Daniel Lemire's blog

, 19 min read

Aging is a software bug

In my review of the movie Tomorrowland, I alluded to the fact that in the alternate world, people could stay young by drinking orange juice every morning. I conjectured that this was probably caused by nanotechnology.

I do not expect to ever drink some orange juice that keeps me young… but wouldn’t that be nice?

Someone accused me of being a follower of Ray Kurzweil. I had vaguely heard of Kurzweil as someone who advocates that, soon, computers will exceed the computational power of the human mind. Seems reasonable enough to me.

In any case, I went back and read some of Kurzweil’s work. It turns out that he does predict the arrival of nanotechnology-based rejuvenation. He even put a date to it: in 20 years, or around 2035. And after that point, forever youth could become reality.

One should point out that we cannot really defeat death. The best we could do is defeat aging: death as the result of an accident or a new disease is really hard to prevent, even in theory.

I do not believe that, currently, there is much you can do to extend your lifespan beside the usual if you are already healthy: keep your weight in check, exercise, have a loving family, don’t get mad at your collaborators… So, if you are healthy, do not bother looking for some magical orange juice. It is also not going to be easy to drastically extend our lifespan. If there was some simple herb that could rejuvenate us, the word would have gotten out by now. Moreover, if you could just flip a gene and live forever, we would have documented cases by now: there are billions of us… it is likely that one of us would have gotten the lucky mutation.

But Kurzweil believes that human technology is much stronger than mere luck.

By 2035, Kurzweil will have far exceeded men’s life expectancy (he will get close to 90). He has a plan to get there by closely monitoring his health and taking a crazy amount of supplements. That does not sound insane: if someone puts his mind to it, I am not sure why he cannot drastically increase his probability of living till late in his 80s.

Back to his predictions. It is evident that the rate of progress grows every year. If you must have a metric, look at the number of research articles published every year: it has consistently grown by more than 2% a year for as far back as I can look. By a small but consistent growth of about 3.5% a year, we went (in the US alone) from 110k medical research papers a year in 1996 to 200k in 2013. (This does not account for the fact that China hardly published anything in 1996 while it published 50k medical papers in 2013.) We get such progress because our tools get better and relatively cheaper every year while our collective expertise grows. Kurzweil says that to predict the amount of progress we shall make in the next 20 years, we must not simply project the progress of the past on the future, but rather multiply it. The farther you look, the wider the gap grows between a linear and exponential prediction.

Progress is necessarily unequal. Though we publish more medical papers every year than we ever did, some topics remain poorly researched whereas others are progressing much faster. But with an aging population worldwide, it is a safe bet that aging research is growing faster than medical research at large.

If you are not following closely biotechnology, it is easy to think that there is no much progress. But did you know that we have a relatively safe tool to edit human being genes called CRISPR since 2012? In fact, Chinese researchers are editing the genome of human embryos right now, hoping to prevent diseases. It is a safe bet that someone will soon attempt to raise “super human beings”: e.g., we already know of genetic mutations providing the recipients with superhuman muscles and unbreakable bones, an army of such people sounds like a tempting proposition. At Harvard, they are using this technology, as we speak, to turn an elephant into a mammoth by editing its genes. Did you know that we have commercially available bio 3D printers that can print skin or blood vessels? There is currently a competition to build an artificial liver good enough to keep a large animal alive for 90 days without any support: the competition ends in 2018. If the prize is won, and it will probably be, the next step is to create the other organs. At this rate, it is not hard to believe that, within ten years, we shall be technically able to replace any organ in one’s body, without any need for a human donor or for long-term dangerous medications.

Still. I have looked at Kurzweil predictions a bit more closely, and they seem a bit overoptimistic. I would say that you should probably add 10 years to all his dates. So, if Kurzweil was to predict that we would defeat aging in 30 or 40 years (in 2045 or 2055), then I would say that this is credible. If we go back 40 years ago, medicine was far, far less advanced. The rate of deaths from major diseases was often twice what it is today. If we project in the future several times the progress of the last 40 years, it is hard to imagine what we cannot do.

There is a problem with these predictions, of course. At the moment, we do not even know what aging is. Not really. We know that lobsters and naked mole rats do not age (they die but not because of an aging process similar to ours). The jellyfish and hydra are “immortal”. Some trees, like the bristlecode pine also do not age. Trees do not appear to age, or rather they age in reverse (getting stronger and more fertile with time), but are physically limited over time by their size (not unlike lobsters). We know that among creatures of the same size, say a mouse and a bat, there can be vast difference in longevities. Different species of sea urchins have reported lifespans ranging from 4 to more than 100 years. For individuals of the same species, big (or taller) individuals live shorter lives. We also know that if you inject the blood plasma of a young mouse in an old mouse (a technique called parabiosis), it rejuvenates the old mouse. But I do not think scientists can explain any of it (not to my satisfaction).

There are various theories about what aging is. Some say it is programmed. We are programmed to age. It does make sense from an evolutionary perspective that we are “programmed” to die after a time. And certainly, women are programmed to reproduce before the age of 40, but not after. This is probably well motivated: e.g, people who die make room for new people with possibly better genetic code… Another theory is that evolution did its best to maximize our lifespan, and we have the very best we can get… short of becoming androids. But there is no reason to believe that evolution would seek to maximize our lifespan. The cycle of birth, reproduction and death works well for evolution. Evolution does not care for the individual, only for the species.

I have also revisited Aubrey de Grey who has this ambitious plan to defeat aging using advanced regenerative medicine. He believes that aging is the result of “accumulated damage”. To him, our bodies are like rusting cars. Evidently, our bodies break down as they age… but why would a mouse accumulate damage 30 times faster than a human being? Why would it accumulate damage 8 times faster than a bat? And how come a whale or a turtle can live much older than us: aren’t they damaged? Some of aging is definitively accumulated damage… your teeth become shorter as you grow older, you accumulate latent viruses, fat cells, you lose neurons in the neocortex (and, in human beings, they are not replenished)… but male baldness is not a random outcome due to damage. Working out damages your body, yet it also improves your health, even in old age. This means that your body does not activate all of its self-repair mechanisms.

So aging is not solely a matter of “damage” (as in an old car). That is not to say that de Grey is wrong… I believe that he is right and I have given out some of my own money to his foundation. But I am not sure the analogy between a car and the human body is best. My own theory, after reading avidly on the topic for several days, is that we are like a piece of software designed in 1970 and still running three decades later… we are hitting various “year 2000 bugs“. Evolution did not try to maximize our life expectancy (as it may have done with turtles and some whales). If anything, evolution is glad we do not often live beyond 90.

It seems to me that the easiest way to live longer would be to hack our own software (our genome, our biome) as well as repairing various sources of damages (e.g., using stem cells). Sadly, as I have pointed out, it cannot be a simple matter of turning on one gene or the other. Software programmers know all too well how hard it can be to fix what might appear like a minor adjustment… Some bugs can be fixed by changing a few lines, but some require rewriting entire code segments. To turn the clock, we will need some fancy engineering. What is this clock? There is some hope that the clock in question could be our telomeres. It is an apparently frivolous part of your DNA that grows shorter with every cell division. So it would seem like simply making the telomere longer could make us somewhat younger again. Thankfully, we know how to do just that using telomerase. De Jesus et al. showed that telomerase gene therapy in old mice delays aging and increases longevity without increasing cancer. So, maybe, if we could replenish our telomeres without killing ourselves, we could fool our body into thinking it is younger. It seems that people who live very old without cancer or Alzheimer’s are more likely to have a rare mutation that activates telomerase production. But there is no guarantee that it would work. For one thing, some cells do produce telomerase (e.g., the white cells) and their telomeres still grow short in some people. For another, we know that some cells rarely multiply and are thus unlikely to be limited by telomeres (e.g., your neurons). Moreover, eating well and exercising can extend your telomeres in some cells, though it evidently does not make you younger. There are other possible biological clocks such as DNA methylation. We really do not know enough about what makes a cell old!

It is not just your cells that get old. The tissues themselves (like your skin) fail to repair themselves properly with age. You can see wrinkles in people over 40. We also accumulate lots of broken protein that go on to contribute to Alzheimer’s, Parkinson’s and plenty of other diseases.

Still, I believe that telomeres elongation of some specific cells (with or without telomerase) coupled with advanced stem cell therapy and/or a few well-dosed hormones and proteins could probably rejuvenate you, maybe. For example, a simple, freely available, hormone, oxytocin can rejuvenate muscles. But it is also possible, even likely, that it is much more complicated, even assuming that I got everything right.

So it could easily take 500 years to defeat aging. The point is, we will defeat aging eventually… After all, we can already extend the lifespan of monkeys by reducing nearly by half their rate of death.

One can dream. I imagine that, in the future, you will live normally as human being until you are about 40 (when reproduction normally stops) at which point, you will start taking pills, or injections or nanobots, to make your body believe that you are still 30. There will be some wear and tear, as indicated by de Grey, but it won’t be a big problem. Using 3D printers, we shall be able to print new body parts out of our stem cells. Or, better yet, we will get in situ regeneration. You would need to replenish the neurons in your neocortex every few decades.

When that happens, be ready to work for 60 years or more! (Assuming that people still need to work in the future…)

Unfortunately, there seems to be less research on this important question that you may think. For example, there is a compound that is FDA approved (rapamycin) that is believed to extend lifespans of mammals through some gene hacking. Since we are already giving it to some human beings, you would think that we would have tested it on all mammals by now. Sadly no. There is a project to use it on dogs however, but I do not know whether they got funded.

(Do not go out on the black market to buy rapamycin. It has nasty side effects and it would, at best, delay aging… not reverse or stop it. Plus, it appears to be a telomerase inhibitor so it could actually make your telomeres shorter… and give you cancer and diabetes…)

Unfortunately, we will not defeat aging in the next ten years I would think (short of a surprising, 1 in a million, breakthrough). For one thing, “defeating aging” is not yet a socially acceptable goal. It is a taboo. We do not know what aging is. We have no proven means right now to extend human lifespan. You can probably help your chances of making it to 80, but there is nothing you can do to get beyond 125.

To have any realistic chance at defeating aging in ten years, we would need to have done it, right now, in a few people or in a mouse. To have a realistic chance of doing it in 20 years, we would need to have an excellent plan right now. Maybe someone has such a plan right now… it is hard to tell… given the profit involved, they might not freely share their plan… de Grey has such a plan, but he will only commit to a 25-year schedule on the condition that he has a billion dollars… yet he does not have a billion dollar.

But there are reasons to be hopeful. Google, of all places, created a company with the express goal of extending our healthspan by 20 to 100 years: Calico. It is not just a silly thing: they have recruited the best scientists that money could buy. Calico has hundreds of millions of dollars with commitments exceeding a billion dollars. Calico is hardly alone: Unity Biotechnology is another well-funded technology company that seeks to “cure aging” (it is backed by Amazon’s CEO) . If you want to be optimistic, you could imagine that Calico or some other laboratory could have, right now, a viable plan to put a dent in aging. If, they could be testing it in human beings in 20 years, and it could be ready for the rest of us in 30 years.

So, let me come up with a prediction: we will defeat aging in 40 years. By that I mean that age-related disease would be mostly under control, if not outright eliminated. So maybe you still get Alzheimer’s or a heart condition, but medical therapies are so good that you can go on living a happy and productive life. Compared to Kurzweil, I am pessimistic (he predicts 20 years or less.)

Speaking for myself, I expect to be dead in 40 years… if nothing changes. I do not think any man in my family has made in his eighties… So if I do not die of something else first, I can expect to die from an age-related disease in my seventies or sooner: cancer, Alzheimer’s, heart attack… Even if I were to survive that long, I fear I would be severely diminished… There is, however, a small probability that I could have a very different life. For one thing, maybe Kurzweil is right and we will defeat aging in 20 years. I stand a good chance of making it there. That sounds much too optimistic however.

But there is another intriguing possibility popularized by Kurzweil and de Grey. Suppose that we defeat aging layer by layer. Imagine that, in five years, we find a way to rejuvenate old people by 3 years… and then, ten years later, by 5 years… and then ten years later by 7 years… if this were to happen, I am much more likely to make it to my eighties. And by then, it is much more likely that they will be able to reverse my aging. This concept is sometimes called the longevity escape velocity: you do not need to live long enough to see a cure for aging, you just need to live long enough to see partial progress. Partial progress is much easier than defeating entirely aging. When we will understand better age-related gene expressions, we might be able to tune your “epigenetics” so that it is more youthful simply with a few injections. After all, if parabiosis works, it seems pretty clear that with the right doses of drugs, we could simulate the same effect without requiring a young person’s blood. Such an approach could buy all of us a few extra years. Then if we improve stem cell technology significantly, we might be able to undo other age-related damages. And then maybe we could find a way to elongate our telomeres… after all our body knows how to do it, it simply chooses not to. Successive waves of progress could add up in such a manner.

I have a really hard time imagining that we will still grow old 500 years from now. I do not have a lot of faith in biologists, but there are many of them and they have better and better tools.

But here is something interesting: we never imagine a future where people do not grow old. In Star Trek, James T. Kirk grows old. Even the fierce Vulcans grow old. In Star Wars, people grow old. The only science-fiction author who represented fairly, in my mind, what could happen as we defeat aging through technology is Peter F. Hamilton in his Commonwealth Saga (starting with Pandora’s Star).

We still grant public employees pension plans based on limited longevities. There is a very serious risk that we are grossly underestimating the life expectancy of 20-year-old employees. As far as I can tell, this is never discussed.

I believe that it is because defeating aging by technology is a taboo. Not even science-fiction writers want to consider it. In a sense, it is not surprising that only a few outliers like de Grey and Kurzweil talk about it. Sure, they are probably wrong in many important ways… but they are not wrong in the way that matters: aging can and will be defeated. I expect it is simply a bug in our software: we can reengineer our bodies so that they do not age. You may have to walk around with nanobots in you, but you will not age as long as you are careful.

Let me conclude by quoting Richard Feynman (one of the greatest scientists of the XXth century):

It is one of the most remarkable things that in all of the biological sciences there is no clue as to the necessity of death. If you say we want to make perpetual motion, we have discovered enough laws as we studied physics to see that it is either absolutely impossible or else the laws are wrong. But there is nothing in biology yet found that indicates the inevitability of death. This suggests to me that it is not at all inevitable and that it is only a matter of time before the biologists discover what it is that is causing us the trouble and that this terrible universal disease or temporariness of the human’s body will be cured.

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