long it'll take

7:10

>> no What's actually going on inside our

7:13

cells as we get older?

7:14

>> Well, many things happen. So, one is

7:16

that our molecules get damaged and a

7:20

primary source of damage is if you

7:22

damage your DNA so that uh you know it

7:27

it is problematic. It results in two

7:30

things. One is the cell can sense the

7:32

damage and it can send the cell into a

7:36

program called scinessence where it

7:38

doesn't function normally and in fact

7:41

creates secretes inflammatory compounds.

7:45

Now early life this is a cancer

7:47

prevention mechanism because if you have

7:50

to damage DNA you don't want that cell

7:52

to hang around because it may mutate

7:54

into a cancer cell right and so this is

7:57

a mechanism to get rid of these cells

8:00

where damage is sensed but if the damage

8:02

persists it can also alter the genes

8:05

that are you know part of the genetic

8:08

program and that can also cause

8:10

dysfunction. So there are ways that you

8:14

know molecular damage can cause

8:15

dysfunction. Now this kind of damage

8:18

then results in the cell itself not

8:22

regulating itself properly. The organels

8:25

in our cell called mitochondria

8:28

which have their own DNA but also

8:30

interact with the rest of the cell they

8:32

also can get damaged uh quite a lot. So

8:36

you can see these kinds of damages occur

8:39

due to all kinds of things. Exposure to

8:42

chemicals even water uh alone can cause

8:45

DNA damage that's that was uh discovered

8:48

by Thomas Lindal [clears throat]

8:50

>> uh for which he won the Nobel Prize. So

8:52

just the act of living causes damage but

8:55

we have sophisticated repair mechanisms

8:59

that constantly repair the damage but at

9:03

some point the damage starts

9:04

accumulating with age.

9:07

>> Those mechanisms are never perfect.

9:09

>> Talking of which so um a century ago uh

9:12

most people died when they were 50 or

9:15

before and today the average uh is

9:17

roughly 80. You mentioned one person had

9:20

made it to above

9:23

120. So why has that ceiling not moved?

9:26

>> Okay, this there's a difference between

9:28

the average and the ceiling. So life

9:30

expectancy has doubled in the last 150

9:33

years, but that's mostly due to

9:36

improvements early in life. For example,

9:39

infant mortality has gone down. Uh you

9:42

know, many infectious diseases uh can

9:45

now be cured. So and accident rates have

9:49

have been reduced dramatically. So all

9:52

of those things mean that we can live to

9:55

an older age. So the average has gone

9:58

up. Okay. But even in the 1500s,

10:01

Michelangelo lived to be almost 90. So

10:04

it's not, you know, that nobody lived to

10:07

be an old age in the in olden times.

10:10

It's just the average was low. and and

10:12

we solved it by public health and

10:14

vaccination and nutrition and medicine.

10:17

Okay, those are the four uh big things.

10:21

But as you get older, then aging starts

10:23

to kick in and that we've not actually

10:26

uh made a lot of progress in. And so the

10:30

maximum lifespan has not actually

10:32

changed a lot. It's changed a little bit

10:34

because you know people do live longer

10:37

and so more of them make it to over 100.

10:40

For example, the number of people over

10:42

100 is increasing everywhere.

10:44

>> I think the prime the prime minister

10:46

typically in the past sent letters to

10:48

everybody turning 100 and then suddenly

10:50

became just too much work. Right. In

10:52

Japan, they produce more diapers for old

10:54

people than for babies.

10:55

>> Yes. That's that's a whole another

10:57

problem. What is happening is society is

10:59

getting older but but people the

11:02

fertility rates are going down.

11:04

>> Yeah.

11:04

>> So society is becoming skewed towards an

11:08

older population. But how do we crack

11:10

this 120 year barrier? What do you think

11:12

you will crack it?

11:13

>> Well, I think I think if you slow down

11:18

aging,

11:20

uh it's unlikely that you'll get huge

11:22

gains. What you will get is more and

11:24

more people uh reaching say 100, okay,

11:29

or beyond. I think the uh way that

11:32

people might be able to crack the 120 is

11:35

by this kind of reprogramming

11:38

uh which is you know trying to get cells

11:41

to essentially reverse uh effectively

11:45

reverse their aging uh their biological

11:48

age uh by resetting uh some of these

11:51

clocks. But al although it's been

11:55

demonstrated in animals,

11:57

there are real problems getting it to

12:00

work uh in humans.

12:02

>> Why?

12:03

>> Because you know the way that they

12:06

introduce it in animals is either they

12:08

have transgenic mice which turn these

12:11

genes on or off. And by the way, we

12:13

don't know if these genes are really

12:15

safe over the long run. Some of them are

12:17

anko genes for example which can cause

12:19

cancer. Uh [snorts]

12:21

the other other way to do it is by

12:24

packaging these genes inside a viral

12:27

shell.

12:29

These are called adnoviral vectors and

12:32

then you introduce them. Now the problem

12:34

is that these genes have to go into all

12:37

of the cells in the tissues of interest

12:40

and do it sort of uniformly.

12:43

And all the evidence says that for

12:45

example when they target a pancreas only

12:48

some cells you know some clusters of

12:50

cells in the pancreas are reprogrammed

12:53

and other cells are not reprogrammed.

12:55

Okay. Now in mice this still causes some

13:00

benefit. It still produces some benefit

13:03

but you can see if you want to do it in

13:05

humans you have to be able to do it in a

13:08

much better controlled

13:10

uh and safe way you know. So I I don't

13:13

think I think there's a lot of

13:15

excitement and there's a lot of hype. I

13:18

personally don't think it's around the

13:20

corner as far as humans are concerned.

13:23

And we also don't know for example in

13:25

mice it didn't actually increase the

13:28

longevity of the mice. You know these

13:30

reprogrammed mice they they just older

13:33

mice looked healthier uh by various

13:36

criteria than younger mice but it didn't

13:39

increase their lifespan. different

13:41

organs age at different rates. Uh what

13:43

organ what organs age uh the quickest?

13:47

>> I I think it would vary quite a lot

13:49

depending on the person. You know, you

13:52

could imagine for example, if somebody's

13:53

a heavy smoker, then maybe their lungs

13:55

are aging faster than or somebody's a

13:58

heavy drinker, maybe their liver ages

14:00

faster. I just don't know. uh I I think

14:03

there the one of the more interesting

14:05

papers on it simply showed that if you

14:08

apply most standard markers then

14:12

different organs in in people were had

14:14

different biological ages.

14:16

>> Talking of these markers these hallmarks

14:18

of aging

14:20

um

14:22

what what are the what are the most

14:23

important ones? I think you you

14:25

typically talk about 12 of them but what

14:27

are the most important ones?

14:28

>> I don't think you can say one is more

14:30

important than the other. my as a

14:32

molecular biologist I think you know

14:35

modific damage or modification to DNA is

14:38

fundamental and and really drives a lot

14:42

of the rest. Uh however they're all

14:45

important in their own uh frame. For

14:48

example, damage to mitochondria is is a

14:51

thing in itself and you know loss of

14:54

stem cells is is is a factor in itself.

14:58

Of course, you could say underlying it

15:00

all, maybe the primary cause is is

15:03

damage to our uh DNA and and the

15:06

response to that DNA damage.

15:08

>> How is AI changing the pace of

15:11

discovery?

15:11

>> I think AI uh is very very good at

15:15

recognizing patterns in large data. And

15:19

so for example in my field of structural

15:22

biology uh it has really revolutionized

15:25

the ability to predict structures just

15:28

from the sequence uh that you can get

15:31

from just sequencing the gene for

15:33

example and u but

15:37

I think with aging aging is a complex

15:41

multiffactorial process it's not just

15:44

one thing I mean I mentioned DNA damage

15:46

that's not the only thing you know There

15:48

are all sorts of things that that are

15:51

interconnected

15:52

and how to make sense of that uh is not

15:56

clear and what sort of data you would

15:58

feed uh to AI to train it uh is also uh

16:03

not clear. However,

16:06

what I can say is that AI has been

16:09

advancing so dramatically that it's hard

16:12

to predict anything about AI. What are

16:15

the kind of things you can do now in

16:16

your lab which you couldn't do?

16:18

>> Well, I I mentioned for example you

16:20

could predict structures. Uh another

16:22

thing uh that you could use it for is

16:25

for looking for patterns in genes. For

16:27

example, one obvious thing is if you

16:30

sequenced lots of centinarians,

16:33

you could then ask AI to look at the

16:36

genomes and ask does any pattern emerge

16:40

here? You know that makes sense. For

16:42

example,

16:43

>> Deosabis who won um the Nobel Prize for

16:47

AFold he uh predicts that within 10 to

16:50

15 years there won't be any illnesses

16:53

left.

16:54

>> Any what?

16:55

>> That there won't be any illnesses left.

16:57

>> Yes, I know De I I actually I actually

17:00

know Deis quite well and in fact he

17:04

asked me to be on the advisory board of

17:06

one of his companies, Isomorphic Labs

17:08

and I I think he's a he's a brilliant

17:10

guy. However, I would say on this in

17:13

this case maybe he's being a bit

17:16

overoptimistic and and the reason I say

17:18

that is not because AI won't give us

17:22

clues about you know potential drugs or

17:26

even causes for example uh of diseases.

17:30

But I think going from there to having

17:32

treatments is a complicated process and

17:36

it doesn't happen in the digital world.

17:38

It happens in real people. You have to

17:40

have real medicines, real, you know,

17:43

which you make. So all of that stuff is

17:44

in the analog world and I think that is

17:49

going to take longer.

17:50

>> Do the tech people just think that uh

17:54

life is a software that can be hacked.

17:56

>> Yes, I think I think they have that bias

17:59

whether it's conscious or not. uh they

18:02

do have the bias of looking at the

18:04

entire world as if it's a software

18:07

problem

18:08

>> and the and the world is not digital the

18:10

world is analog and uh I think they

18:14

simply don't

18:16

want to want to confront that

18:19

>> why is there suddenly so much money

18:21

going into longevity research like tens

18:23

and tens of billions

18:24

>> I think there are two reasons one is the

18:26

one you pointed out about for example

18:28

about Japan which is true of all

18:30

societies

18:31

All societies are getting older and

18:34

governments and you know health agencies

18:37

are extremely worried. How do we deal

18:40

with societies where huge fraction of

18:42

the population is quite old and there's

18:45

a smaller and smaller fraction of the

18:48

population that's of working age that

18:49

can support them. Okay. So the one

18:53

solution is to try to put money into

18:55

aging research and this is the the goal

18:59

of this is not what you described

19:01

earlier of living for a very long time

19:04

but rather to make your life health as

19:06

healthy as possible but not necessarily

19:09

extending life but more increasing

19:11

health span rather than lifespan. Okay,

19:14

the fraction of life you're healthy.

19:16

That's one reason and that's a very

19:19

widespread reason everybody will sign up

19:22

to it. Okay, but the other reason is

19:26

that there is a group of people who just

19:30

have these grandiose visions. Okay, and

19:33

it's all based on the fact that they

19:34

made billions of dollars in their 20s

19:38

before they were mature. and they simply

19:41

think that everything is just going to

19:43

go their way. And these people don't

19:45

want to die. Okay? I mean,

19:47

>> why why don't they want to die?

19:49

>> Well, they love their lives. They like

19:51

the feeling of control. Uh they think,

19:53

"Oh, we solved the problem of of uh

19:56

payment transactions. So, we should be

19:58

able to solve death."

19:59

>> Why are they all men? I I do think that,

20:01

you know, they're all middle-aged men,

20:03

often married to younger women, by the

20:05

way, which is a strong incentive to want

20:07

to live [laughter] longer, but but I

20:11

should say, um, maybe it's some male

20:14

thing, you know, of wanting control and

20:17

so on. You're right, you know, and and I

20:19

do point out in the book that they're

20:20

mostly middle-aged men.

20:22

>> Tell me tell me a bit more about these

20:23

men. What do they have in what more do

20:24

they have in common?

20:25

>> They they like control. They like power.

20:30

uh they like uh obviously they like

20:33

wealth uh and so they're used to having

20:36

everything their their way. You know if

20:38

they want to buy an island they can buy

20:40

an island. If they want to buy off a

20:42

government sure they can fund some

20:45

politicians campaigns and then you know

20:47

give them uh money and then you know

20:49

suddenly the regulations disappear.

20:52

Okay. So I excuse me for being a bit

20:54

cynical but you can see this in

20:56

operation in today in the US right so um

21:01

I think I think they're used to that

21:05

kind of power and they also have these

21:07

grandio visions you know they feel like

21:10

we're the only intelligent species in

21:12

the universe or maybe and therefore we

21:14

need to populate the universe and they

21:18

there's a there's a fantastic book by

21:20

Adam Becker called uh more everything

21:24

forever and it's about these people who

21:27

just want more of everything and they

21:29

want to conquer space, galaxies, etc.

21:33

But I don't know if they really mean it

21:36

or if they're saying that so that it

21:39

sounds like a noble cause. Okay. And the

21:42

real reason is they simply want more

21:44

power and they don't want to die.

21:46

>> Now, one of these um uh Bezos backed

21:49

ventures is called Altos Labs, right? uh

21:52

$5 billion, a whole bunch of Nobel

21:55

winners.

21:56

>> I should say that the one of the driving

21:57

forces behind it was actually Yuri

22:00

Milner, who is another tech billionaire.

22:02

>> Yeah.

22:03

>> Yeah. Yeah. What are they betting on?

22:05

>> I I think they Well, you know,

22:08

officially their stance is that they

22:11

don't they're not interested in

22:12

extending life, but they want to extend

22:15

health. And in fact, Rick Clausner,

22:18

[clears throat] I was at the opening of

22:19

the Altos Lunch in Cambridge, and Rick

22:22

Clausner, who's, you know, their chief

22:25

scientist, said, um, look, our goal is

22:30

not for people to live forever. Our goal

22:33

is for everybody to die young after a

22:36

long time.

22:38

Okay? So, my my immediate reaction was,

22:41

if somebody is young, why would they

22:43

suddenly die, you know? I mean, this is

22:46

a a little bit of a paradox. You're

22:48

saying, "I'm going to keep everybody

22:49

healthy, and then suddenly they're going

22:51

to drop dead." Doesn't seem likely to

22:53

me. I think what you'll end up doing is

22:56

postpone that, you know, slow decay and

23:00

decline uh to a later stage in life. Uh

23:04

but anyway, uh that that's a a point of

23:07

that's debatable, but that's their

23:10

stated goal. M

23:11

>> but I have a feeling the people who are

23:13

funding it

23:15

are interested in two things. One is

23:17

they think there's a lot of money in

23:18

aging and so you know if you hire the

23:21

best scientists you which they did some

23:25

of the top scientists in the field uh

23:27

were went to Altos because of the

23:30

resources and the salary offered was far

23:32

better than anything you could get in

23:35

academia and and so uh they're their bet

23:39

is if we hire some top scientists they

23:42

will come up with useful stuff that then

23:44

we can monetize eyes in the longevity uh

23:49

business. And so that's a a clear, you

23:53

know, standard,

23:55

you know, investment strategy. But the

23:58

other strategy is deep down they think,

23:59

well, maybe these guys will crack the

24:01

problem and, you know, maybe we'll end

24:04

up uh living not forever, but maybe a

24:08

much longer time.

24:09

>> We have another got a [clears throat]

24:11

few other players who tried to crack it.

24:12

Kico, New Liit, Brian Armstrong, Brian

24:16

Johnson.

24:18

What are your reflections?

24:19

>> I I I mean, I do know of Brian Johnson,

24:22

who's another tech billionaire who

24:23

spends $2 million a year uh apparently

24:27

on uh his own longevity. He monitors his

24:31

aging. He does all sorts of treatments

24:34

and so on. And you know, he seems a

24:37

pleasant enough guy from watching his

24:39

interviews, you know, and I I think it's

24:41

fine if he does that. And uh he looks

24:43

pretty young for a guy in his late 40s.

24:46

Uh but my son is almost 50 and he looks

24:48

just as young without any of those

24:51

longevity treatments. So, [laughter] so

24:54

I, you know, the trouble of Brian

24:56

Johnson is no control experiment. is

24:57

it's one guy who's mixing up all sorts

25:00

of different things and then how do you

25:03

even judge whether something is working

25:05

or not you know in one person when you

25:07

mix everything up?

25:08

>> Let's move um tax. So stem cells kind of

25:11

deserve their own uh chapter here. Um

25:14

you say in your book that an 80year-old

25:16

has

25:18

the 200s

25:20

uh amount of stem cells compared to a

25:22

newborn.

25:24

Um

25:26

now what are the genuine breakthroughs

25:29

in this area?

25:31

>> Well the the the big breakthrough in

25:33

stem cell research will come from

25:37

reprogramming.

25:38

Okay. So if they can

25:42

implement reprogramming safely in humans

25:46

and and you know demonstrate first of

25:48

all they need to do a lot more research

25:50

on animals before

25:52

>> it has worked in mice right

25:53

>> it has worked in mice but remember it's

25:56

very limited experiment and even in mice

25:59

the reprogramming is highly

26:02

heterogeneous that is even in the same

26:04

organ there clusters of cells that get

26:06

reprogrammed other cells don't get

26:08

reprogrammed Okay. Uh there's one

26:11

interesting experiment that's being done

26:14

in Boston which is about uh trying to

26:18

restore

26:19

um you know regeneration of tissue

26:22

trying to regenerate eye tissue by

26:25

injecting these factors directly into

26:28

the eye. [snorts] And uh maybe this can

26:31

restore damaged or aging tissue like you

26:35

know many diseases are in old age cause

26:39

retinal degeneration which can lead to

26:41

blindness. So uh and that's actually

26:44

been approved for clinical trials. But

26:47

again you know many things that work in

26:50

mice fail in clinical trials. I mean

26:54

that's almost the norm. And so you you

26:57

have to you have to simply wait and see

27:00

what happens.

27:00

>> So hundreds of clinics already sell stem

27:03

cell injections.

27:04

>> Oh well

27:07

I think you know people for example when

27:09

scientists found out that you know if

27:11

you connected an animal old and young

27:14

rat and exchanged their blood supply the

27:18

old animal seemed to benefit from the

27:20

blood of the young animal. And

27:22

immediately there were companies that

27:24

were starting to sell young blood, okay,

27:26

from to, you know, from they would get

27:29

blood from young donors and sell them at

27:31

a huge markup to rich uh old men.

27:34

>> Do you think uh uh there is something to

27:36

it or is it just

27:37

>> No, I I I I'm highly skeptical.

27:40

>> Okay. Another area is uh

27:42

cryopreservation. So basically you

27:44

freeze yourself and hopefully you wake

27:46

up later. Yeah, this this is currently I

27:50

would say in the realm of science

27:51

fiction. Uh it's not because

27:53

cryopreservation itself has no basis.

27:57

For example, we can freeze eggs. We can

28:00

freeze even embryos. We can certainly

28:02

freeze, you know, lots of even small

28:04

larve uh of of worms and so on. So, so

28:08

there are many things we can freeze and

28:11

the the method of freezing depends on

28:15

cooling them to very low temperature

28:17

like liquid nitrogen temperature without

28:19

the water freezing into ice. Okay?

28:22

Because if it freezes into ice, ice is

28:25

expands compared to water. So, it

28:27

destroys all the tissue around it.

28:29

That's why you know if you freeze your

28:31

strawberries in your freezer and you

28:33

thaw them again, they don't look like

28:34

fresh strawberries. Okay? So um the the

28:38

the reason you can do it with small

28:41

things is because you can transfer the

28:44

heat fast away from it fast enough

28:47

before the water has a chance to form

28:49

ice crystals. So you get essentially uh

28:53

you know a a sort of native state.

28:57

Now nobody has been able to freeze even

29:01

a small animal like a mouse. Okay? And

29:04

there was some report about a mouse

29:05

brain being frozen. Then when I looked

29:08

at it, it's not a whole not even a whole

29:10

mouse brain. It's only a a section of a

29:12

mouse brain. A thin section of a mouse

29:14

brain they've been able to freeze. Okay?

29:17

So I would say to these people, when you

29:20

can freeze a mouse and thaw it so that

29:23

it can run around again, uh then come

29:25

and talk to me. I'll be interested.

29:27

Until then, it's just, you know, I I I

29:30

think of it as nonsense. In the

29:32

meantime, if we gave you $3 billion to

29:36

conduct research into whatever you

29:38

wanted, where would you where would you

29:40

have put that money? What's the most

29:42

promising part

29:43

>> in for you mean for aging research?

29:45

>> Yeah.

29:46

>> Okay. I would put it into three or four

29:48

areas. One is we know that caloric

29:51

restriction

29:53

uh does help

29:55

>> with aging. Okay. And and it's been this

29:58

has been true in many species. It has

30:00

some consequences which are not always

30:02

good but maybe you can separate those.

30:05

So I would put money into caloric

30:08

restriction pathways. That to me is the

30:11

most promising short-term goal. Okay.

30:15

Then you know we talked about old and

30:17

young blood. Well one possibility is to

30:20

try to ask what is in old blood and

30:22

what's in young blood. what are the

30:24

differences and what how do they promote

30:27

aging or prevent aging you know so uh so

30:31

that's another area I I talked about

30:34

cells that sense damage and go into into

30:37

this state called scinessence and that's

30:40

a natural process that's very useful uh

30:43

throughout our lives but as we get older

30:46

the the number of scinsesscent cells

30:49

increases too much beyond our body's

30:53

ability ability to clear them. And so

30:56

there are efforts to target scinesscent

30:58

cells for destruction. Again, it's a

31:01

question of being able to do it in the

31:03

right amount and you know and and not

31:06

damage all our other cells. Uh so that's

31:09

another promising area. And then the

31:11

fourth is the part that we talked about

31:13

which is cellular reprogramming. And I

31:16

think that is perhaps one of the more

31:19

exciting long-term goals. and and I

31:22

think you know that's another area where

31:26

uh you could you could you know do a lot

31:28

of useful research

31:30

>> now in the meantime um we just want some

31:33

more healthy years and so uh where do

31:37

where do we start

31:39

>> well you know caloric restriction

31:41

pathways suggest an obvious answer one

31:44

is

31:44

>> so this is basically just being hungry

31:47

>> no I don't think you need to be hungry I

31:49

I you're right that People on a truly

31:51

caloricrestricted diet, they're hungry

31:54

all the time.

31:55

>> Which is why I don't do it.

31:56

>> No. And nor do I. Okay. But you can eat

31:59

moderately and you can eat, you can try

32:03

to not be obese. You can control your

32:05

weight. By the way, GLP1 drugs have now

32:09

shown all kinds of effects, not just for

32:11

preventing diabetes or for extreme

32:13

obesity.

32:14

>> And so they could be investigated

32:16

further as well. And they

32:18

>> do you think they'll extend do you think

32:19

they'll extend lifetime?

32:20

>> They they might uh I don't know about

32:23

extending life but they might make it

32:25

old age healthier.

32:27

>> Uh but but they have consequences. For

32:29

example, you have muscle loss, you have

32:31

other side effects. So people need to

32:34

figure out how to use them safely. You

32:37

know, if you're going to try to give it

32:38

to healthy people, you have to try to

32:40

make it uh safer. But anyway, uh you so

32:44

I would say caloric restriction suggests

32:46

an obvious answer which is you know

32:49

don't overeat. Why does it work?

32:51

>> It works because it turns on pathways

32:56

that are involved in recycling

33:00

uh you know defective uh molecules and

33:05

defective organels uh and generally

33:08

speak and affects your protein

33:10

synthesis. So you don't make you know

33:12

misfolded proteins. So there there are

33:15

lots of thing there are lots of things

33:17

it affects in our metabolism

33:20

uh that benefit us as we age. The the

33:23

other thing I I I should mention is

33:25

sleep.

33:26

>> Yeah. because a lot of recycling and

33:28

repair happens in our sleep cycle and

33:32

people underestimate the importance of

33:34

sleep and uh that's another uh you know

33:38

very important uh aspect and of course

33:41

the third one is exercise and exercise

33:44

you know we talked about rejuvenation

33:46

and regeneration of tissues and so on

33:48

and exercise actually stimulates that

33:51

>> let's just sleep first how much do you

33:52

sleep

33:53

>> I try to get about eight hours of sleep

33:55

a day.

33:56

>> And you know, if I get less than 7

33:59

hours, I don't function very well.

34:01

>> There is this saying uh when you're

34:03

young, you sneak out of your bedroom to

34:05

go to parties, and when you get older,

34:07

you sneak out of the parties to get back

34:08

to bed. Why

34:10

>> I unfortunately [laughter] I was I was I

34:13

was a sleepolic, if you like, even when

34:16

I was young, you know. So maybe

34:18

>> why why do we appre appreciate sleep

34:20

more when we get older?

34:21

>> I I don't know. Maybe maybe, you know,

34:24

we're just not as energetic and not as

34:27

you know, we don't have the same stamina

34:30

as we did when we were when we were

34:32

young. But but as I pointed out, you

34:34

know, uh not only I but even my son and

34:38

and I I believe also my grandson, uh you

34:42

know, we all like our sleep. You know,

34:45

I'm not sure we're all night party

34:46

animals.

34:47

>> No, sleep is beautiful. What about

34:49

exercise? How much do you exercise? I

34:51

try to ex you know firstly I I ride my

34:54

bicycle about uh a few kilometers each

34:57

way uh to work every day but apart from

35:00

that I go to the gym and I do a

35:03

combination of weight training and uh

35:07

cardio uh I don't my knee is not great I

35:10

used to be a runner but now I uh mostly

35:13

do a an elliptical cross trainer uh

35:17

which as somebody from Norway you'll

35:18

you'll appreciate it sort of mimics

35:20

mimics crosscountry skiing, you know,

35:22

>> much better for much better for the

35:24

joints.

35:24

>> Yeah.

35:25

>> Uh but talking about Norway, what about

35:27

ice bars and cold plunges and zonas?

35:30

>> You know, the trouble with all of these

35:32

things is they come from one or two

35:35

observations which may or may not be

35:37

even validated

35:40

and there's no control experiment. Okay,

35:43

I would be very very skeptical uh of

35:47

those sorts of uh treatments. I I doubt

35:49

that they do much to be honest.

35:51

>> Well, hey, they do a lot for me. I did

35:53

both both an ice bath and um and sauna

35:56

this morning and it makes me feel uh

35:58

>> Oh, if it makes Okay, so let me let me

36:01

address that. Anything that makes you

36:03

feel good is probably okay, probably

36:05

good for you at some at some level

36:08

because a lot of it a lot of aging is

36:10

related to stress. you know there's I

36:13

I'm sure people who are happy probably

36:17

uh you know have less stress and less

36:20

you know damage to their systems and so

36:22

on. I mean up to a point you know if you

36:25

like drinking I wouldn't say you know go

36:27

go out and get drunk every day. I I'm

36:29

not sure that's a good idea but but if

36:31

you you know if a cold plunge in a sauna

36:33

makes you feel good that's great you

36:35

know you should do it.

36:37

>> Let's move to to the ethics. Um, now if

36:40

we could double the the lifespan

36:43

tomorrow, do we do we actually want to?

36:45

>> I think it would cause huge changes in

36:48

society, not all of which will be good

36:50

for society. Uh, for one thing, you

36:54

know, changes in society uh require

36:58

turnovers of generations. Old

37:00

generations don't, you know, older

37:02

generations don't voluntarily change

37:04

society. Often change is driven by the

37:07

young. And so um so you you you might

37:11

end up with a very stagnant society. The

37:14

other is that as old people as people

37:17

get older they accumulate wealth,

37:19

influence and power. And of course these

37:21

three things go together. And so you

37:24

will have the same group of people

37:26

controlling society without turnover.

37:29

And that is not a recipe for for for

37:34

good society. you know because people

37:36

who are entrenched in power have no

37:38

reason to change and and you know may

37:41

not act in the best interests of

37:43

everybody and I should point out that if

37:47

you look at great discoveries in science

37:49

and mathematics they're almost all done

37:51

by young people okay and you know people

37:55

in their 40s or younger and um you know

37:59

yes there are a few exceptions here and

38:01

there but even those people often did

38:04

great work when they were young. It's

38:06

just that they've uh continued. And

38:09

interestingly, you know, Ishiguro, the

38:12

famous uh novelist, pointed out that

38:15

even in literature, this is true that

38:18

you know, generally speaking, people who

38:21

are younger uh you know, t people tend

38:24

to write their greatest works when

38:26

they're younger. And one example he gave

38:29

was Toltoy. You know, Warren Peace was

38:32

written when he was in his 30s. you

38:33

know, that's supposed to be this big,

38:35

profound novel and yet was not written

38:38

by an old man. So, you know, I I I

38:42

wonder what it'll do to,

38:46

you know, society generally if we have

38:49

everybody living for a very long time

38:50

and especially combined with drop in

38:53

fertility rates where uh you're not

38:56

you're not replacing them with young.

38:57

>> During COVID, we treated the old people

38:59

first. Was that wrong? Well, it wasn't

39:01

wrong because they were by far at the

39:04

greatest risk. So, uh, you know, the the

39:08

likelihood of dying of COVID doubled

39:11

every eight years of life, you know,

39:13

roughly speaking. And so, an 80-year-old

39:17

was many many times more likely to die

39:19

than say a 40year-old or a 30-year-old.

39:22

So I I I think it it if you wanted to

39:25

save lives, you know, that was not not

39:28

not a bad thing to do.

39:30

>> The rich people already live uh you know

39:33

a decade and even some places more than

39:36

that longer than the poor.

39:37

>> Yeah. 15 years in the US and about 10

39:40

years in the UK.

39:41

>> So what reflections do you have around

39:45

that or or extending it further for rich

39:48

people? I I I think it it it creates a

39:50

serious problem especially if let's say

39:53

you have advances in in aging research

39:57

and you have treatments that are highly

40:00

sophisticated and expensive. Uh then you

40:04

can imagine a two-tier society where

40:07

rich people can get all of the latest

40:09

and fancy treatments and will live even

40:12

longer than they do now. And so the

40:15

disparity in power because as I pointed

40:18

out people accumulate power and wealth

40:21

will be even more and moreover their

40:25

children will also be at an advantage.

40:28

So you you may end up creating a

40:30

multi-tiered society, you know, or at

40:32

least a two-tiered society where, you

40:35

know, there's one rule for the very rich

40:38

and it's not just even wealth, but it's

40:40

even years of life and then another uh

40:44

situation for uh the rest of society and

40:47

especially for the poor.

40:49

>> Mickey, let's uh uh

40:51

talk a bit about you here at the end.

40:53

You trained you grew up in India. you

40:54

trained as a physicist and then switched

40:57

to biology. Why why is physics uh a good

41:01

place to start?

41:02

>> Well, I'm not sure

41:03

>> or or is it?

41:04

>> I you know, I think it uh well, it

41:06

didn't hurt me, but I'm not sure it's

41:08

necessary. Uh except that one thing

41:11

physics does is it trains you very well

41:14

in mathematics and in quantitative

41:16

thinking. Uh and that can be useful. But

41:20

I can tell you physicists who be try to

41:23

become biologists without

41:26

really becoming biologists but staying

41:28

as physicists they don't tend to do very

41:30

well. Okay. Uh the best physicists

41:34

best people who have gone from physics

41:36

to biology are people who stopped being

41:39

physicists and really learned how to

41:41

think like biologists because biology

41:44

involves a different way of thinking.

41:47

it's a different scale and different

41:48

kinds of problems. uh for example

41:51

physicists almost there's no such I

41:54

never heard of a control experiment in

41:56

physics because the experiment itself is

41:58

designed so that you know it it's

42:02

designed to be extremely simple and

42:04

answer a particular question and in

42:07

biology the system is so messy that you

42:10

you have to do control experiments you

42:12

know and and so that's one one concrete

42:17

example but there are many other ways

42:18

and for example everything in biology

42:21

requires thinking in evolutionary terms

42:24

and that's doesn't come quite naturally.

42:27

Physics is a generally a highly

42:29

reductionist

42:30

uh you know science although now you

42:33

know many physicists are going into

42:35

complex systems and so on but but

42:38

traditionally it has been a highly

42:39

reductionist science. So I think there

42:42

are cultural differences and you have to

42:44

bridge those differences if you want to

42:46

succeed in making that transition. Do

42:49

you think with the advent of AI that

42:52

having a broad curriculum uh is more or

42:55

less an advantage?

42:58

>> My view is having a broad curriculum is

43:00

always an advantage because it really

43:02

gives you an understanding of the

43:05

different areas of science, different

43:07

ways of thinking and so on. And uh one

43:11

worry I have is that we are going to uh

43:14

simply delegate everything to AI which

43:18

would be a recipe for making humanity

43:21

stupider. Uh I think and more ignorant

43:24

and I think what we really should be

43:27

doing is is leveraging AI so that it's a

43:31

another powerful tool in our armory. I

43:35

mean computation was a tool uh you know

43:38

all sorts of modern robotics is a tool

43:42

uh you know we have all sorts of tools

43:44

chemical tools you know biological tools

43:47

and and I I think we should think of AI

43:49

as another uh powerful tool.

43:52

>> What did you learn as a president at the

43:54

Royal Society?

43:55

>> Well I learned a lot of things. One is

43:57

how to convey science to the general

43:59

public. how to convey the importance of

44:02

science to not only the public but to

44:05

the government. And you know I became

44:08

president at a very particular moment in

44:11

British history when it had voted to

44:13

leave the EU and then towards the end of

44:16

my term we had the global pandemic. uh

44:19

and so you know I had to deal with uh

44:22

really quite serious issues as president

44:25

and I think uh the fact that I was an

44:28

American uh citizen who had come to

44:31

Britain and I didn't have a I didn't

44:34

grow up here and didn't have a network

44:36

of people here I I thought that might

44:38

have been a disadvantage but on the

44:40

other hand it made me viewed as somebody

44:43

with no axe to grind you know somebody

44:45

who you know was perhaps an out

44:48

something of an outsider but therefore

44:50

objective. Uh so it it may have helped

44:53

me as much as it hurt me.

44:55

>> Why is uh music so important in your

44:57

life? And uh your son is a professional

45:00

chist and a music professor as well. So

45:03

he

45:04

>> Yes, you you you've clear you've clearly

45:06

done some homework on me [laughter]

45:08

anyway. No, we I've always enjoyed music

45:11

and I think you know music is one of

45:13

those universal uh things. I don't quite

45:16

understand.

45:18

You know, Steven Pinker in his book sort

45:21

of dismissed music. You know, he thought

45:23

it was a just an artifact of no

45:26

evolutionary significance. I think he's

45:27

wrong. And I think music is a a

45:31

demonstration of very very high

45:34

cognitive ability. And so you can see

45:37

how evolutionarily it's it's important.

45:41

uh but more than that I think music

45:44

really we have evolved to so that music

45:47

has some deep uh you know emotional and

45:51

physiological triggers in us and you you

45:54

know you can easily change a person's

45:56

mood with music and affect their

45:58

physiology so so I think there's

46:01

something profound about music

46:03

>> do you think it makes you live longer

46:06

>> I don't know but it can certainly make

46:08

your life the life you have far more

46:10

pleasurable. So,

46:12

>> do you think gratitude makes you live

46:14

longer?

46:15

>> I don't know if I don't know if any of

46:17

these things particularly make you live

46:19

longer. I I think, you know, some things

46:23

you you do because they're worth doing,

46:25

not just because everything everything

46:27

is not about living longer. It's about

46:30

enjoying life while you have it, right?

46:33

>> Are you afraid of dying? I think we all

46:36

are at at some level but I think you

46:38

know I mean my father and my

46:40

brother-in-law both died in the last

46:42

year and a half and my father was almost

46:45

99 and I would say you know he faced you

46:48

know when he he was told look now you

46:51

only have a few days left uh you know he

46:54

was a little bit sad that it was going

46:56

to be over but I think he took it

46:58

reasonably well and and my

47:00

brother-in-law you know he suffered from

47:04

sudden diagnosis of pancreatic cancer

47:06

but really you know was very

47:10

measured and you know sort of rational

47:13

about it. So I so I hope if you know not

47:17

if but when my time comes that I'll face

47:19

it with the same kind of you know

47:22

equinimity or rationality that that I

47:25

saw in these people.

47:26

>> You had a Freudian slip there and said

47:29

you know if you die do you do you

47:31

believe in afterlife? I no I I I I don't

47:35

but uh No, I meant I meant when when I

47:37

died. I I don't know if it was a

47:39

Freudian slip. It's just it's been uh

47:42

tremendous to uh speak with you. What a

47:45

what an incredible experience. A big

47:47

thank you for taking the time.

47:48

>> Thank you very much for having me.

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