18 minutes is an absolutely brutal time limit, so I'm going to dive straight in, right at the point where I get this thing to work. Here we go. I'm going to talk about five different things. I'm going to talk about why defeating aging is desirable. I'm going to talk about why we have to get our shit together, and actually talk about this a bit more than we do. I'm going to talk about feasibility as well, of course. I'm going to talk about why we are so fatalistic about doing anything about aging. And then I'm going spend perhaps the second half of the talk talking about, you know, how we might actually be able to prove that fatalism is wrong, namely, by actually doing something about it.
18 minuta eshte nje kohe plotesisht e pamjaftueshme keshtu qe do te jem i drejt per drejt si funksionon kjo gje. Une do te flas per 5 gjera te ndryshme Une do te flas perse te mposhtesh plakjen eshte e deshirueshme. Une do te flas perse duhet te jemi te organizuar, dhe ne fakt do te flas rreth kesaj me shume. Une do te flas per realizushmerine, natyrisht. Une do te flas perse jemi pesimist rreth gjithckaje qe ka te bej me plakjen. dhe ndoshta pastaj pjesen e dyte te fjalimit do ta shpenzoj se si mund ta vertetojm se pesimismi eshte gabim, duke bere dicka rreth saj.
I'm going to do that in two steps. The first one I'm going to talk about is how to get from a relatively modest amount of life extension -- which I'm going to define as 30 years, applied to people who are already in middle-age when you start -- to a point which can genuinely be called defeating aging. Namely, essentially an elimination of the relationship between how old you are and how likely you are to die in the next year -- or indeed, to get sick in the first place. And of course, the last thing I'm going to talk about is how to reach that intermediate step, that point of maybe 30 years life extension.
Une do ta bej kete ne dy hapa. Gjeja e pare per te cilen do flas eshte si mund te arrijm te zgjasim jetes me modesti te cilen do ta percaktoja 30 vjec, te cilet jane ne moshe te mesme kur arrin nje pike ku i dorezoheni plakjes. Esencialisht nje eleminim i lidhjes midis sa vjec je, dhe sa eshte mundesi te vdesesh vitin tjeter ose te semuresh. Dhe natyrisht, gjeja e fundit per te cilen do te flas eshte se si mund te arrijm fazen e ndermjetme. pika ku te rrisim kohezgjatjen me 30 vjet.
So I'm going to start with why we should. Now, I want to ask a question. Hands up: anyone in the audience who is in favor of malaria? That was easy. OK. OK. Hands up: anyone in the audience who's not sure whether malaria is a good thing or a bad thing? OK. So we all think malaria is a bad thing. That's very good news, because I thought that was what the answer would be. Now the thing is, I would like to put it to you that the main reason why we think that malaria is a bad thing is because of a characteristic of malaria that it shares with aging. And here is that characteristic. The only real difference is that aging kills considerably more people than malaria does.
Atehere, do te filloj me pyetjen perse duhet. Tani dua te bej nje pyetje. Ngrini duart; te gjithe ata qe jane pro malarias? Kjo ishte e thjesht. OK. OK. Ngini duarte, ata ne audience te cilet nuk jane te sigurt nese malaria eshte dicka e mire apo e keqe? OK. Keshtu qe te gjithe mendojm se malaria eshte dicka e keqe. Ky eshte lajm i mire, pasi kjo eshte pergjigja qe kisha menduar. Gjeja qe une dua qe ju te kuptoni eshte se arsye kryesore perse ne mendojm se malaria eshte gje e keqe eshte per shkak te karakteristikes qe malaria ka me plakjen. Dhe ja ku eshte kjo karakteristike. Diferenca e vetme eshte se plakja vret konsiderueshem me shum njerez se malaria.
Now, I like in an audience, in Britain especially, to talk about the comparison with foxhunting, which is something that was banned after a long struggle, by the government not very many months ago. I mean, I know I'm with a sympathetic audience here, but, as we know, a lot of people are not entirely persuaded by this logic. And this is actually a rather good comparison, it seems to me. You know, a lot of people said, "Well, you know, city boys have no business telling us rural types what to do with our time. It's a traditional part of the way of life, and we should be allowed to carry on doing it. It's ecologically sound; it stops the population explosion of foxes." But ultimately, the government prevailed in the end, because the majority of the British public, and certainly the majority of members of Parliament, came to the conclusion that it was really something that should not be tolerated in a civilized society.
Tani, dua qe ne audience, sidomos ne Britani, te krahasojm gjahun e dhelprave, e cila eshte dicka qe u ndalua pas shum veshtiresive, nga qeveria jo shume muaj me pare. E di se kam nje audience dashamirese ketu, por, sic e dime, shume njerez nuk jam shume te bindur nga kjo logjike. Dhe faktikisht kjo eshte nje krahasim shum i mire, sipas meje. E dini se shum njerez thane, "Ata te qytetit nuk kane pune te na tregojn ne fshatareve se cfare te bejm me kohen tone. Eshte zakon dhe pjese e jetes tone, dhe ne duhet te jemi te lire te vazhdojm ta bejm kete. Ekologjikisht nenkupton se ndalon nje shperthim te popullates se dhelprave." Por, perfundimisht qeveria mbizoteroi ne fund, sepse shumica e publikut Britanik, dhe sidomos shumica e antareve te perlamentit, arriten ne perfundimin se ishte vertet dicka qe nuk hej toleruar ne nje shoqeri te civilizuar.
And I think that human aging shares all of these characteristics in spades. What part of this do people not understand? It's not just about life, of course -- (Laughter) -- it's about healthy life, you know -- getting frail and miserable and dependent is no fun, whether or not dying may be fun. So really, this is how I would like to describe it. It's a global trance. These are the sorts of unbelievable excuses that people give for aging. And, I mean, OK, I'm not actually saying that these excuses are completely valueless. There are some good points to be made here, things that we ought to be thinking about, forward planning so that nothing goes too -- well, so that we minimize the turbulence when we actually figure out how to fix aging.
Une mendoj se plakja e njerezimit ndan te gjitha keto karakteristika me shpate. Cilen pjese nuk kuptojne njerezit? Singurisht nuk ka te bej vec me jeten (buzeqeshje) ka te bej me jeten e shendetshme te jesh i brisht, i mjere, dhe i varur nuk eshte qejf, as vdekja nuk eshte qejf. At'here, keshtu kam qejf ta pershkruaj. Eshte nje ekstaze globale. Keto jane burimet e justifikimeve te papranueshme. qe njerezit thone rreth plakjes. Ok, nuk eshte se dua te them qe keto justifikime jane komplete te pa vlera. Ka disa pika te rendesishme qe duhet kushtuar vemendje. Gjera te cilat duhet ti mendojm per planet e ardhshme ne menyre qe gjerat mos te shkojne shume mire, qe te minimizojm turbulencat kur ta gjejme sesi mund ta rregullojme plakjen.
But these are completely crazy, when you actually remember your sense of proportion. You know, these are arguments; these are things that would be legitimate to be concerned about. But the question is, are they so dangerous -- these risks of doing something about aging -- that they outweigh the downside of doing the opposite, namely, leaving aging as it is? Are these so bad that they outweigh condemning 100,000 people a day to an unnecessarily early death? You know, if you haven't got an argument that's that strong, then just don't waste my time, is what I say. (Laughter)
Por keto jane cmendurira, kur faktikisht kujtojm sensin e proporcionit. Keto jane argumente, gjera te cilat do te ishte legjitime qe te shqetesoheshim. Por pyetja eshte, a jane keto kaq te rrezikshme keto rreziqe per te bere dicka rreth plakjes te cilat peshojn me shume sesa duhet te kunderten, duke e lene plakjen te afrohet? a jane keto aq te keqija sa qe denojn 100,000 njerez ne dite me nje vdekje te parakohshme e te panevojshme. Nese nuk ke ndonje argument aq te fort, atehere mos ma harxho kohen kot, kete kam per te thene. (buzeqeshje)
Now, there is one argument that some people do think really is that strong, and here it is. People worry about overpopulation; they say, "Well, if we fix aging, no one's going to die to speak of, or at least the death toll is going to be much lower, only from crossing St. Giles carelessly. And therefore, we're not going to be able to have many kids, and kids are really important to most people." And that's true. And you know, a lot of people try to fudge this question, and give answers like this. I don't agree with those answers. I think they basically don't work. I think it's true, that we will face a dilemma in this respect. We will have to decide whether to have a low birth rate, or a high death rate. A high death rate will, of course, arise from simply rejecting these therapies, in favor of carrying on having a lot of kids.
Tani, eshte nje argument qe disa njerez vertete mendojn se eshte shum i fort, ia ku eshte. Njerezit shqetesohen per mbipopullimin; thone ata, "Epo mire, nese e ndreqim plakjen, asnje nuk do vdes per te folur, ose te pakten taksa e vdekjes do jet shum me e ulet, vetem duke kaluar St. Giles pa kujdes. Prandaj, ne nuk do te jemi ne gjendje te lindim shume femije, dhe femijet jane shum te rendesishem per shum njerez." Kjo eshte e vertete. Dhe e dini ca, shume njerez mundohen ta evitojn kete pyetje, and pergjigjen keshtu. Une nuk jam dakort me keto pergjigje. Une ne parim mendoj se nuk funksionojne. Une mendoj se eshte e verete, do te perballemi me nje dileme. Do na duhet te vendosim nese duhet te kemi nje shkalle te lindjes te ulet, ose shkalle te lart te vdekjes. Nje shkalle e lart e vdekjes, sigurisht, vjen thjesht nga kundershtimi i ketyre terapive, ne favor te te pasurit shume femije.
And, I say that that's fine -- the future of humanity is entitled to make that choice. What's not fine is for us to make that choice on behalf of the future. If we vacillate, hesitate, and do not actually develop these therapies, then we are condemning a whole cohort of people -- who would have been young enough and healthy enough to benefit from those therapies, but will not be, because we haven't developed them as quickly as we could -- we'll be denying those people an indefinite life span, and I consider that that is immoral. That's my answer to the overpopulation question.
Dhe une them se kjo eshte ne rregull, e ardhmja e njerezimit ka te drejt te vendos keshtu. Ajo cka nuk eshte e drejt eshte qe ne te bejme kete zgjedhje ne emer te te ardhmes. nese, ne luhatemi, hezitojm, dhe aktualisht nuk i zhvillojme keto terapi, athere ne po denojm nje numer te madh njerezish, te cilet do te ishin te rinj mjaftueshem dhe te shendetshem mjaftueshem qe te perfitonin nga keto terapi, por nuk do te ndodhe, sepse ne nuk i kemi zhvilluar aq shpejt sa mundeshim-- do t'i mohojm ketyre njerezve nje jetegjatesi te pacaktuar, dhe une e konsideroj kete imporale. Kjo eshte pergjigja ime rreth pyetjes se mbipopullimit.
Right. So the next thing is, now why should we get a little bit more active on this? And the fundamental answer is that the pro-aging trance is not as dumb as it looks. It's actually a sensible way of coping with the inevitability of aging. Aging is ghastly, but it's inevitable, so, you know, we've got to find some way to put it out of our minds, and it's rational to do anything that we might want to do, to do that. Like, for example, making up these ridiculous reasons why aging is actually a good thing after all. But of course, that only works when we have both of these components. And as soon as the inevitability bit becomes a little bit unclear -- and we might be in range of doing something about aging -- this becomes part of the problem. This pro-aging trance is what stops us from agitating about these things. And that's why we have to really talk about this a lot -- evangelize, I will go so far as to say, quite a lot -- in order to get people's attention, and make people realize that they are in a trance in this regard. So that's all I'm going to say about that.
Athere pika tjeter eshte, tani, perse duhet te jemi pak me teper active per kete? dhe pergjigja themelore eshte se, pro plakja ekstaze nuk eshte aq budallallik sa duket. Perballimi i plakjes eshte nje ceshtje e ndjeshme. Plakja eshte e ngadalte, por e pashmangshme, duhet te gjejm nje menyre qe ta heqim nga mendjet tona, dhe eshte e arsyeshme qe te bejm gjithcka qe mundemi per ta bere kete gje. Si per shembull te shpikim keto justifikime qesharake perse plakja eshte nje gje e mire ne fund te fundit. Por sigurisht, kjo do te funksiononte vetem nese do t'i kishim te dy keta perberes. Dhe ne momentin kur paevitueshmeria behet e paqart athere ne do te jemi ne gamen e te berit dicka rreth plakjes kjo behet pjese e problemit. Ky trance pro- plakjes eshte ajo cka na ndalon ne te agjitohemi rreth ketyre gjerave. Dhe prandaj ne duhet te flasim shum rreth kesaj-- evangelize, une do te vazhdoj deri aty, sa te kem then mjaftueshem-- ne menyre qe te terheq vemendjen e njerezve dhe ti beje njerezit te kuptojne qe jane ne nje trance rreth kesaj ceshtje. Pra, kjo eshte cka une dua te them rreth kesaj ceshtje.
I'm now going to talk about feasibility. And the fundamental reason, I think, why we feel that aging is inevitable is summed up in a definition of aging that I'm giving here. A very simple definition. Aging is a side effect of being alive in the first place, which is to say, metabolism. This is not a completely tautological statement; it's a reasonable statement. Aging is basically a process that happens to inanimate objects like cars, and it also happens to us, despite the fact that we have a lot of clever self-repair mechanisms, because those self-repair mechanisms are not perfect.
Une tani do te flas per realizueshmerine. Dhe arsyen themelore, mendoj une, perse ne ndihemi se plakja eshte e pashmangshme eshte e pjese e perkufizimit te plakjes qe une kam ketu. Nje perkufizim shume i thjesht. Plakja eshte pasoje e te qenit te gjalle, si pershembull, metabolizmi. Kjo nuk eshte nje deklarate e vertete; eshte nje dekrata e arsyeshme. Plakja eshte nje proces qe ndodh tek objektet e pajete, si makinat, dhe gjithashtu ndodh tek ne, pavarsisht nga fakti se ne kemi shum mekanizma te zgjuar vete-riparimi, per shkak se keto mekanizma vete-riparimi nuk jane perfekte.
So basically, metabolism, which is defined as basically everything that keeps us alive from one day to the next, has side effects. Those side effects accumulate and eventually cause pathology. That's a fine definition. So we can put it this way: we can say that, you know, we have this chain of events. And there are really two games in town, according to most people, with regard to postponing aging. They're what I'm calling here the "gerontology approach" and the "geriatrics approach." The geriatrician will intervene late in the day, when pathology is becoming evident, and the geriatrician will try and hold back the sands of time, and stop the accumulation of side effects from causing the pathology quite so soon. Of course, it's a very short-term-ist strategy; it's a losing battle, because the things that are causing the pathology are becoming more abundant as time goes on.
Ne parim, metabolizmi, i ciki perkufizohet se eshte gjithcka qe na mban gjall cdo dite, ka pasoja anesore. Keto arsye anesore akumulohen dhe shkaktojn patologji. Ky eshte perkufizim perfekt. Mund te shprehemi ne kete menyre: mund te themi, se ne e kemi kete zinxhir eventesh. Dhe jane dy gjera qe ndodhin, simas shumices se njerezve, persa i perket shtyrjes se plakjes. Keto jane ato cka une do ti quaja trajtimi gjerondologjik dhe trajtimi geriatrik. Gjerondologjia do te perfshihet me vone, kur patologjia te jete e dukshme, dhe geriatriku do te mundohet te ndaloje kohen, dhe te ndaloje akumulimin e pasojave anesore qe te shkaktojne nje patologji kaq heret. Sigurisht, eshte nje strategji kohe shkurter, eshte nje beteje e humbur, sepse gjerat qe shkaktojn patologjine jane duke u shumuar me kalimin e kohes.
The gerontology approach looks much more promising on the surface, because, you know, prevention is better than cure. But unfortunately the thing is that we don't understand metabolism very well. In fact, we have a pitifully poor understanding of how organisms work -- even cells we're not really too good on yet. We've discovered things like, for example, RNA interference only a few years ago, and this is a really fundamental component of how cells work. Basically, gerontology is a fine approach in the end, but it is not an approach whose time has come when we're talking about intervention. So then, what do we do about that? I mean, that's a fine logic, that sounds pretty convincing, pretty ironclad, doesn't it?
Trajtimi gjerondologjik duket me permtimprues ne pamje te pare, sepse parandalimi eshte me mire se kurimi. Por fatkeqesisht puna eshte se ne nuk e kuptojm shume mire metabolizmin. Ne fakt, ne jemi per te ardhur keq persa i perket menyres se si funksionon organizmi-- edhe rreth qelizave nuk dime shume. Kemi zbuluar gjera, si per shembull, ARN-ja vetem disa vite me pare, dhe kjo eshte dicka themelore sesi qelizat funksionojne. Ne parim, gjerondologjia eshte nje trajtim i mire, por nuk eshte nje trajtim per kohen qe ka ardhur, kur ne po flisnim per nje nderhyrje. At'here, cfare do te bejme rreth kesaj? Dua te them qe kjo eshte llogjike, tingullon teper bindese, apo jo?
But it isn't. Before I tell you why it isn't, I'm going to go a little bit into what I'm calling step two. Just suppose, as I said, that we do acquire -- let's say we do it today for the sake of argument -- the ability to confer 30 extra years of healthy life on people who are already in middle age, let's say 55. I'm going to call that "robust human rejuvenation." OK. What would that actually mean for how long people of various ages today -- or equivalently, of various ages at the time that these therapies arrive -- would actually live? In order to answer that question -- you might think it's simple, but it's not simple. We can't just say, "Well, if they're young enough to benefit from these therapies, then they'll live 30 years longer." That's the wrong answer. And the reason it's the wrong answer is because of progress.
Por nuk eshte. Perpara se t'ju them perse nuk eshte, do te flas pak per ate cka une quaj faza e dyte. Supozo, sic thashe, se ne fitojm-- le te themi se do ta bejm sot per hir te diskutimit -- aftesine per te akorduar 30 vjet extra ne nje jete te shendetshme tek njerezit qe jane ne moshen mesatare, le te themi 55 vjec. Do ta quaj kete nje perteritje te fuqishme te njeriut. OK. Cfare kjo do te nenkuptoj ne te vertete se sa gjate njerez te moshave te ndryshme sot -- ose, mosha te ndryshme kur koha e terapive te vije -- do te jetonin? Ne menyre qe ti pergjigjemi kesaj pyetje -- do te mendoje se eshte e thjesht, por nuk eshte aq e thjesht. Nuk mund te themi thjesht, "Nese je i ri mjaftueshem per te perfituar nga keto terapi, do te mund te jetoni 30 vjet me shume." Kjo eshte pergjigja e gabuar. Dhe arsyeja perse eshte e gabuar eshte per shkak te progresit.
There are two sorts of technological progress really, for this purpose. There are fundamental, major breakthroughs, and there are incremental refinements of those breakthroughs. Now, they differ a great deal in terms of the predictability of time frames. Fundamental breakthroughs: very hard to predict how long it's going to take to make a fundamental breakthrough. It was a very long time ago that we decided that flying would be fun, and it took us until 1903 to actually work out how to do it. But after that, things were pretty steady and pretty uniform. I think this is a reasonable sequence of events that happened in the progression of the technology of powered flight. We can think, really, that each one is sort of beyond the imagination of the inventor of the previous one, if you like. The incremental advances have added up to something which is not incremental anymore.
Jane dy lloje progresi teknologjik, per kete qellim. Ato jane themelore, parime te medha, dhe jane zhvillim i perpunimeve te ketyre parimeve. Tani, keto kane nje ndryshim te madh, persa i perket parashikimit kohore. Parime themelore: shume e veshtire te parashikohen se sa kohe do te duhet te krijosh nje zbulim te madh themelore. Ka kaluar shume kohe qekur medonim se te flitironim do ishte qejf, dhe na u desh te prisnim deri ne 1903 qe ta benim kete. Por mbas kesaj, gjerat ishin shume te qendrueshme dhe uniforme. Mendoj se kjo eshte nje sekuence e arsyeshme e eventeve qe ndodhen ne zhvillimin e teknologjise se flytyrimit. Mund te mendojne, se gjithkush ishte pertej inmagjinates se shpikesit te meparshem, nese ju pelqen. Zhvillimi i avancimeve kishte shtuar dicka e cila nuk ishte me zhvillim.
This is the sort of thing you see after a fundamental breakthrough. And you see it in all sorts of technologies. Computers: you can look at a more or less parallel time line, happening of course a bit later. You can look at medical care. I mean, hygiene, vaccines, antibiotics -- you know, the same sort of time frame. So I think that actually step two, that I called a step a moment ago, isn't a step at all. That in fact, the people who are young enough to benefit from these first therapies that give this moderate amount of life extension, even though those people are already middle-aged when the therapies arrive, will be at some sort of cusp. They will mostly survive long enough to receive improved treatments that will give them a further 30 or maybe 50 years. In other words, they will be staying ahead of the game. The therapies will be improving faster than the remaining imperfections in the therapies are catching up with us.
Kjo eshte ajo cka shihet pas nje zbulimi te madh themelor. Dhe kjo vihet re ne lloje te ndryshme teknologjike. Kompjuterat, mund te shohesh nje ose me pak afat kohor, qe ndodhin sigurisht pak me vone. Shikoni kujdesin shendetsor. Dua te them, higjenen, vaksinat, antibiotiket -- te njejtat afate kohore. Pra une mendoj se ne fakt faza e dyte, qe une e quajta pak me pare, nuk eshte fare nje hap. Ku ne fakt, njerezit te cilet jane mjaftueshem te rinj te perfitojn prej ketyre terapive qe mundesojn kete shtese ne jetegjatesi, edhe pse keta njerez do jene ne moshen mesatare kur kjo teknologji te vije, do te jete ne kulmin e saj. Ata do te mbijetojn mjaftueshem per te marr trajtime te permiresuara qe do ti japi 30 ose ndoshta 50 vjet. Me fjale te tjera, ata do te ecin me kohen. Terapite do te permiresohen me shpejt sesa terapite e joperfekte te koheve te sotme.
This is a very important point for me to get across. Because, you know, most people, when they hear that I predict that a lot of people alive today are going to live to 1,000 or more, they think that I'm saying that we're going to invent therapies in the next few decades that are so thoroughly eliminating aging that those therapies will let us live to 1,000 or more. I'm not saying that at all. I'm saying that the rate of improvement of those therapies will be enough. They'll never be perfect, but we'll be able to fix the things that 200-year-olds die of, before we have any 200-year-olds. And the same for 300 and 400 and so on. I decided to give this a little name, which is "longevity escape velocity." (Laughter) Well, it seems to get the point across.
Kjo eshte nje pike shume e rendesishme per t'u prekur. Sepse, shum njerez, kur degjojne se une parashikoj se shum njerez qe jan gjalle sot do te jetojn 1,000 apo me shume, ata mendojne se une po them se ne do te shpikim terapi ne dekadad e ardhshme qe do te eleminojn plakjen teresisht dhe se keto terapi do te na lejojn te jetojm 1,000 apo me shume. Une nuk po them fare kete. Une po them se ritmi i zhvillimit te ketyre terapive do jete e mjaftueshme. Ato nuk do jen kurre perfekt, por do te jemi ne gjendje te ndreqim gjerat qe 200- vjecaret do te vdesin, perpara se te kemi ndonje 200- vjecare. E njejta gje per 300, 400, e keshtu me rradhe. Kam vendosur ti jap nje emer kesaj, qe eshte "logevity escape velocity." (Buzeqeshje) Mesa duket e transmetova kuptimin.
So, these trajectories here are basically how we would expect people to live, in terms of remaining life expectancy, as measured by their health, for given ages that they were at the time that these therapies arrive. If you're already 100, or even if you're 80 -- and an average 80-year-old, we probably can't do a lot for you with these therapies, because you're too close to death's door for the really initial, experimental therapies to be good enough for you. You won't be able to withstand them. But if you're only 50, then there's a chance that you might be able to pull out of the dive and, you know -- (Laughter) -- eventually get through this and start becoming biologically younger in a meaningful sense, in terms of your youthfulness, both physical and mental, and in terms of your risk of death from age-related causes. And of course, if you're a bit younger than that, then you're never really even going to get near to being fragile enough to die of age-related causes.
At'here, keto trajektore ketu tregojne sesi ne presim qe njerezit te jetojne, persa i perket pritshmerise se jetegjatesise, duke matur shendetin e tyre, per moshat qe ata kishin kur keto terapi erdhen. Nese ti je 100, ose nese ti je 80 -- dhe mesatarisht 80-vjecar, ne nuk do mund te bejme shume per ju me keto terapi, sepse jeni shume afer vdekjes ne menyre qe terapia eksperimentale, fillestare te jete mjaftueshem e mire per ty. Ju nuk do ishit ne gjendje ti perballonit ato. Por nese je vetem 50, at'here do te kishit nje shanse dhe mund t'ia dalesh mbane. (Buzeqeshje) dhe perfundimisht t'ia hedhesh kesaj dhe te fillosh te behesh biologjikisht i ri ne nje sense kuptimplot, persa i perket rinise suaj, fiziksht dhe psikologjikisht, dhe persa i perket rrezikut te vdekjes nga shkaqe te lidhura me moshen. Dhe sigurisht, nese je pak me i ri se kaq, at'here ju as nuk do te shkoni afer te qenit aq i brisht sa te vdisni nga shkaqe lidhur me moshen.
So this is a genuine conclusion that I come to, that the first 150-year-old -- we don't know how old that person is today, because we don't know how long it's going to take to get these first-generation therapies. But irrespective of that age, I'm claiming that the first person to live to 1,000 -- subject of course, to, you know, global catastrophes -- is actually, probably, only about 10 years younger than the first 150-year-old. And that's quite a thought.
Keshtu qe ky eshte nje perfundim i cilter, qe 150 vjecari i pare -- nuk e dime sesa vjec eshte ai person sot, sepse nuk e dime sesa kohe do duhet perpara se te hyjn gjenerata e pare e ketyre terapive. Por pavarsisht nga mosha, Une pretendoj qe personi i pare qe do jetoje 1,000 -- subjektive sigurisht, ndaj katastrofave globale -- eshte ne te vertet, vetem rreth 10 vjet me te rinj sesa 150 vjecari i pare. Dhe kjo eshte nje goxha mendim.
Alright, so finally I'm going to spend the rest of the talk, my last seven-and-a-half minutes, on step one; namely, how do we actually get to this moderate amount of life extension that will allow us to get to escape velocity? And in order to do that, I need to talk about mice a little bit. I have a corresponding milestone to robust human rejuvenation. I'm calling it "robust mouse rejuvenation," not very imaginatively. And this is what it is. I say we're going to take a long-lived strain of mouse, which basically means mice that live about three years on average. We do exactly nothing to them until they're already two years old. And then we do a whole bunch of stuff to them, and with those therapies, we get them to live, on average, to their fifth birthday. So, in other words, we add two years -- we treble their remaining lifespan, starting from the point that we started the therapies.
At'here, me ne fund do te shpenzoj pjese tjeter te fjalimit, shtate minutat e fundit, ne fazen e pare; domethene, se mund faktikisht te arrijm ne kete shtese te jetegjatesise kjo do na mundesoj te arrijn tek "escape velocity"? Dhe ne menyre qe te bejm kete, me duhet te flas rreth minjve per pak. Une kam nje perteritje te fuqishme te njeriut, perkatesisht nje monument historik. Une do ta quaj perteritje e fuqishme e miut, jo shume imagjinate. Dhe ja cfare eshte. Une them se do te marrim nje lloj miu jetegjate, e cila domethene minjt te cilet jetojn mesatarisht tre vjec. Ne nuk do bejm asgje me ta derisa te arrijn dy vjec. Dhe pastaj bejm shum gjera me ta, dhe me keto terapi, i bejme qe ata te jetojne, mesatarisht, deri ne pese vjec. Me fjale te tjera do ti shtojm dy vite jete -- ne ia shtojm jetegjatesine, duke filluar nga pika kur filluam terapine.
The question then is, what would that actually mean for the time frame until we get to the milestone I talked about earlier for humans? Which we can now, as I've explained, equivalently call either robust human rejuvenation or longevity escape velocity. Secondly, what does it mean for the public's perception of how long it's going to take for us to get to those things, starting from the time we get the mice? And thirdly, the question is, what will it do to actually how much people want it? And it seems to me that the first question is entirely a biology question, and it's extremely hard to answer. One has to be very speculative, and many of my colleagues would say that we should not do this speculation, that we should simply keep our counsel until we know more.
Pyetja eshte, cfare do te thote kjo per afatin kohor derisa te arrijm tek monumenti historik qe fola pak me pare per njerezit? Tani mundemi, ashtu sic e shpjegova, barazvlefshmerisht ta quajme ose perteritje e fuqishme e njerezve, ose "longevity escape velocity". Se dyti, cfare do kuptimi ka ne perceptimin e publikut sesa kohe do te na duhet te arrij tek keto gjera, duke filluar nga koha kur marrim miun? Dhe se treti, pyetja eshte, cfare do t'i bej faktit se sa shum njerezit e duan? Dhe sipas meje pyetja e pare eshte komplet pyetje biologjike, dhe eshte ekstremisht e veshtire per t'u pergjigjur. Duhet te jesh shume teorik, dhe shume kolege te mi do te thonin se nuk duhet ta bej kete meditim, thjeshte duhet ta ruajm konsullimin tone deri sa te dime me teper.
I say that's nonsense. I say we absolutely are irresponsible if we stay silent on this. We need to give our best guess as to the time frame, in order to give people a sense of proportion so that they can assess their priorities. So, I say that we have a 50/50 chance of reaching this RHR milestone, robust human rejuvenation, within 15 years from the point that we get to robust mouse rejuvenation. 15 years from the robust mouse. The public's perception will probably be somewhat better than that. The public tends to underestimate how difficult scientific things are. So they'll probably think it's five years away. They'll be wrong, but that actually won't matter too much. And finally, of course, I think it's fair to say that a large part of the reason why the public is so ambivalent about aging now is the global trance I spoke about earlier, the coping strategy. That will be history at this point, because it will no longer be possible to believe that aging is inevitable in humans, since it's been postponed so very effectively in mice. So we're likely to end up with a very strong change in people's attitudes, and of course that has enormous implications.
Une them se kjo s'ka kuptim. Une them jemi komplet te papergjegjshem nese qendrojm pa folur rreth kesaj. Ne duhet te japim me hamendje se ne cilin afat kohore, ne menyre qe t'iu japim njerezve domethenie se kur ata mund t'i diskutojn prioritetet e tyre. Keshtu qe une do te thoja se ka 50/50 mundesi te arrijm kete RHR eveniment historik, "RHR", brenda ketyre 15 viteve do mund te zgjasim jetegjatesine e minjve. 15 vite pas zgjatjes se minjve. Perceptimi i publikut me siguri do te jete me permiresuar. Publiku priret ta nenvleresoje sesa e veshtire eshte shkenca. Keshtu qe ata me siguri do mendojne se eshte pese vjet nga tani. Ata do jene gabim, por faktikisht s'do ket shum rendesi. Perfundimisht, mendoj se eshte e drejt te them sepse nje arye shume e fort perse publiku eshte kaq i ndare rreth moshes tani eshte nje trance global per te cilin fola me heret, perballimi strategjik. Kjo do behet histori ne kete pike, sepse nuk do te besohet se evitimi i plakjes tek njerezit nuk eshte e mundur, perderisa eshte shtyre me kaq efikasitet tek minjt. Keshtu qe do te shohim nje ndryshim te madh ne sjelljen e njerezve, dhe sigurisht kjo do kete pasoja te medha.
So in order to tell you now how we're going to get these mice, I'm going to add a little bit to my description of aging. I'm going to use this word "damage" to denote these intermediate things that are caused by metabolism and that eventually cause pathology. Because the critical thing about this is that even though the damage only eventually causes pathology, the damage itself is caused ongoing-ly throughout life, starting before we're born. But it is not part of metabolism itself. And this turns out to be useful. Because we can re-draw our original diagram this way. We can say that, fundamentally, the difference between gerontology and geriatrics is that gerontology tries to inhibit the rate at which metabolism lays down this damage. And I'm going to explain exactly what damage is in concrete biological terms in a moment. And geriatricians try to hold back the sands of time by stopping the damage converting into pathology. And the reason it's a losing battle is because the damage is continuing to accumulate.
Ne menyre qe t'iu them se si do ti marrim keto minj, Do te shtoj dicka tek pershkrimi im per plakjen. Do te perdore kete fjale "dem" te paraqes keto gjera te ndermjetme qe shkaktohen nga metabolismi, qe shkakton patologjine. Sepse gjeja kritike rreth kesaj eshte, edhe pse demi shkakton vetem pathologji, demi ne vetvete shkaktohet vazhdimisht gjate jetes, duke filluar perpara se ne te lindim. Por nuk eshte pjese e metabolismit ne vetvete. Dhe kjo eshte me vlere. Sepse mund ta vizatojm perseri diagramen origjinale ne kete menyre. Mund te themi, rrenjesisht, diferenca midis gerondologjise dhe gjeriatrise eshte se gerondologjia mundohet te frenoj shkallen me te cilen metabolismi shkakton kete dem. Dhe une do te shpjegoj eksaktesisht cfare demi eshte ne terma konkrete biologjike ne nje moment. Dhe gjeriatricianet mundohen te frenojne kohen duke ndaluar demin e konvertimit ne patologji. Dhe aryeja eshte nje beteje e humbur sepse demi vazhdon te akumulohet.
So there's a third approach, if we look at it this way. We can call it the "engineering approach," and I claim that the engineering approach is within range. The engineering approach does not intervene in any processes. It does not intervene in this process or this one. And that's good because it means that it's not a losing battle, and it's something that we are within range of being able to do, because it doesn't involve improving on evolution. The engineering approach simply says, "Let's go and periodically repair all of these various types of damage -- not necessarily repair them completely, but repair them quite a lot, so that we keep the level of damage down below the threshold that must exist, that causes it to be pathogenic." We know that this threshold exists, because we don't get age-related diseases until we're in middle age, even though the damage has been accumulating since before we were born.
At'here eshte nje trajtin i trete, nese e shohim nga kjo ane. Mund ta quajme trajtimi inxhinierik, dhe une pretendoj se trajtimi inxhinierik eshte pjese e zgjidhjes. Trajtimi inxhinierik nuk eshte nderhyne ne asnje proces. Nuk nderhyne ne kete, apo ate proces. Dhe kjo domethene se nuk eshte nje beteje e humber, dhe eshte dicka qe eshte midis mundesive, sepse nuk perfshin permiresim apo evolim. Trajtimi inxhinierik thjesht thote, "Hajde te shkojme periodikisht te riparojm keto lloje te ndryshme demesh -- nuk eshte e nevojshme ti riparojm komplet, por ti riparojm goxha, ne menyre qe ta ruajm nivelin e demit nen pragun qe duhet te eksiztoj, qe e shkakton ate te jete patologjik." Ne e dime se ky prag eksizston, sepse nuk kemi semundje te lidhura me moshen derisa arrijne ne moshen e mesme, edhe pse demi ka qene duke u akumuluar perpara se te lindnim.
Why do I say that we're in range? Well, this is basically it. The point about this slide is actually the bottom. If we try to say which bits of metabolism are important for aging, we will be here all night, because basically all of metabolism is important for aging in one way or another. This list is just for illustration; it is incomplete. The list on the right is also incomplete. It's a list of types of pathology that are age-related, and it's just an incomplete list. But I would like to claim to you that this list in the middle is actually complete -- this is the list of types of thing that qualify as damage, side effects of metabolism that cause pathology in the end, or that might cause pathology. And there are only seven of them. They're categories of things, of course, but there's only seven of them. Cell loss, mutations in chromosomes, mutations in the mitochondria and so on.
Pse them se jemi ne diapazon? E pra kjo eshte e gjitha. Pika kryesore e ketij slidi eshte fundi i tij. Nese filloj te themi se cila copez e metabolismit jane te rendesishme per plakjen, do te rrinim ketu gjith naten, sepse i gjithe metabolizmi eshte i rendesishem per plakjen ne nje menyre apo tjeter. Kjo list eshte thjesht per ilustrim, eshte e pakompletuar. Lista ne te djathte gjithashtu eshte e pakompletuar. Eshte nje list e llojeve te patologjis qe jane te lidhura me moshen, dhe eshte thjesht nje liste e pakompletuar. Por une pretendoj se kjo liste ne mes eshte e kompletuar, kjo eshte lista e gjerave te cilat qualifikojn si deme, pasojat anesore te metabolizmit qe shkaktojn patologjine ne fund, apo qe mund te shkaktojn patologjine. Jane vetem shtate. Kategorizohen ne nje, por jane shtate te tilla. Humbja e qelizave, mutacione ne kromozome, mutacione ne mitokondrine e keshtu me rralle.
First of all, I'd like to give you an argument for why that list is complete. Of course one can make a biological argument. One can say, "OK, what are we made of?" We're made of cells and stuff between cells. What can damage accumulate in? The answer is: long-lived molecules, because if a short-lived molecule undergoes damage, but then the molecule is destroyed -- like by a protein being destroyed by proteolysis -- then the damage is gone, too. It's got to be long-lived molecules. So, these seven things were all under discussion in gerontology a long time ago and that is pretty good news, because it means that, you know, we've come a long way in biology in these 20 years, so the fact that we haven't extended this list is a pretty good indication that there's no extension to be done. However, it's better than that; we actually know how to fix them all, in mice, in principle -- and what I mean by in principle is, we probably can actually implement these fixes within a decade. Some of them are partially implemented already, the ones at the top.
Se pari, dua te argumentoj per kjo list eshte e kompletuar. Sigurisht, dikush mund te kete nje argument biologjik. Dikush mund te thot, "OK, nga cfare perbehemi ne?" Ne perbehemi nga qeliza dhe gjera midis qelizave. Si mund te akumulohet demi? Pergjigja eshte, molekula jetegjata, sepse nese nje molekul jeteshkurter i nenshtrohet demit, athere molekula shkaterrohet -- si nga shkaterrimi i nje proteine nga proteolysis -- athere demi ka ikur, gjithashtu. Duhet te jene molekula jetegjata. Keto 7 gjera jane pjese e diskutimit ne gjereondologji shume kohe me pare dhe ky eshte lajm i mire, sepse nenkupton se, jemi zhvilluar goxha ne bilogji keto 20 vite, fakti qe nuk e kemi shtuar listen eshte nje shenje se nuk ka per tu bere ndonje shtese. Megjithate, eshte me mire se kaq; faktikisht ne e dime si ti ndrecim te gjitha keto tek minjt, ne princip -- ajo cka nenkuptoj me princip eshte se, me siguri mund ti implementojm keto ndrecje kete dekade. Disa nga keto jane pjeserisht te implementuara, ato te sipermet.
I haven't got time to go through them at all, but my conclusion is that, if we can actually get suitable funding for this, then we can probably develop robust mouse rejuvenation in only 10 years, but we do need to get serious about it. We do need to really start trying. So of course, there are some biologists in the audience, and I want to give some answers to some of the questions that you may have. You may have been dissatisfied with this talk, but fundamentally you have to go and read this stuff. I've published a great deal on this; I cite the experimental work on which my optimism is based, and there's quite a lot of detail there. The detail is what makes me confident of my rather aggressive time frames that I'm predicting here. So if you think that I'm wrong, you'd better damn well go and find out why you think I'm wrong.
Nuk kam pasur kohe te diskutoj per to, por konkluzioni eshte se, nese ne mund te gjejme fondet e nevojshme per kete, at'here me siguri mund te zhvillojme nje rinim te fuqishem te minjve brenda 10 viteve, por duhet ta marrim seriozisht. Duhet qe vertet te fillojme te bejme perpjekje. Natyrisht, jane disa biolog ne audience, dhe dua t'iu pergjigjem disa pyetjeve qe ju mund te keni. You mund te jeni zhgenjyer nga ky fjalim, por thellesisht ju duhet te shkoni dhe te lexoni keto gjera. Une kam publikuar shume rreth kesaj; I citoj eksperimentet ku optimizmi im bazohet, dhe ka shume detaje aty. Detajet jane ato qe me krijojne mua vetebesim te prashikimeve agresive te afateve kohore ketu. Pra, nese mendoni se jam gabim, Duhet te shkoni dhe te gjeni perse une jam gabim.
And of course the main thing is that you shouldn't trust people who call themselves gerontologists because, as with any radical departure from previous thinking within a particular field, you know, you expect people in the mainstream to be a bit resistant and not really to take it seriously. So, you know, you've got to actually do your homework, in order to understand whether this is true.
Dhe sigurisht kryesorja eshte qe nuk duhet ti besoni njerezit qe e quajne veten gjerendolog sepse, si cdo largim radikal nga nje mendim i meparshem rreth nje fushe te caktuar, pret qe njerez ne qender te jeni rezistent dhe nuk duhen marre seriozisht. Keshtu qe duhet ti besh detyrat e shtepise, ne menyre qe te kuptosh nese kjo eshte e vertete.
And we'll just end with a few things. One thing is, you know, you'll be hearing from a guy in the next session who said some time ago that he could sequence the human genome in half no time, and everyone said, "Well, it's obviously impossible." And you know what happened. So, you know, this does happen. We have various strategies -- there's the Methuselah Mouse Prize, which is basically an incentive to innovate, and to do what you think is going to work, and you get money for it if you win. There's a proposal to actually put together an institute. This is what's going to take a bit of money. But, I mean, look -- how long does it take to spend that on the war in Iraq? Not very long. OK. (Laughter) It's got to be philanthropic, because profits distract biotech, but it's basically got a 90 percent chance, I think, of succeeding in this. And I think we know how to do it. And I'll stop there. Thank you. (Applause)
Dhe do ta mbyllim me disa gjera. Do te degjoni nga dikush qe do vije ne seksionin tjeter i cili tha kohe me pare se mund te rendiste gjenomin e njeriut per pak kohe, dhe te gjithe thane, "E pra, eshte e pamundur." Dhe ju e dini se cfare ndodhi. Keshtu qe kjo ndodh. Ne kemi disa strategji -- eshte Methuselah Mouse Prize, e cila eshte ne themel nje shperblim per te motivuar, dhe te besh ate qe ti mendon se do te funksionoje, dhe merr para nese fiton. Eshte nje propozim qe te krijohet nje institute. Kjo do te kishte shume shpenzime. Sa kohe do te merrte ta shpenzoje ate ne luften e Irakut? Jo shum kohe. OK. (Buzeqeshje) Duhet te jet filantropike, sepse fitimet e hutojne biotech, por ne parim ka 90 perqind shanse, mendoj une, qe te jemi te suksesshem. Dhe mendoj se dime sesi ta bejm. Dhe do ndaloj aty. Faleminderit. (Duartrokitje)
Chris Anderson: OK. I don't know if there's going to be any questions but I thought I would give people the chance. Audience: Since you've been talking about aging and trying to defeat it, why is it that you make yourself appear like an old man? (Laughter)
Chris Anderson: OK. Nuk di nese keni ndonje pyetje por mendova t'iu jap njerezve nje shanse. Audienca: Meqenese ke folur per plakjen dhe si mund ta mposhtim ate, perse e ben veten te dukesh si nje plake? (Buzeqeshje)
AG: Because I am an old man. I am actually 158. (Laughter) (Applause)
AG: Sepse une jam nje plake. Jame ne fakt 158 vjece. (Buzeqeshje) (Duartrokitje)
Audience: Species on this planet have evolved with immune systems to fight off all the diseases so that individuals live long enough to procreate. However, as far as I know, all the species have evolved to actually die, so when cells divide, the telomerase get shorter, and eventually species die. So, why does -- evolution has -- seems to have selected against immortality, when it is so advantageous, or is evolution just incomplete?
Audience: Speciet e planetit kane evoluar me sistemi imunitar, per te luftuar te gjitha semundjet ne menyre qe individed te jetojn mjaftueshem per te ri-krijuar. Megjitheate, aq sa une jam ne dijeni, te gjitha qeniet evolojn per te vdekur, kur qelizat shumefishohen, telomerase behet e shkurter, dhe speciet vdesin. Athere, perse -- evolucioni -- duket sikur ka zgjedhur kunder pavdekshmerise, kur eshte kaq avantazhuese, apo eshte evolucioni i pakompletuar?
AG: Brilliant. Thank you for asking a question that I can answer with an uncontroversial answer. I'm going to tell you the genuine mainstream answer to your question, which I happen to agree with, which is that, no, aging is not a product of selection, evolution; [aging] is simply a product of evolutionary neglect. In other words, we have aging because it's hard work not to have aging; you need more genetic pathways, more sophistication in your genes in order to age more slowly, and that carries on being true the longer you push it out. So, to the extent that evolution doesn't matter, doesn't care whether genes are passed on by individuals, living a long time or by procreation, there's a certain amount of modulation of that, which is why different species have different lifespans, but that's why there are no immortal species.
AG: I madh je. Te falenderoj qe me bere nje pyetje qe mund ti pergjigjem me nje pergjigje te pakundershtueshme. Une do t'i pergjigjem me ciltersi dhe me pergjigjen e zakonshme, me te cilen une jam dakort, e cila eshte, jo, plakja nuk eshte produkt i selektimit, evolucion; [plakje] eshte thjesht nje produkt i neglizhimit te evolucionit. Me fjale te tjera, ne kemi plakjen pasi duhet shume pune mos ta kemi ate; te duhet me shume rruge gjenetike, me shume gjene te sofistikuara ne menyre qe te plakesh me ngadale dhe kjo vazhdon te vertetohet kur ne e nxjerrim ne pahe. Pra, perforcoj se evolucioni nuk ka rendesi, nuk me intereson nese gjenet vijne nga individed, te jetosh nje kohe te gjate apo nga pjelloria, ajo eshte e rregulluar ne nje sasi te caktuar, ja pse specie te ndryshme kane jetegjatesi te ndryshme, por prandaj nuk ka specie te pavdekshme.
CA: The genes don't care but we do?
CA: Gjeneve nuk iu intereson por neve po?
AG: That's right.
AG: Kjo eshte e vertete.
Audience: Hello. I read somewhere that in the last 20 years, the average lifespan of basically anyone on the planet has grown by 10 years. If I project that, that would make me think that I would live until 120 if I don't crash on my motorbike. That means that I'm one of your subjects to become a 1,000-year-old?
Audience: Pershendetje. Kam lexuar diku se ne 20 vitet e fundit, jetegjatesia mesatare ne planet eshte rritur me 10 vjet. Sipas kesaj une projektoj, se do te jetoj deri ne 120 vjec nese nuk pesoj aksident me motor. Kjo do te thot se une do te jem nje nga subjektet e tua per tu bere 1000 vjec?
AG: If you lose a bit of weight. (Laughter) Your numbers are a bit out. The standard numbers are that lifespans have been growing at between one and two years per decade. So, it's not quite as good as you might think, you might hope. But I intend to move it up to one year per year as soon as possible.
AG: Nese humb pak ne peshe. (Buzeqeshje) Llogaria juaj nuk eshte e sakte. Numrat standard thone se jetegjatesite kane ardhur duke u rritur 1 ose 2 vjet per dekade. Keshtu qe nuk eshte aq mire sa ju mendoni -- apo shpresoni. Por une planifikoj ta rrise nje 1 vit per cdo vit sa me shpejt te jet e mundur.
Audience: I was told that many of the brain cells we have as adults are actually in the human embryo, and that the brain cells last 80 years or so. If that is indeed true, biologically are there implications in the world of rejuvenation? If there are cells in my body that live all 80 years, as opposed to a typical, you know, couple of months?
Audience: Me kane then se shume prej qelizave te trurit qe kemi si adult ndodhen ne embrionin e njeriut, dhe qelizat e trurit zgjasin 80 vjet apo dicka e till. Nese kjo eshte e vertete, biologjikisht a do te kete implikacione ne boten e rinimit? Nese ka qeliza ne trupin tim qe jetojn vec 80 vjet, ne kundershtim me disa muaj?
AG: There are technical implications certainly. Basically what we need to do is replace cells in those few areas of the brain that lose cells at a respectable rate, especially neurons, but we don't want to replace them any faster than that -- or not much faster anyway, because replacing them too fast would degrade cognitive function. What I said about there being no non-aging species earlier on was a little bit of an oversimplification. There are species that have no aging -- Hydra for example -- but they do it by not having a nervous system -- and not having any tissues in fact that rely for their function on very long-lived cells.
AG: Do te kete implikime teknike, sigurisht. Ne themel, ajo cka duhet te bejme eshte ti zevendesojme qelizat ne ato pjese te trurit ku humbasin qelizat me shkalle te larte, sidomos neuronet, por nuk duam ti zevendesojm ato me shpejt se aq -- ose jo shume shpejt gjithesesi, sepse duke i zevendesuar ato shum shpejte do te degradonte funksionet njohese. Ajo c'ka thashe me heret se nuk ka specie qe nuk plaken ishte shume e thjeshtezuar. Ka specie qe nuk plaken -- Hidra per shembull -- por e bejne kete pa patur nje sistem nervor -- dhe pa patur ndonje organ qe varet nga funksionet e tyre ne cdo qelize jetegjate.