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Could we be looking at age the wrong way? Nor

0:59

do people age the same.

1:01

And so biological age is

1:03

what we think could capture

1:05

health. It's Thursday, May 30th,

1:07

and you're listening to Science Friday. I'm

1:10

sci-fi producer Dee Peter Schmidt. We've

1:12

all seen how some people seem to age more

1:14

rapidly than others, even if they're at the same

1:17

chronological age. So why is that? Well,

1:20

there's been a growing field of medicine dedicated

1:22

to better understanding how we age. Here's

1:24

Ira with a researcher who's trying to find out more.

1:27

Joining me now to talk about

1:29

this is my guest, Dr. Aditi

1:31

Gurka, assistant professor of geriatric medicine

1:34

at the University of Pittsburgh School

1:36

of Medicine in Pittsburgh, PA. Welcome

1:38

to Science Friday. Thank you so much

1:40

for having me on the show, Ira. It's

1:43

nice to have you. Now, I understand

1:45

that you got into this topic of

1:47

biological aging by watching your grandparents age.

1:49

Is that right? You know, in

1:51

India, we grew up in like sort of a

1:53

joint family. So my grandparents

1:55

actually stayed home with us, which was

1:58

great. I loved having my grandparents. grandparents

2:00

around but as they were getting

2:02

older it was very easy to

2:04

tell that my

2:06

grandfather who aged, you know,

2:10

very gracefully and naturally did

2:12

almost everything functionally till

2:14

the end of life You

2:16

know did my homework with me

2:18

told me grandpa jokes basically and

2:21

on the other hand my grandmother You

2:23

know her last 15 years of her life She

2:26

could really not make it out of bed.

2:29

She had dementia really could not even remember

2:31

who I was So

2:33

at a very young age, I started wondering

2:35

why you know two people in the same

2:38

household But seem to

2:40

age very differently and

2:42

that's kind of what captured my interest

2:44

very early on Well, is

2:46

there is there a common definition

2:48

of what aging or getting old

2:51

is? That's the million dollar question

2:54

Right. We all look at chronological age

2:57

Which serves as a conventional marker of

2:59

course That's the age

3:01

that we have on our license and on

3:03

our passports However,

3:06

just like you captured it in your introduction No,

3:10

two people aged the same and

3:12

so biological age is what we

3:15

think could capture Health

3:18

and so how healthy we are how

3:20

much wear and tear our bodies have

3:22

gone through Basically telling us

3:24

about how we feel And

3:27

it does so by capturing

3:29

the interplay of multiple factors

3:31

including our genetics our

3:33

environment What did we eat last

3:35

night? Right? Or did we

3:37

even get some exercise during the day? So

3:40

biological aging is sort of like a quality

3:42

of life thing. Correct. Correct

3:44

Much more difficult to measure.

3:46

Yeah, and it's not something that

3:49

you can determine by just looking

3:51

at a person Unfortunately

3:53

not maybe we can when a person's

3:55

70 75 maybe right But

4:01

the goal would be to capture

4:03

biological age very early on

4:05

so that we can predict whether one's

4:07

going to be a healthy ager or

4:09

a rapid ager so that we

4:11

can take the right steps to

4:13

change that. Now, you recently

4:16

made a breakthrough in biological

4:18

markers to determine

4:20

aging. Tell us what you found there.

4:23

Well, thank you, first of all, for calling it a

4:25

breakthrough. As a scientist,

4:27

I'm always looking

4:29

at my work and I think there's

4:31

so much to do. Right. But

4:34

yes, we are really excited about this

4:37

new study that we did. Some

4:40

of us in the field, including our

4:42

lab, but many others had identified that

4:44

as we age, we

4:46

all accumulate certain cells,

4:49

dysregulated cells in our body that

4:52

in popular literature get called zombie

4:54

cells. And in

4:56

science, they call it senescent cells.

5:00

So these cells accumulate in all of us

5:02

and seem to be playing a major role

5:05

in disease. Really? Yeah.

5:08

And when I was a postdoc,

5:10

seems like ages ago now, we

5:13

had worked with multiple teams,

5:15

including the Mayo Clinic and

5:17

the Scripps Research Institute, to

5:19

look for drugs that could

5:22

eliminate such dysfunctional cells, at

5:25

least in animal models. And what

5:27

was really exciting was when we

5:29

could get rid of

5:31

these zombie cells, at least

5:33

the mice did much better. They aged

5:36

much more healthy. And that was sort

5:38

of like, oh, wow,

5:40

can we start a

5:43

process where we can delay biological

5:45

aging? Right. So in the study,

5:48

what we did was we looked

5:50

at markers of this senescence, but

5:53

we also integrated it

5:56

with another marker called

5:58

metabolites. Our

6:00

body releases unique small molecules, chemical

6:02

fingerprints, if you will, all

6:05

the time. And these are

6:08

substrates, intermediates, and byproducts of

6:10

our everyday metabolism. What's

6:13

great about metabolites are they're circulating

6:15

in all of us and can

6:17

really tell us about how we

6:19

feel. They tell us about our

6:21

physical state, our functionality. So

6:24

in this study, for the first time, we

6:26

have integrated two very

6:28

important things, metabolites as

6:30

well as markers of

6:32

senescence together in order

6:34

to capture biological age. And

6:37

so how do you judge what biological

6:39

age is based on these markers? Great,

6:41

great. So what we started out

6:44

was with this cohort where we

6:46

really looked at functional capacity, mostly

6:49

by doing a walk

6:51

test or a gait speed. The

6:53

reason we decided to look at gait

6:55

speed for our initial study was that

6:58

the gait speed has been linked

7:00

to hospital readmissions, linked to

7:02

how we feel, and it

7:04

really captures multiple things going

7:06

on in our bodies, including

7:08

pain, how we are feeling

7:11

on a specific day. So

7:13

all of these things together kind

7:16

of go into gait

7:18

speed and walking abilities. So

7:20

that's kind of what we captured

7:22

in our first study was we

7:24

called biological age as

7:27

healthy agers who could walk

7:29

for about six minutes without

7:31

taking many rest and

7:34

felt really good doing so. There

7:37

was a part of the cohort that

7:39

could not walk for the six minutes

7:42

continuously and needed to take breaks.

7:45

And so that's what we call rapid

7:47

agers. Now, mind you,

7:49

all of these people in

7:52

this cohort were about the age of 65. And

7:55

we kind of set off this

7:58

chronological age. up

8:01

or threshold to kind of really

8:04

capture what's happening with

8:06

age rather than comparing someone

8:08

who's 25 with a 65-year-old. Right.

8:12

So did you find more markers?

8:15

Yeah. In a certain group of people? Tell

8:18

me about that. Yeah. So

8:21

what was exciting was by looking

8:23

at about 1,400 metabolites

8:25

that are circulating in one's

8:28

blood, we could come up

8:30

with a marker of 25 metabolites

8:32

that could distinguish between

8:34

healthy agers and rapid

8:36

agers. Now what are these metabolites?

8:39

Some of these are lipids.

8:42

Some of these are basically

8:45

byproducts of plants, fruits, and

8:47

vegetables that people eat. And

8:50

together, these 25 metabolites could

8:52

tell us who is a

8:54

healthy ager versus someone

8:56

who could be an early or

8:59

rapid ager. So these sounds

9:01

sort of like aging risk factors. Well,

9:04

in this case, that's actually a

9:06

good point. And that's where we

9:08

have now done some more

9:10

work into looking at

9:12

causal factors that could

9:15

really drive biological aging. We

9:18

have come up with two things that we think

9:20

are really exciting and we want to follow through.

9:23

One is how well one's

9:26

mitochondria function. Mitochondria

9:29

are these organelles in all of

9:31

us, most popularly called the powerhouse

9:33

of the cell. This is

9:35

an organelle which is

9:37

very important for metabolism, breaks

9:40

down fatty acids, and

9:42

gives us energy basically. And

9:45

so we find that healthy agers

9:47

seem to have better

9:50

mitochondria, more functional mitochondria

9:52

compared to rapid agers.

9:55

So that's kind of exciting and we

9:57

think that rapid agers instead. they

10:00

cannot use their mitochondria seem to

10:02

break down their fat in other

10:05

places such as another organelle called

10:07

the endoplasmic reticulum or the ER.

10:09

And here we get these byproducts

10:12

that might end up being more

10:14

toxic to health. So

10:16

that's kind of the first thing we are following through.

10:19

The other exciting part was, and

10:21

this is more, I guess, you know, that

10:24

my mom was right, because my

10:26

mom always told me to eat more

10:28

vegetables. And

10:31

one of the metabolites that we found

10:34

in our study really comes from fruits

10:37

and vegetables. And this

10:39

really correlates well with healthy agers.

10:42

So, you know, I think,

10:44

again, everybody, your moms were right, please

10:47

eat your fruits and vegetables. On

10:49

this Radiolab live

10:51

from stage, we take you from a shopping

10:53

mall to

10:55

the dark side of the moon, rewinding back and asking, how

10:57

did we all end up feeling so alone? I say that

11:07

line and I get one of two responses. One is

11:10

this, all of you laughing

11:12

to which I say, wait, how do you feel

11:14

at the end? Mixtapes to the moon. Listen, wherever

11:16

you get podcasts. Well,

11:19

it sounds like you were investigating

11:22

the rapid aging people at 65.

11:24

What about the normal

11:26

quote unquote, aging people? Right. I mean,

11:29

was there a difference there? And then

11:31

I'm going to move on to the

11:33

older people who are still, as I say, playing pickleball at

11:35

80. Correct, correct. So

11:38

in this cohort, we had 200

11:41

people that were, 100

11:43

of them were healthy agers, what

11:46

you called normal, you know, aging.

11:48

So these are the people who

11:50

could play pickleball. They

11:52

didn't need to rest for five minutes.

11:54

They could walk fairly well.

11:56

We had also captured many other

11:58

things, including their memory scores,

12:00

you know, how fast they can get

12:03

in and get out of a chair,

12:05

things like that. And

12:07

these people did really well in these functional

12:09

tests. So just like you said, people who

12:12

can do great, even in their

12:14

80s. Right. And then we

12:16

compared them with the rapid age. So

12:19

comparing these two is

12:21

what gave us this index of

12:24

healthy aging. I see. I

12:27

see. So what about genetics? Because

12:30

there are some people that, you know, like my

12:32

mom lived to just about almost 100. Wow.

12:36

Yes. Thank goodness. And

12:39

you come up with people who's who, you

12:41

know, and we're having an aging population that's

12:43

living a lot older for some people, aren't

12:45

they? Absolutely. I mean, is there something useful

12:47

you can take out of your study for

12:49

that cohort? Absolutely. I mean, I

12:52

think this is why we need to

12:54

look at aging right now. You know,

12:56

we are also viving to much older

12:58

ages than we did 40, 50 years

13:01

ago. So our population demographics

13:05

are changing completely. Now,

13:09

does genetics play a role in

13:11

biological aging? Absolutely. There is

13:13

no question about it. However,

13:16

we think, and several studies

13:18

have looked at this before,

13:21

where they've compared even twins,

13:24

right? So having very similar

13:26

genetics and

13:28

looked at how they age

13:30

and other factors can kind

13:34

of control how one's aging. Even

13:36

in these twin studies, their

13:38

environment, their lifestyle choices, all of

13:40

these made an impact on how

13:42

they were aging, not just their

13:44

genetics. And so that's

13:46

why we decided to look at metabolomics

13:49

because it can arise

13:51

from capturing all of these

13:54

factors, including genetics and lifestyle

13:56

choices. So what are the

13:58

implications of your findings? Are

14:00

you talking about a possible test you

14:03

can take at the doctor's office and look at

14:05

your metabolites and say, oh, you're

14:07

not eating enough vegetables or something like

14:10

that? Yeah, I mean,

14:12

the hope is that, you know, we

14:14

are at very early stages in our study.

14:17

What I'm really looking for in the future

14:19

is, yes, when we do our annual exam,

14:21

can we just do a simple blood test?

14:24

And that can tell us, although

14:26

our chronological age is 40, like

14:29

I am, but my

14:32

biological age is only 30, or

14:36

whether you're heading in the opposite way. And

14:39

by touching your risk to

14:42

be an early ager, you know,

14:44

we can perhaps personalize these

14:46

interventions. Maybe someone has

14:48

a lot more of these senescent cells.

14:52

And so maybe there's an

14:54

intervention of giving senolytics or

14:56

xenotherapeutics, the small molecules that

14:58

can eliminate senescent cells, right?

15:01

Oh, I see. Now on the other

15:03

hand, some medical

15:05

tests are based on how old you

15:08

are. For example, colonoscopies for cancer are

15:10

not prescribed for people 75 or older,

15:12

right? Because

15:14

the risk outweighs the benefits. But if

15:16

your biological age is, let's say, 65,

15:18

even though your chronology is 75, shouldn't

15:22

you still be getting those tests? Correct,

15:24

exactly. I mean, that's the thing

15:27

is we know that, and

15:30

especially now, I'm sure

15:32

you've realized this as well, in the last

15:34

few years, a lot of people in the

15:36

middle age also have started becoming susceptible

15:39

to other cancers, right?

15:42

Yes, yes, absolutely. And so we

15:44

will have to change policies on

15:47

when we have to start testing,

15:49

probably soon. But

15:52

something like that, we kind of need to dig

15:54

deeper into what one's biological age

15:56

is. test,

16:00

your panel, so to speak,

16:02

be available to doctors to use? Great

16:05

question. As a scientist, I'm

16:07

always very careful about, you

16:10

know, making sure that our

16:13

test is going to be sensitive.

16:15

It's really going to pick up

16:17

biological aging, and it's reliable and

16:20

confident, right? Saying that,

16:22

I think there are two main things we

16:24

need to do. One is

16:26

hopefully do a study where

16:29

we can look at already known

16:31

interventions for aging. For example, exercise.

16:34

It's the best known intervention, at least that

16:37

we have currently. So we

16:39

are hoping that we can look at a

16:41

cohort where before and

16:43

after exercise, do we see

16:45

any changes in their biological

16:47

age based on our metabolites?

16:50

And then the second thing we need to do is

16:53

figure out how early on can

16:55

we tell a person is biologically

16:58

aging? Is it in their

17:00

30s? Is it in their 50s? Or

17:03

really, we have to wait until

17:05

their 70s, right? And then

17:07

it doesn't really serve a purpose or maybe

17:10

much of a purpose. Right. So

17:13

I think those two things are important

17:15

questions to address. And we're really working

17:17

towards both of these currently. And if

17:20

we can get that to go,

17:22

then I think I'm really looking

17:24

forward to having this test a

17:27

few years from now. So

17:29

what you're saying is it's very important

17:32

to determine your biological age,

17:34

possibly even early in life,

17:37

and then keep up with it, keep determining it

17:39

as you get older, because

17:42

it's got a great impact. Absolutely.

17:45

Absolutely. Because I think what

17:47

we are doing in medicine

17:49

now is only taking care

17:53

of the symptoms. Once

17:55

we have a disease, that's what

17:57

we are treating. But if we can of

18:00

aging as the

18:03

underlying factor that drives all

18:05

of these diseases and

18:08

if we can really intervene early

18:10

on in life then

18:12

the hope is we don't have to treat

18:15

one disease at a time we can just

18:17

have a healthier life for a longer period

18:19

of time. A lot of what you

18:21

said is really interesting and makes a lot of sense I

18:23

want to thank you for taking time to be with us

18:25

today. Thank you so much for

18:28

having me again Ira. Dr.

18:30

Aditi Gurka, Assistant Professor

18:32

of Geriatric Medicine at

18:34

the University of Pittsburgh School of Medicine in

18:37

Pittsburgh, Pennsylvania. That's all the time we have

18:39

for today lots of folks help make the

18:41

show happen including Kathleen Davis,

18:43

Diana Plaster, Beth Ramey,

18:45

Danielle Johnson. Tomorrow we'll

18:47

be rounding up the top news and science

18:49

this week. I'm sci-fi producer Deepy

18:52

Dershmit. See you then. There's

18:56

a lot going on right

18:58

now mounting economic inequality threats to

19:01

democracy environmental disaster that sour stench

19:03

of chaos in the air.

19:05

I'm Brooke Gladstone host

19:07

of WNYC's On the Media.

19:10

Want to understand the reasons and

19:12

the meanings of the narrative that

19:14

led us here and maybe

19:16

how to head them off at the park? That's

19:19

On the Media's specialty. Take a listen

19:21

wherever you get your podcasts.