How young blood might help reverse aging. Yes, really | Tony Wyss-Coray

Prevoditelj: Dora Ustulica Recezent: Ivan Stamenković

This is a painting from the 16th century from Lucas Cranach the Elder.

Ovo je slika iz 16.stoljeća, Lucas Cranacha starijeg.

It shows the famous Fountain of Youth.

Prikazuje poznatu Fontanu mladosti.

If you drink its water or you bathe in it, you will get health and youth.

Ako popijete vodu iz nje ili se okupate u njoj,dobit ćete zdravlje i mladost.

Every culture, every civilization has dreamed of finding eternal youth.

Svaka kultura, svaka civilizacija je sanjala o pronalasku vječne mladosti.

There are people like Alexander the Great or Ponce De León, the explorer,

Postojali su ljudi, poput Aleksandra Velikog ili Ponce De Leona, istraživača,

who spent much of their life chasing the Fountain of Youth.

koji su proveli većinu svog života u potrazi za Fontanom mladosti.

They didn't find it.

Nisu ju pronašli.

But what if there was something to it?

Ali što ako ima nešto u tome?

What if there was something to this Fountain of Youth?

Što ako ima nešto u Fontani mladosti?

I will share an absolutely amazing development in aging research

Podijelit ću apsolutno nevjerojatan razvoj u istraživanju starenja

that could revolutionize the way we think about aging

koji bi mogao revolucionirati način na koji mislimo o starenju

and how we may treat age-related diseases in the future.

i način na koji bismo u budućnosti mogli tretirati bolesti povezane sa starenjem.

It started with experiments that showed,

Počelo je s eksperimentima koji su pokazali,

in a recent number of studies about growing,

u nedavnim studijama o starenju,

that animals -- old mice -- that share a blood supply with young mice

da se životinje-- stari miševi-- koji dijele zalihu krvi s mladim miševima

can get rejuvenated.

mogu pomladiti.

This is similar to what you might see in humans, in Siamese twins,

To je slično onome što možete vidjeti kod ljudi, kod sijamskih blizanaca,

and I know this sounds a bit creepy.

znam da to zvuči pomalo jezivo.

But what Tom Rando, a stem-cell researcher, reported in 2007,

Ali ono što je Tom Rando, istraživač matičnih stanica, izvijestio 2007.

was that old muscle from a mouse can be rejuvenated

je da stari mišić miša može biti pomlađen,

if it's exposed to young blood through common circulation.

ako se izloži mladoj krvi zajedničkim optokom.

This was reproduced by Amy Wagers at Harvard a few years later,

Ovo je ponovno izvela Amy Wagers na Harvardu, par godina poslije

and others then showed that similar rejuvenating effects could be observed

te su i drugi pokazali slične učinke pomlađivanja

in the pancreas, the liver and the heart.

gušterače, jetre i srca.

But what I'm most excited about, and several other labs as well,

Ali ono što mene najviše uzbuđuje, još neke laboratorije također,

is that this may even apply to the brain.

je da se ovo može primijeniti čak i na mozak.

So, what we found is that an old mouse exposed to a young environment

Dakle, ono što smo otkrili je da stari miš izložen mladom okolišu,

in this model called parabiosis,

u ovom modelu zvanom parabioza,

shows a younger brain --

pokazuje mlađi mozak--

and a brain that functions better.

i mozak koji bolje funkcionira.

And I repeat:

I ponavljam:

an old mouse that gets young blood through shared circulation

stari miš koji dobiva mladu krv zajedničkom cirkulacijom

looks younger and functions younger in its brain.

izgleda mlađe i mozak mu funkcionira mlađe.

So when we get older --

Dok starimo--

we can look at different aspects of human cognition,

možemo gledati različite aspekte ljudske kognicije,

and you can see on this slide here,

i možete vidjeti na ovom slajdu,

we can look at reasoning, verbal ability and so forth.

možemo vidjeti razumijevanje, verbalne sposobnosti i tako dalje.

And up to around age 50 or 60, these functions are all intact,

I do negdje 50. ili 60.godine ove su funkcije netaknute

and as I look at the young audience here in the room, we're all still fine.

i dok gledam u mladu publiku u ovoj prostoriji, mi smo svi još uvijek u redu.

(Laughter)

(Smijeh)

But it's scary to see how all these curves go south.

Ali zastrašujuće je vidjeti kako sve te krivulje padaju.

And as we get older,

I kako starimo,

diseases such as Alzheimer's and others may develop.

bolesti poput Alzheimera i drugih se mogu razviti.

We know that with age, the connections between neurons --

Znamo da s godinama veze između neurona--

the way neurons talk to each other, the synapses -- they start to deteriorate;

način na koji neuroni komuniciraju, sinapse-- počinju propadati;

neurons die, the brain starts to shrink,

neuroni odumiru, mozak odumire,

and there's an increased susceptibility for these neurodegenerative diseases.

povećana je podložnost tim neurodegenerativnim bolestima.

One big problem we have -- to try to understand how this really works

Veliki problem koji imamo -- pokušati razumjeti kako to doista funkcionira

at a very molecular mechanistic level --

na molekularnoj, mehaničkoj razini --

is that we can't study the brains in detail, in living people.

je da ne možemo detaljno proučavati mozak u živučim ljudima.

We can do cognitive tests, we can do imaging --

Možemo vršiti kognitivne testove, možemo oslikavati mozak--

all kinds of sophisticated testing.

razna sofisticirana testiranja.

But we usually have to wait until the person dies

Ali obično moramo čekati da osoba umre

to get the brain and look at how it really changed through age or in a disease.

da dobijemo mozak i uvid u to kako se stvarno promijenio s godinama ili u bolesti.

This is what neuropathologists do, for example.

To rade neuropatolozi, na primjer.

So, how about we think of the brain as being part of the larger organism.

Kako bi bilo da zamislimo mozak kao dio većeg organizma.

Could we potentially understand more

Bismo li mogli razumjeti više

about what happens in the brain at the molecular level

o tome što se događa u mozgu na molekularnoj razini,

if we see the brain as part of the entire body?

kada bismo gledali mozak kao dio cijelog tijela?

So if the body ages or gets sick, does that affect the brain?

Dakle, ako tijelo stari ili se razboli, utječe li to na mozak?

And vice versa: as the brain gets older, does that influence the rest of the body?

I obrnuto: ako mozak stari, utječe li to na ostatak tijela?

And what connects all the different tissues in the body

A ono što povezuje sva različita tkiva u tijelu

is blood.

je krv.

Blood is the tissue that not only carries cells that transport oxygen, for example,

Krv je tkivo koje, ne samo da prenosi stanice koje nose kisik, na primjer,

the red blood cells,

crvene krvne stanice,

or fights infectious diseases,

ili koje se bore sa zaraznim bolestima,

but it also carries messenger molecules,

nego i prenosi glasničke molekule,

hormone-like factors that transport information

faktore slične hormonima koji prenose informacije

from one cell to another, from one tissue to another,

iz jedne stanice u drugu, iz jednog tkiva u drugo,

including the brain.

uključujući i mozak.

So if we look at how the blood changes in disease or age,

Dakle, ako pogledamo kako se krv mijenja u bolesti ili s godinama

can we learn something about the brain?

možemo li naučiti nešto o mozgu?

We know that as we get older, the blood changes as well,

Znamo da se, dok starimo,naša krv također mijenja,

so these hormone-like factors change as we get older.

tako da se ti faktori slični hormonima mijenjaju dok starimo.

And by and large, factors that we know are required

I većinom, faktori za koje znamo da su potrebni

for the development of tissues, for the maintenance of tissues --

za razvoj tkiva, za održavanje tkiva-

they start to decrease as we get older,

njihov broj se smanjuje kako starimo,

while factors involved in repair, in injury and in inflammation --

dok se broj faktora uključenih u popravke, kod ozljede ili upale--

they increase as we get older.

povećava kako starimo.

So there's this unbalance of good and bad factors, if you will.

Dakle, možemo reći da postoji neravnoteža tih dobrih i loših faktora.

And to illustrate what we can do potentially with that,

I da vam zornije prikažem što možda možemo napraviti s tim,

I want to talk you through an experiment that we did.

želim vas provesti kroz eksperiment koji smo proveli.

We had almost 300 blood samples from healthy human beings

Imali smo gotovo 300 uzoraka krvi iz zdravih ljudskih bića,

20 to 89 years of age,

između 20. i 89. godine,

and we measured over 100 of these communication factors,

i izmijerili smo preko 100 ovih komunikacijskih faktora,

these hormone-like proteins that transport information between tissues.

ovih proteina sličnih hormonima koji prenose informacije među tkivima.

And what we noticed first

I ono što smo prvo primijetili

is that between the youngest and the oldest group,

je da se između najmlađe i najstarije grupe

about half the factors changed significantly.

oko polovica faktora značajno promijenila.

So our body lives in a very different environment as we get older,

Dakle, naše tijelo živi u veoma drukčijem okolišu dok starimo,

when it comes to these factors.

kada uzmemo u obzir te faktore.

And using statistical or bioinformatics programs,

I koristeći statističke i bioinformatičke programe,

we could try to discover those factors that best predict age --

mogli smo pokušati otkriti te faktore koji nabolje predviđaju dob--

in a way, back-calculate the relative age of a person.

na neki način, unatrag zbrojimo relativnu dob osobe.

And the way this looks is shown in this graph.

I kako to izgleda prikazano je grafom.

So, on the one axis you see the actual age a person lived,

Dakle, na jednoj osi vidite stvarnu dob koju je odoba doživjela,

the chronological age.

kronološku dob.

So, how many years they lived.

Dakle, koliko su živjeli.

And then we take these top factors that I showed you,

I onda izdvojimo ove gornje faktore koje sam vam pokazao

and we calculate their relative age, their biological age.

i izračunamo relativnu dob, biološku dob.

And what you see is that there is a pretty good correlation,

I ono što zamjećujete je da postoji dosta dobra korelacija,

so we can pretty well predict the relative age of a person.

tako da možemo predvidjeti relativnu dob osobe.

But what's really exciting are the outliers,

Ali ono što je doista uzbudljivo su, iznimke,

as they so often are in life.

kao što su često i u životu.

You can see here, the person I highlighted with the green dot

Ovdje možete vidjeti, osoba koju sam naglasio zelenom točkom,

is about 70 years of age

ima oko 70 godina,

but seems to have a biological age, if what we're doing here is really true,

ali izgleda da joj je biološka dob, ako je ono što činimo stvarno istinito,

of only about 45.

samo 45 godina.

So is this a person that actually looks much younger than their age?

Je li ovo osoba koja zapravo izgleda puno mlađe od svojih godina?

But more importantly: Is this a person who is maybe at a reduced risk

Ali još važnije: hoće li ova osoba, koja možda ima smanjen rizik

to develop an age-related disease and will have a long life --

razvitka bolesti vezane uz starenje i proživjeti dug život-

will live to 100 or more?

živjeti 100 ili više godina?

On the other hand, the person here, highlighted with the red dot,

S druge strane, ova osoba, naglašena crvenom točkom,

is not even 40, but has a biological age of 65.

nema ni 40 godina, ali biološka dob joj je 65.

Is this a person at an increased risk of developing an age-related disease?

Je li ovo osoba povećanog rizika za razvoj bolesti vezane uz starenje?

So in our lab, we're trying to understand these factors better,

U našem laboratoriju pokušavamo bolje razumjeti ove faktore,

and many other groups are trying to understand,

i mnoge druge grupe pokušavaju razumjeti,

what are the true aging factors,

koji su stvarni faktori starenja

and can we learn something about them to possibly predict age-related diseases?

i možemo li nešto naučiti o njima da bismo predvidjeli bolesti starenja?

So what I've shown you so far is simply correlational, right?

Ono što sam vam do sada pokazao je jednostavno u korelaciji, je li tako?

You can just say, "Well, these factors change with age,"

Možete reći: "Pa, ovi se faktori mijenjaju s godinama",

but you don't really know if they do something about aging.

ali ne znate zapravo imaju li veze sa starenjem.

So what I'm going to show you now is very remarkable

Ono što ču vam sada pokazati je izvanredno

and it suggests that these factors can actually modulate the age of a tissue.

i predlaže da ovi faktori zapravo mogu modulirati starost tkiva.

And that's where we come back to this model called parabiosis.

I tada se vraćamo ovom modelu zvanom parabioza.

So, parabiosis is done in mice

Dakle, parabioza se vrši na miševima,

by surgically connecting the two mice together,

tako da dva miša kirurški povežu

and that leads then to a shared blood system,

i to dovodi do dijeljenja krvnog sustava,

where we can now ask, "How does the old brain get influenced

sad se možemo pitati: " Kako mlada krv utječe na

by exposure to the young blood?"

stari mozak koji joj je izložen?"

And for this purpose, we use young mice

Za ovaj pokus koristimo mlade miševe,

that are an equivalency of 20-year-old people,

koji se jednaki 20-godišnjim ljudima,

and old mice that are roughly 65 years old in human years.

i stare koji imaju otprilike 65 ljudskih godina.

What we found is quite remarkable.

Ono što smo otkrili je prilično fascinatno.

We find there are more neural stem cells that make new neurons

Otkrili smo da ima više živčanih matičnih stanica koje proizvode nove neurone

in these old brains.

u tim starim mozgovima.

There's an increased activity of the synapses,

Povećana je aktivnost sinapsi,

the connections between neurons.

mjesta vezanja između sva neurona.

There are more genes expressed that are known to be involved

Više je izraženih gena za koje se zna da sudjeluju

in the formation of new memories.

u stvaranju novog pamćenja.

And there's less of this bad inflammation.

I ima manje upala.

But we observed that there are no cells entering the brains of these animals.

Ali uočili smo da nema stanica koje ulaze u mozak tih životinja.

So when we connect them,

Dakle, kada ih povežemo

there are actually no cells going into the old brain, in this model.

zapravo nema stanica koje ulaze u stari mozak, u ovom modelu.

Instead, we've reasoned, then, that it must be the soluble factors,

Umjesto toga, zaključili smo da to moraju biti topljivi faktori,

so we could collect simply the soluble fraction of blood which is called plasma,

tako da jednostavno možemo prikupiti topljivi dio krvi zvan plazma

and inject either young plasma or old plasma into these mice,

i ubrizgati, ili mladu plazmu, ili statu plazmu u te miševe

and we could reproduce these rejuvenating effects,

i mogli bismo proizvesti te pomlađujuće učinke,

but what we could also do now

ali ono što također možemo napraviti

is we could do memory tests with mice.

je testiranje pamćenja miševa.

As mice get older, like us humans, they have memory problems.

Dok miševi stare, kao mi ljudi, imaju probleme s pamćenjem.

It's just harder to detect them,

Samo ih je teže pronaći,

but I'll show you in a minute how we do that.

ali za minutu ću vam pokazati kako.

But we wanted to take this one step further,

Ali htjeli smo ovo odnijeti korak dalje,

one step closer to potentially being relevant to humans.

korak bliže mogućem značaju za ljude.

What I'm showing you now are unpublished studies,

Ono što vam sada pokazujem su neobjavljene studije,

where we used human plasma, young human plasma,

u kojima smo koristili ljudsku plazmu, mladu ljudsku plazmu,

and as a control, saline,

i kao kontrolu, slanu otopinu,

and injected it into old mice,

ubrizgali smo ju u stare miševe

and asked, can we again rejuvenate these old mice?

i pitali, možemo li opet pomladiti te stare miševe?

Can we make them smarter?

Možemo li ih opametiti?

And to do this, we used a test. It's called a Barnes maze.

I da bismo to napravili, koristili smo test. Zove se Barnesov labirint.

This is a big table that has lots of holes in it,

Ovo je veliki stol koji na sebi ima mnogo rupa

and there are guide marks around it,

i oko njih su kazala,

and there's a bright light, as on this stage here.

svijetli jako svijetlo, kao ovdje na pozornici.

The mice hate this and they try to escape,

Miševi mrze to i pokušavaju pobjeći

and find the single hole that you see pointed at with an arrow,

i pronađu jednu jedinu rupu na koju pokazuje strelica,

where a tube is mounted underneath

ispod koje je cijev

where they can escape and feel comfortable in a dark hole.

kroz koju mogu pobijeći i osjećati se ugodno u crnoj rupi.

So we teach them, over several days,

Mi ih učimo, nekoliko dana,

to find this space on these cues in the space,

da pronađu taj prostor na ovim preprekama u prostoru,

and you can compare this for humans,

a to možete usporediti s ljudima

to finding your car in a parking lot after a busy day of shopping.

kada traže svoj automobil na parkiralištu nakon napornog dana kupovine.

(Laughter)

(Smijeh)

Many of us have probably had some problems with that.

Mnogi od nas su vjerojatno imali problema s tim.

So, let's look at an old mouse here.

Hajmo pogledati ovog starog miša.

This is an old mouse that has memory problems,

Ovo je stari miš koji ima problema s pamćenjem,

as you'll notice in a moment.

primijetit ćete to za trenutak.

It just looks into every hole, but it didn't form this spacial map

Gleda u svaku rupu, ali nije stvorio prostornu kartu

that would remind it where it was in the previous trial or the last day.

gdje je bila prošloga pokušaja ili dana.

In stark contrast, this mouse here is a sibling of the same age,

U snažnom kontrastu, ovaj je miš jednako star brat,

but it was treated with young human plasma for three weeks,

ali bio je tretiran mladom ljudskom plazmom tri tjedna,

with small injections every three days.

malom injekcijom svaka tri dana.

And as you noticed, it almost looks around, "Where am I?" --

Odmah primjećujete, gotovo gleda uokolo, "Gdje sam?"--

and then walks straight to that hole and escapes.

i onda dohoda ravno do te rupe i pobjegne.

So, it could remember where that hole was.

Dakle, sjetio se gdje je bila rupa.

So by all means, this old mouse seems to be rejuvenated --

Dakle, ovaj se miš je prema svim pokazateljima čini pomlađen--

it functions more like a younger mouse.

funkcionira više kao mladi miš.

And it also suggests that there is something

I to predlaže da također postoji nešto,

not only in young mouse plasma, but in young human plasma

ne samo u plazmi mladog miša, nego i u plazmi mladog čovjeka,

that has the capacity to help this old brain.

što ima kapacitet pomoći ovom starom mozgu.

So to summarize,

Dakle, da sažmem,

we find the old mouse, and its brain in particular, are malleable.

smatramo da je stari miš, i pogotovo njegov mozak, u mogućnosti promjene.

They're not set in stone; we can actually change them.

Nisu zabetonirani; možemo ih mijenjati.

It can be rejuvenated.

Može se pomladiti.

Young blood factors can reverse aging,

Faktori mlade krvi mogu preokrenuti proces tarenja

and what I didn't show you --

i ono što vam nisam pokazao--

in this model, the young mouse actually suffers from exposure to the old.

u ovom modelu, mladi miš zapravo pati od izlaganja starom.

So there are old-blood factors that can accelerate aging.

Dakle, postoji faktori stare krvi koji mogu ubrzati starenje.

And most importantly, humans may have similar factors,

I najvažnije, ljudi možda imaju slične faktore,

because we can take young human blood and have a similar effect.

jer možemo uzeti mladu ljudsku krv i postići sličan učinal.

Old human blood, I didn't show you, does not have this effect;

Stara ljudska krv, nisam vam pokazao, nema taj učinak;

it does not make the mice younger.

ne pomlađuje miševe.

So, is this magic transferable to humans?

Dakle, je li ta magija primijenjiva na ljudima?

We're running a small clinical study at Stanford,

Provodimo malu kliničku studiju na Stanfordu,

where we treat Alzheimer's patients with mild disease

u kojoj tretiramo ljude oboljele od Alzheimera blagog oblika

with a pint of plasma from young volunteers, 20-year-olds,

s malo plazme mladih volontera, 20-godišnjaka,

and do this once a week for four weeks,

činimo to jednom tjedno četiri tjedna

and then we look at their brains with imaging.

i zatim pogledamo njihove mozgove oslikavanjem.

We test them cognitively,

Kognitivno ih testiramo

and we ask their caregivers for daily activities of living.

i pitamo njihove njegovatelje za dnevne životne aktivnosti.

What we hope is that there are some signs of improvement

Ono čemu se nadamo su neki znakovi poboljšanja

from this treatment.

od tog tretmana.

And if that's the case, that could give us hope

I ako se to dogodi, to bi nam moglo dat nadu

that what I showed you works in mice

da ono što sam vam pokazao da funkcionira na miševima,

might also work in humans.

možda također funkcionira na ljudima.

Now, I don't think we will live forever.

Ne mislim da ćemo živjeti vječno.

But maybe we discovered

Ali možda smo otkrili

that the Fountain of Youth is actually within us,

da je Fontana mladosti zapravo u nama

and it has just dried out.

i da je upravo presušila.

And if we can turn it back on a little bit,

I ako ju opet možemo malo uključiti,

maybe we can find the factors that are mediating these effects,

možda možemo naći faktore koji sudjeluju u tim učincima,

we can produce these factors synthetically

možemo sintetički proizvesti te faktore

and we can treat diseases of aging, such as Alzheimer's disease

i možemo tretirati bolesti vezane uz starenje, poput Alzheimera

or other dementias.

ili drugih demencija.

Thank you very much.

Puno vam hvala.

(Applause)

(Pljesak)