Aging as a Problem

Warning: very long post. I try to outline the concept, value and current status of addressing human aging as a fixable biomedical problem. Would this destroy our society? Probably not.

Getting older is the single biggest risk factor for most scary diseases (cancer, heart disease, Alzheimer’s…)1. Such diseases, caused primarily by aging, kill about 32 million people per year, or 87 thousand people per day. The simple graph below compares this to the bloodiest conflict in human history, as well as the most violent incident of terrorism:

Aging kills

To be fair World War II didn’t involve the entire world, and total population was smaller back then. But the 3.5 fold scale should adequately balance that. Try to visualize WWII raging, people dying in agony; if there was a chance to end it, would that be worth trying? OK, Stalin may have had a valid point about millions of deaths being statistics rather than tragedies. But it’s not hard to spot tragedy caused by aging: aging will kill your parents, and will force your children to watch you grow senile and forget who they (or you) are. They will likely watch you in a hospital bed that eats away a BMW-sized chunk of their savings every month2, and when you are gone will feel the absence of one of the most important things in their lives.

Seeing aging as a problem is of course not new, and throughout history different people have tried different methods to avoid it. But the scientific method, which has been so rewarding for us modern humans, has only been applied to aging for perhaps sixty or eighty years. And in fact, in the last two decades researchers have been able to slow down the aging process through genetic manipulation, drugs and environmental factors3. Almost all such work happens in model organisms (mainly worms, flies and mice), because they allow genetic modification and have short enough lifespans to make controlled experiments possible. This lack of anthropocentrism should not discourage us, however, since the same is true for almost all biological research and drug development. We are in fact surprisingly genetically similar to other animals: even fruit flies have parallels for ~75% of genes involved in human disease, and the biological pathways are even more conserved in terms of function. Thus aging is now de facto a modifiable property of organisms, though this has yet to be properly demonstrated in humans.

Caloric restriction rhesus monkeys

Despite this progress in understanding and modifying the process of aging, there is no clear-cut definition of precisely what aging is. This is in large part because the symptoms of aging (such as wrinkles, or age-related diseases) are often conflated with the underlying biological process4. In the research community, one currently favored definition is “loss of the body’s capacity to return to homeostasis after environmental insult”. A more traditional definition might be “comprehensive and progressive decline of physiological function”, and this conveniently serves as a decent working definition to distinguish aging from specifics symptoms: does a given treatment alleviate a broad spectrum of symptoms, or just a few? And moreover, does it affect “normal” individuals, or only those suffering from a specific disease? Another reason we don’t have a clear definition is that we still don’t know exactly what causes the human body to decline with age. A number of theories have been proposed over the years: some have fallen by the wayside, while others remain popular despite evidence that they do not offer a complete explanation for the aging process (e.g. free radicals, or telomeres). More likely aging is multifactorial, although the different factors may converge on certain biological processes. Work is ongoing to identify measures of physiological age (as opposed to simple chronological age), of which DNA methylation has shown the best results so far.

Aging may seem universal because the animals we most commonly interact with (cats, dogs, livestock) go through much the same process as humans, albeit much faster. But there are many examples in nature of qualitatively different aging: tortoises can live much longer than humans, but more importantly their rate of mortality does not seem to increase over time. In other words they do age, but as far as we can tell they don’t undergo the same process of deterioration. Note that this doesn’t mean they never die, just that their probability of staying alive and healthy is constant year to year. This may also be true of lobsters, who also do not seem to lose fertility with age. Though less attractive, opposite examples also exist: salmon and octopi mature, reproduce and then die abruptly rather than undergoing a gradual decline. Perhaps more remarkably, aging is not strictly a unidirectional process: some members of the turritopsis and hydra genuses do grow old and decrepit, but are then able to return their entire body to a youthful state (here is an amusingly over-the-top story about them). Axolotl salamanders and planarian worms are famously able to regrow large parts of their bodies, which is a similar process of turning old cells into young ones. Indeed, from a biological rather than individual point of view, humans routinely perform the same feat: the egg of a middle-aged woman has the capacity to produce a complete human body where all signs of aging have been erased. Similarly, the 2012 Nobel Prize in physiology recognized the demonstration that any cell in our body can be turned into a stem cell. Rejuvenation is thus biologically possible in humans, though we are still far from understanding the barriers that keep it from happening in our adult bodies.

Long-lived animals

The media can sometimes make it seem as though there’s a focused effort by brilliant scientists to solve the problem of aging (and all other problems, for that matter). Unfortunately that’s far from true. The biogerontogical research community is growing, thanks in part to aforementioned progress, but is still very small. I don’t have actual numbers, but I would guess the number of researchers is on the order of thousands. That is, comparable to a single mid-sized company. As another way to size things up, the National Institute of Aging is by far the primary source of research funding in the US, and has a budget of just over a billion dollars. ~20% goes to non-research expenses, and about a third of the remainder to social and geriatrics research. So we’re left with ~0.6 billion dollars. This may sound like a lot, but it is only ~12% of the National Cancer Institute’s budget (even though aging is the biggest risk factor for cancer). The military budget is more than a thousand times larger, but perhaps more critically the total US healthcare spending is at least one hundred times the entire budget for biomedical research (of which the biology of aging is ~2%). This despite the fact that a huge proportion of the healthcare spending is due to age-related diseases2. I won’t discuss this allocation here, but simply emphasize that the cavalry is not on its way. A smallish number of researchers are working pretty hard, but regardless of their talent and effort scientific progress is not straightforward; the fact that you’re in unexplored territory inevitably implies many false starts and detours. With the current setup, real progress on avoiding the problems of aging is likely to be slow.

In summary: Negligible aging is biologically possible. Barring extinction of the human race, we will eventually turn the implausible-but-possible into reality, as we have for such miracles as flight, space travel and wireless communication. Whether this will happen in 50 or 5000 years is impossible to say for certain, because it depends both on our efforts and how many unknown unknowns we run into. At present only a minority of research is aimed at modulating the rate of aging itself, with the majority addressing individual age-related diseases or trying to understand specific cellular mechanisms that seem to be involved in aging. Some would argue that this should change, although such research is undeniably providing clues about aging itself. Regardless of allocation, more resources directed at this problem would unquestionably accelerate progress5.

But what if we were to get there? What if we developed technologies that eliminated disease and death completely. In reality there would never be such an abrupt switch, but rather a continued development of things that add a few months or years of healthy living (as we have already been doing throughout modern human history). Thus one common fear, that life extension would mean additional years of frailty and sickness, is rather unfounded; as a biologist, it’s simply inconceivable that we would continue to find ways to keep a profoundly broken organism alive. Modern medicine does have tools to sustain life at its very end, but although the emotional impact of these final days is great, the actual period of time is tiny compared to the added years granted by treating disease in mostly healthy individuals. Come old age and multiple morbidity, the effectiveness of treatments drops drastically. And indeed the premise of research into aging, rather than specific age-related diseases, is to slow down the process that causes such diseases and thus maintain the youthful state.

So we can rest assured that the fate of Tithonus is not a realistic consequence of aging research. And as I’ve addressed in another post, neither is overpopulation. So these common fears are actually not things we need to worry about. But of course there are a number of likely consequences from significant life extension, some desirable and others challenging.

The most obvious, perhaps to the point of under-appreciation, is that we would not suffer the loss of loved ones. But beyond the obvious, the vacuum left when someone passes away extends beyond personal loss; in the modern world, what you learn is indubitably a greater factor in your ability to contribute to society than is the infinitesimal genetic improvement that comes with being part of the next generation (in fact I would argue that genetic evolution is no longer applicable, but that’s a separate post). Particularly if we subscribe to the notion of combinatorial creativity, a person who continues to accumulate knowledge and is not subject to dementia or other debilitating effects of aging would perpetually and increasingly outpace even genetically superior persons that suffered from a complete knowledge reset every few decades.

And this effect of keeping everyone healthy and active would be on top of the direct healthcare savings that would follow from reducing, let alone eliminating, age-related disease and infirmity (recently estimated to be trillions of dollars, just from the effect of currently available drugs on animal models). It’s highly possible (and discussed elsewhere) that the current demographic trajectory will lead to the collapse of traditional retirement plans in the foreseeable future, which would evidently be alleviated by simultaneously preserving people’s ability to do useful work and reducing their demand for healthcare. But honestly this is a bit misleading, because if we did not age there would almost certainly not be a concept of ‘retirement’ involving indefinite cessation of productive work.

This is an example of something that would be a radical and not strictly positive change in a post-aging world. On the other hand, if we remember that we would not be ‘worn out’ at this age, it’s not necessarily strictly negative either: The basic premise would be the same as now, that we work enough to support periods of non-work. We would only be changing the timing and frequency of such periods (which some people already do). At present, it is very rare for people to have more than one or two careers; there simply isn’t enough time to get good at many things. But if “retirement” meant some years of complete separation from your profession without any acute loss of ability to support yourself, you might decide to go in a different direction upon reentering the ‘active work’ phase. Without physiological decline, you would be able to have as many or as few careers as you had appetite for. And here’s it’s worth noting that physiological decline is not limited to disease: Post-aging, we (women especially) would no longer need to balance the choice of parenthood against building career capital or pursuing other life goals. While I’m not qualified to offer personal experiences here, I would estimate having the option of raising children whenever it suited your lifestyle of inclination to be exceptionally liberating. And breaking the confines of our biology in this manner would empower more than reproduction: no longer would professional sports (or dance, or military service…) be the exclusive realm of people in the early stages of life.

Of course, opening up such possibilities would break some of the assumptions we currently make in social interactions. Unable to correlate wrinkles with wisdom, we would have to do a lot more research to discover other people’s situations and perspectives. There would likely be serious (or complete) dilution of recognizable ‘life stages’, and quite likely we would have fewer spontaneous instances of social groups with a shared identity (e.g. college). The ‘elders’ of a family would not be easily recognizable for outsiders, and without attrition families might expand indefinitely (albeit likely much slower). It’s hard to predict how our ties to blood relations separated by many decades of experience might feel.

Returning to more tangible issues, one challenge that would be alleviated by extended lifespans is that of absorbing the ever-increasing sum of knowledge in the world. In 1940, ~25% of Americans finished high school, <5% college. In 2014 those numbers were 88 and 32% respectively. Even since 2000, the fraction of US population with at least a college degree has risen from 25% to 33% (and graduate degrees from 13 to 18%). The average age of college attendance is also rising. In other words, the part of our lives deemed necessary for meaningful contributions to society keeps increasing. One solution (which is already taking place) would be increasing specialization, in other words allowing ourselves to be ignorant in many areas. But if we don’t want this taken to extremes, either our lifespan or rate of learning must be increased in pace with the amount of information worth knowing.

On the other hand, I sometimes hear the objection that with endless time we would end up trying everything and grow bored. This does not seem relevant, for the simple reason that the human race is creating faster than any individual’s capacity to consume6More than a million books per year are published in the US alone, so to even stand a chance of running out you’d have to read three thousand books per day, under the incorrect assumption that the output won’t continue to increase. Similarly, there is no real end to creative processes, nor to improving your ability in whatever area. Certainly you could grow bored of it, but not because you “finished”. A more plausible objection is that without new blood there would be a dearth of innovation and creativity. This does seem to be a general trend, although it is not without exceptions; I think Tempest is an excellent album, and Dylan was 71 when he put that out. Plenty of examples exist in other fields as well. I don’t really have any hard data on this topic, and would not venture to explain what drives creativity in people at any age. But I wonder to what extent a drying up of ideas could arise from a choice not to get into new things “this late in life”…

At this point we’ve covered a lot of possible consequences, so let me conclude with a few short answers to objections that I hear with some regularity:

Curing aging is unnatural: Only if you don’t consider humans and the things we make to be part of nature. Either way, the same argument is equally applicable to correcting poor vision or brushing your teeth. Or to wearing clothes, for that matter.

With endless horizons, we would not be motivated to do anything: Possible, I suppose. But as far as I can tell, a decades-off demise doesn’t really seem to guide our daily routines. Overwhelmingly, our actions seem to be motivated by “I want people to admire me“, “All my friends are going to college“, “This person is nice/mean to me“, “I want that person to get naked with me“, “That guy makes more money than me” … Americans work an average of 47 hours/week, even though less than a third of this would provide food and shelter. We compare ourselves to our peers, and compete for whatever is scarce. When material needs are fulfilled we eagerly compete for scarce intangibles, such as love or fame. And the absence of death would not change this.

Curing aging goes against God’s plan: I am still unable to understand how anything we humans do could legitimately challenge an omnipotent God. If (some) God exists and this goes against his plan, then our attempts will simply fail. No need to worry.

“Death does not concern us, because as long as we exist, death is not here. And when it does come, we no longer exist”: OK, this argument from Epicurus was not actually delivered to me in person. The idea persists, though, and it may even be well-founded. But accepting it does not imply that we shouldn’t seek to make each of our future moments of existence as desirable as possible (which Epicurus would no doubt have agreed with). Whether or not we consider death to be part of our life, curing aging would make the experience better.

To summarize this section, most of our worries arise from imagining a future without aging but absent any other changes from the societal structure we have now. There is no question that things would change drastically if we cured aging. But this cannot be used as an objection, because society is certain to undergo drastic change regardless. Moreover, drastic societal changes were also incurred by codes of law, the steam engine, computers, the internet… Yet now that the damage is done, few of us would want to return to the society that preceded these changes. In some cases we can fairly imagine that change would have been resisted if the full consequences had been known in advance (e.g. pollution post industrial revolution), but nobody is suggesting that we reverse even these examples. 

If you happened to be born female a few hundred years ago, your lot in life was to be pretty, perhaps play an instrument, and hope that whoever you were married off to wasn’t abusive. From our present perspective, this lack of choice seems utterly barbaric. Now imagine that you are restrospecting from a future society that has cured aging: would our lack of choice regarding sickness and death be considered similarly barbaric?

[1] Age outshines even diet (saturated fats etc.) for heart disease, although for diabetes it is second to diet in importance. For lung cancer smoking is a bigger risk (with aging 2nd), but aging is #1 for cancer as a whole. For the various neurodegenerative disorders and dementia there’s absolutely no comparison. And of course there are a miscellany of non-lethal diseases where aging is also the biggest risk factor (e.g. arthritis).

[2] In terms of society, on average about 20% of lifetime medical costs (including birth-related) occur before age 40, ~30% between 40 and 60, and half after age 60.

[3] The effect size is generally larger in simpler organisms. In a somewhat relatable organism, mice, genetic manipulation (of growth hormone pathways) has doubled the healthy lifespan, drugs extended healthy life by ~10% (Rapamycin, Metformin) and caloric restriction 30-40% (although there’s controversy about whether this effect is specific for inbred strains of lab mice).

[4] Not a single “anti-aging” cosmetic sold by under well-known brands has any effect whatsoever on aging. Some may remove wrinkles, but that’s like saying that morphine cures cancer because the pain disappears. Some existing drugs (e.g. rapamycin, possibly NSAIDs) may affect the aging process, although they are not sold for this purpose. A huge number of supplements claim to affect aging, and the vast majority are undoubtedly bogus. A few are based on legitimate scientific studies, though without human studies it’s not clear that they will work as advertised (nor what the relevant dose is). I should note that aging is currently not recognized as a disease by the FDA, which means that one could not get a drug targeting aging itself approved for sale. It is possible that the first effective drugs against aging will be sold as supplements until the regulation changes (though it might change rather quickly if we have something in hand that clearly works).

[5] One successful example of this kind of impetus is the Apollo program, where a large influx of funding and manpower in the 1960s allowed the US to leapfrog the USSR space program.

[6] This ever-evolving world also discredits the concern that a post-aging human race would stagnate due to a lack of natural evolution. I will go over the details in a separate post, but in short the fact that the modern world now changes much faster than our reproductive cycle means that the mechanism of Darwinian selection is approaching irrelevance: increasing the successful reproduction of individuals whose genetics are better suited to the environment will not improve the next generation when the environment that the child grows into is very different from the one that favored its parents.

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