The Quest for Indefinite Life I:
Engineered Negligible Senescence

Aubrey de Grey
Issue XXIV - July 29, 2004
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What is Engineered Negligible Sensecence?

"It's not a very catchy name, is it?" you may be thinking.

Yes, I know -- "Engineered Negligible Senescence" has ten syllables and is not the world's most memorable, or indeed self-explanatory, phrase. But it is a good name for our ultimate goal, honest -- as well as SENS being a catchy acronym. Here's an explanation. I'm afraid it starts with a rather long preamble, but trust me, it's worth it.

First, let's be precise: our ultimate goal is the availability to the entire human race of technology that will restore them to whatever degree of youth they desire and keep them there for as long as they want. That's a bit stronger than simply "a cure for aging" -- it says that the cure should be available (at a price that they can afford, of course) to absolutely anyone who wants it.

But then, what does "youth" mean? I don't think many 70-year-olds will want therapies that erase all the knowledge that they've gained in the second half of their life, for example, nor their taste for music that is eschewed by the younger generation. No -- what "youth" means for our purposes is physical robustness and vitality.

That's where things get tricky. We know aging when we see it, but it is actually very hard indeed to measure .... until it's over. It isn't very hard to distinguish a dead person from a live one, but telling the difference (accurately, mind -- not just 70% of the time) between a person who's likely to live another 10 years and one who's likely to live another 20 is very much harder. We have one very approximate measure of how long someone's likely to live, namely how long they've lived already, and even though scientists have tried very hard they have so far failed to find an appreciably better one.

But this isn't as hopeless as you might think. We can say, very clearly, that loss of physical robustness and vitality is what kills most of us (those that don't die of homicide and such like). It makes us less resistant to diseases like flu that we can fight off easily in our earlier years. It makes us more likely to break bones if we fall, and those breaks take longer to heal, so we have to stop exercising, so we get even more susceptible to diseases. It slows our reactions, so that when we slip on the stairs we can't catch ourselves, so we fall, etc. So actually, aging and death are more closely linked than they might be. People who are physically robust are not likely to die any time soon; people who are physically frail are more likely to die soon.

There are two consequences of this. One is that the goal that a lot of biogerontologists (who should know better) advocate as the ultimate purpose of their work is totally impossible (even if it were desirable, which is unclear). That goal is often called "compression of morbidity", and what it means is a shortening of the average length of time that people spend in a frail state before they die. The idea is that we should not be trying to extend total lifespan, only healthy lifespan ("healthspan"). As you can see, the only way to do that is to limit access to medical care for things that people tend to die suddenly of, such as heart failure, so that fewer of us die of lingering diseases like cancer. And society, surprise surprise, seems dubious about that strategy -- or, indeed, any other strategy that shortens people's average total lifespan.

The other consequence of the tight biological linkage between aging and death is that we can measure our ability to combat aging by observing our impact on death rates, and this is where I (finally!) get to explain the basis for the term "Engineered Negligible Senescence".

Let's start at the end, with "senescence". This is a term that many biogerontologists have used for a very long time, and informally what they mean by it is the progressive loss of physical robustness that happens with time. But because of the linkage between aging and death, they have also been able to give "senescence" a formal, mathematical definition -- the progressive increase in an organism's likelihood to die soon. This is something that can be measured. It can't be measured on a single individual, because single individuals only die once and that single event doesn't give much information about how likely the person was to die at any prior time (or, indeed, at any later time if they hadn't died when they did). But if we look at a population of people (or other organisms, for that matter), we have a lot of information -- the age at death of each individual -- and we can use that to estimate the probability of death. In particular, we can use it to relate the probability of death to other characteristics of the individuals, such as their diet, their gender -- or their age. This is what gerontologists have done: they have defined the term "senescence" to mean a positive correlation between age and risk of death.

To see what this means in practical terms, think about radioactivity. We can talk about the half-life of a radioactive isotope, and indeed we can measure and state very very precisely what that half-life is. We do this by measuring the distribution of time of decay -- "death" -- of individual atoms in a sample of the isotope. And the point is, that half-life stays the same forever, even though atoms are decaying all the time. Each individual atom retains the exact same probability of decaying in the next hour (or second, or year -- it doesn't matter what unit of time you look at) as it had before, right up until the moment that it actually decays. In the language of biogerontology, radioactive atoms die but they don't senesce. People, on the other hand, do senesce, because the probability of a 70-year-old dying in the next year is higher than the probability of a 60-year-old dying in the next year.

But hang on -- how do we know that radioactive atoms don't senesce? There are, after all, only a finite number of atoms in the sample that we measure the decay of -- a very large number, but still it's finite. So in fact, if they senesce just a tiny tiny bit over time -- that is, if their half-life gets shorter, very very slowly -- we wouldn't actually be able to tell that this was happening in the time that we took our measurements, because the acceleration in the rate of atoms decaying (relative, of course, to the number that had not decayed already, which is always decreasing) would be too tiny to be statistically detectable. With finite numbers of events, we are always only able to say things with confidence if we restrict ourselves to talking about possible ranges in which a rate might fall. So here, we can only say that there is a range of possible rates of senescence of the radioactive sample, and if there is a really tiny rate of senescence, that range would still include zero.

This is not very interesting in radioactivity, because the number of atoms we look at is usually so huge that for practical purposes we can forget about the possibility of half-lives getting shorter. But in gerontology it matters a lot, because the number of people (or animals) that we can look at the ages at death of is relatively small. This was recognised some time ago, especially by a very eminent and innovative gerontologist named Caleb Finch. He introduced the term "negligible senescence" to mean "senescence too slight to be statistically distinguishable from zero with the sample sizes at our disposal". That includes non-senescence, of course -- truly zero correlation between age and risk of death -- but the point was that it encapsulated the experimental and observational reality that if we found a truly non-senescing organism, we could never truly know that we had done so. (Indeed, most biogerontologists believe that some organisms, even some very primitive animals, are non-senescing, but they can't prove it, and Finch made this explicit.)

Biogerontologists like the term "negligible senescence" for exactly this reason -- as scientists, they like to say what they know and no more. This of course means that they immediately understand the term "engineered negligible senescence" -- the biotechnological conversion of a population that shows senescence (humans, of course) into one that does not.

So that's why I have chosen to use the term "engineered negligible senescence" (ENS) to describe what I want to help develop, and why my work is therefore best described as the development of strategies for ENS, or SENS. I'm a biogerontologist myself, after all -- and, never forget, I consider my fellow biogerontologists to be my most important audience, because they are so powerful. If every expert in the biology of aging agreed with me about the foreseeability of ENS, my job would be essentially done: public opinion would fall in behind the scientists (as it always does), the political weight would fall in behind public opinion (as it always does), and the research and development would proceed as fast as possible, with no financial obstacles whatsoever. So I like to use a term that my colleagues in biogerontology understand well and are comfortable with, even if it may be a bit of a mouthful.

Why should you do whatever you can to expedite the defeat of human aging?

Because saving lives is the most valuable thing anyone can spend their time doing, and since over 100,000 people die every single day of causes that young people essentially never die of, you'll save more lives by helping to cure aging than in any other way. (Some people can make more difference than others, sure, but don't underestimate how much difference you can make: look here first, and also think hard about what you might be able to do that I don't mention there.)

The rest of this page is a rebuttal of some of the more common reasons people give for not buying the above argument. If you aren't convinced that I'm right by the time you leave this page, I encourage you to email me with your reasons. If you are convinced, email me too -- that way we can work together to make the best use of your talents (including, perhaps, improving or adding to the arguments presented on this page). Which means that if you don't email me, you think it's OK not to work to cure aging and it's also OK not to be able and willing to say why it's OK. Don't forget that.

"You're not talking about saving lives, you're talking about extending lives"

There's no difference between extending lives and saving lives. When we save someone's life, we give them the opportunity to live longer than they would otherwise have had the opportunity to live. Period. If you think you can state a clear-cut distinction between saving and extending someone's life, send me it. And don't forget that the life that rejuvenation therapies will allow is not one with extended frailty at the end of it, but one with no frailty, even at the end.

"I'm too old to have any chance of benefiting"

So what? Are your children too old? All lives are valuable. Consider the passengers on flight 93, who overpowered the hijackers. They can't have thought they had much chance of saving their own lives. They must have acted as they did because they knew they were going to save a great many lives on the ground. Did they know whose lives? -- clearly not. And they didn't care.

"It's more urgent to feed those who are starving today"

There are three errors in this idea. First, the question each of us must ask is how much difference we can make. Since the main problem with curing aging soon is getting the science done, the vast majority of people can make more difference to it than to starvation in the third world simply because the latter involves overpowering enormous political and economic pressures to preserve the status quo. Second, even if there were a choice between feeding the starving and curing aging, the arithmetic of healthy years added to people's lives by the two policies (see the last paragraph on this page) argues that we should put most of our effort into curing aging. But the third error is the most decisive: the idea that curing aging isn't urgent is based on the fact that it'll definitely take a couple of decades at least, whereas feeding the starving saves lives immediately. This is not logical. Consider two ways that someone (A) might kill someone else (B): A might shoot B, or A might build a house for B and purposely make the roof unsound so that it falls in and crushes B in bed a year later. The interval between A's action and B's death in these cases is different by perhaps seven or eight orders of magnitude, but is A's culpability any different? No. It's not different if B sells the house in the interval and the person who dies is C, either -- nor if by a fluke the roof falls in when there's no one home. So long as there is a pretty good chance that an action today will bring the cure for aging closer, that action today is saving lives.

"Curing aging is so far away that our actions today are irrelevant: serendipitous future discoveries will determine when aging is cured"

No short answer to this could be persuasive; my answer is strong by virtue of its attention to detail. To learn why I claim that we are likely to cure aging within 30 or so years if we start trying, see my detailed science pages, starting with this one.

"Overpopulation ... boredom ... only for the rich ... immortal tyrants"

There are two types of answer to these and other reservations about curing aging based on possible social consequences. One is to examine each such reservation in depth and construct a detailed argument for how we might avoid the scenario in question. I think that's a valuable approach; I adopted it myself here and many others have done the same, often better than me. But I also have a more general response, which among other things avoids objections of the form: "Well, yes, that's a strategy, but what if it fails?". Namely: pay attention, people -- we're talking about lives here, 100,000 lives a day. What do you do at the moment if you're bored? -- kill yourself? I didn't think so. Society has always had problems and doubtless always will, and it works to minimise and solve them, just like technological problems. Pretending that we will be so unable to cope with future problems that it's better to condemn indefinite billions to the puny lifespan of their ancestors is a sick joke anyway, but even sicker when we consider how implausible it is that such problems would be any worse or harder to tackle than those that we've tackled in the past. It's not as if the problems we have successfully tackled in the past seemed less daunting, either. For example, who would have thought in 1850 that society would be willing to submit to the indignity of wearing absurd rubber contraptions every time they had sex, just to arrest the population explosion that followed the near-elimination of infant mortality? Yet, that's just what happened throughout the industrialised world, with no coercion other than the simple fact that children who are still alive are very expensive.

One social argument is perhaps worth singling out, however: the idea that we would have difficulty paying all those retirement benefits. Retirement benefits are for frail people. There won't be any frail people. Also, people who still (or again) have the vitality that they had in their 20s and 30s will not want to play golf all day forever, even if we did have the money to let them do so. (This is not to say retirement will cease. Rather, it will be a voluntary, periodic thing -- maybe ten years every 50, two years every ten if you prefer.) This is one of the most tangible and unambiguous benefits of curing aging: far from being increasingly consumed by the elderly (as is happening with the pension situation today), wealth will be actually contributed to society by all people, of whatever age.

"Finitude gives life meaning .... the natural order is best"

This type of "ethical" argument is possibly the most absurd of all -- a strong statement, I realise, given the stiffness of its competition -- because of the enormity of what it overlooks within its own scope. To stand back and (by one's inaction) cause someone to die sooner, when one could act to let them live a lot longer at no (or even at some modest) cost to oneself or anyone else, is arguably the second most unnatural thing a human can do, second only (and then by a very small margin) to causing someone's death by an explicit action. (Of course, there is plenty of departure from these ethics in the world, but that's not the point -- abandonment of the law of the jungle is what most fundamentally defines humanity, and also what defines civilisation.) Thus, to ask humanity to accept the "naturalness" argument against life extension, and on that basis to delay the development of a cure for aging, is thus to ask it to transform itself into something as un-human as can be imagined. Even if such concerns were to turn out to be valid, it is for those who experience this diminution of their existence to act to restore it (e.g., by rejecting rejuvenation therapies that are on offer), not for us to make their choice for them.

"I do other things that save lives; I can't do both"

If you're saving lives at all, you're in a small minority; but before you reject the possibility that maybe it would be even better to cure aging, do some arithmetic. Saving of lives should really be measured not in number of lives extended but in aggregate number of life-years added. If you've seen my timeframes page you will know that I think people who are around long enough for serious rejuvenation therapies will live indefinitely: the cusp between the development of the first generation therapies and the attainment of "escape velocity" will be very brief indeed. Putting this in concrete terms, the first 1000-year-old is probably only five or ten years younger than the first 150-year-old. (The question we can't yet answer, but can influence, is how old they are today.) Also, let me emphasise again here that these extra years would be youthful -- our physical and mental functions would be maintained in as good a state as when we were young adults, right up to the time when we make a serious mistake crossing the road. Even if we don't become a lot more risk-averse as a result, that means such people will have a life expectancy (i.e., average age at death) of around 1000 years, by virtue of being only as likely to die in any given year as we currently are to die at the age of (say) exactly 12 if we don't die before that. So that means that if you accelerate the process of developing a cure for aging so that it happens even one day sooner, you'll add an average several hundred years to the lifespans of over 100,000 people -- so you'll be adding about 100 million person-years to people's lives. (It's worth stressing here that the same applies to work targeted to making rejuvenation therapies widely available as fast as possible once they are developed, which will be a lot more successful with a bit of forward planning.) And that's just one day; given the rather small number of people currently working actively to cure aging as soon as possible, each newcomer to the cause will surely do better than that, whatever their talents. Can you really come anywhere near that number in any other way?

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Learn about Mr. Stolyarov's novel, Eden against the Colossus, here.

Read Mr. Stolyarov's comprehensive treatise, A Rational Cosmology, explicating such terms as the universe, matter, space, time, sound, light, life, consciousness, and volition, here.

Read Mr. Stolyarov's four-act play, Implied Consent, a futuristic intellectual drama on the sanctity of human life, here.