In part 1, I gave an overview of the current anti-aging research with a focus on what I think is the most promising approach. Now I want to turn to the obstacles to our progression toward a post aging world.
Obviously predicting the future is impossible, and I’d be foolish if I thought I had any insights into what’s going to happen. So instead, I will focus on what trends I perceive today and what they might lead to. My main goal is to think about the best strategy to navigate these obstacles.
There are some narratives among longevity enthusiasts that I think are not quite accurate and it’s worth exploring the whatifs. What if things are not happening as we think they are?
The first obstacle is related to the strategy to defeat aging. Funding in the longevity space can be divided in two type of strategies:
The first is finding ways to tinker with the metabolism to slow aging. We now knows of several metabolic pathways that influence aging, like mTOR or AMPK. Playing with this pathways has been shown to influence lifespan in primitive organisms like worms or small rodents. Since these lifespan extension effects seems to scale down as the “natural” lifespan of an organism scale up, there is few theoretical ways that any such interventions could produce any more than a few years of additional life. Furthermore, these pathways can naturally be influenced by interventions like exercise or fasting. That dozens of millions are spent to try and develop a pill that will might give you the benefit of a good diet and exercise is rather telling of the society we live in, and a waste of money as far as rejuvenation is concerned.
The second strategy, the consensus among the more “radical” anti aging crowd, is that aging is a multifaceted process, the Hallmarks of Aging, resulting from the normal “wear and tear” of metabolism or from some sort of programming, depending on who you ask; To cure aging, we’d need to target each hallmark. This is a strategy that has been championed for years by Aubrey De Grey. And that is a very good strategy. It makes no assumption about what causes aging, it simply target all the changes happening to the aging body to push the body back to a younger state. According to this strategy, it doesn’t matter whether for example beta-amyloids are the cause of Alzheimer disease or not, we need to get read of them because young people don’t have such high levels.
Not only is this strategy very sound, but Aubrey De Grey has made more than anyone to bring public awareness to the cause of longevity. It may be his peculiar long beard or his powerful charisma, but we would probably not be so far ahead today would it have not be for him.
While it is a very good strategy strategy, it might not be the most effective one, as we reviewed in part 1. As much as it is a good thing to diversify the development of anti-aging therapies, the weight of evidence should move us to put more funding and energy on those targets that seems upstream of most hallmarks of aging. Nonetheless, there so far seems to be enough funding for a few approaches to epigenome reset, enough so that we can reasonably expect some of them to reach the clinic in the medium term.
A second narrative widely shared is that public opinion, at some point in the future, will be vastly suddenly swayed to the cause of life extension after which everyone will get to work to democratize anti-aging cures so that we can all live happily forever and after. All it would take, it is thought, is a convincing enough study. Whether it is robust mouse rejuvenation or an impressive human study, one of them will be a catalyst for profound change.
Resistance to change is great
It might be so. Public opinion is unpredictable, and it seems like internet has made it quite volatile, and as irrational as it has ever been. Information overload means it’s likely gonna get harder and harder to get public attention. And conformity bias ensures social homeostasis toward the status quo.
But there are more compelling reasons to doubt this narrative: There are already some really good studies showing rejuvenation in mice. The 2016 landmark study showed a 20 to 30% life extension in mice following the destruction of senescent cells. Another 2016 paper showed that partial reset of the epigenome turn back the clock of aging. But that is not all. We now have a study that showed actual rejuvenation in humans! Each of these studies generated some buzz (mostly online). But each time, the buzz died down and the public at large is none the wiser. The ranks of the longevity community grow a little, bringing in more scientists, more physicians, more enthusiastic people, more money. That is bad at all. But it still marginal. Aging research is as ignored by the mainstream as it ever was.
And yes, we could argue that none of these studies were enough. Not enough sample size. No controls. Just a mice. Or maybe it just misses the key ingredient that might catch public imagination. But here I will argue that none of that matter. No study will ever convince the public because the public doesn’t listen. And if the public doesn’t listen, neither do the politicians. And the money will continue to be hard to come. We have had outrageous headlines claiming the fountain of youth has been found for years now. If a good study is enough to catch the public attention, it would already have happened.
The only way we might possibly get the public attention is if a therapy is officially approved by an authority like the FDA against aging. But that would suppose that authorities recognize aging as a medical target, which is not the case and can not be the case as long as the public consider aging to be in the order of things….
Ok, but there are already numerous potential therapies in clinical trials right? Surely when they are approved things will change? Let’s examine how things might change. We will talk about the FDA mainly as it is the locomotive of the regulatory system of healthcare development.
In our current market-based system, the development of therapies to the clinic is carried out by the private sector, with varying level of involvement of governments around the world. The only incentive of private company is to be profitable. Patent laws have been designed to increase the possibility for a company to make money out of a product whose development cost dozens or hundreds or even billions of dollars, most of this cost coming from the regulations they have to follow. Discussing this system is far outside the scope of this article; I just layed out the foundation for what comes next.
So the only choice for a company willing to get its therapy approved on the market is to target officially a specific disease. Fortunately, aging is the root cause of a plethora of ailments like sarcopenia, dementia, cardiovascular diseases,… Plenty to choose from. But already, the incentives start to diverge from the goal of a comprehensive cure for aging. Take Alkahest for example: instead of developing a single therapy targeting the aging process as a whole, which we hypothesized to be possible in part 1, they are trying to bring multiply therapies to match the numerous individual diseases of aging. At the end of the process, we will have numerous therapies that individually will not do much against aging. It takes mission oriented individuals to focus on the bigger picture and fight against the pressure to maximize revenues. And considering how arduous is the process of getting FDA approval, let’s just say that the odds are not good.
Fast forward a few years. You have a bunch of therapies officially approved on the market. Each for a specific disease. The longevity community is ecstatic. Longevity escape velocity is here! Is it, though? By law the companies behind will not be able to advertise the anti-aging effect. And if you go to your doctor and ask him to prescribe one of this therapy, you will likely have a blank stare and a polite goodbye. Ever tried to get metformin, one of the safest and most used drug that has a positive impact on longevity? Why would it be different with a newly approved therapy? And even if you find the right doctor, you’ll have to pay for each of those therapy the price that has been designed to extract maximum value from health insurances. In short, these interventions will be available for the few that are rich and connected enough. The public at large will ignore life extension as still a pipe dream.
If you think I am being pessimistic, consider our current situation: We could already quickly and cheaply add at least a decade to the current healthspan in developed countries! A third of americans are obese, another third are overweight (link), a third of americans have prediabetes, and so on and so on. All of these can be classified as metabolic syndrome, and though age is a factor, by far the biggest factor is lifestyle. It is costing billions of dollars in healthcare every year, and millions of healthy years of life lost. And it is completely reversible. And yet, its prevalence is still on the rise worldwide. The causes are multiples, and if you are interested in reading more about it, Food Fix by Mark Hyman is a very good place to start. But whatever the reasons, here we have interventions that are available today, are free, would add years of healthspan, save trillions of dollars to society, and yet is not implemented.
Similar is the case with the few interventions like Metformin, as we mentioned earlier, which are cheap, safe, widely available, have been shown to increase lifespan and yet are never prescribed for this purpose outside a small circle of connected people. Why would anything change just because more interventions become available?
Hostility is worse than apathy
The lack of public enthusiasm for healthy longevity can be disheartening. If only we had a few hundreds of millions of dollars, we’d be immortal already. Or so the thinking goes. So a lot of effort in our community goes toward advocacy. And that is the right thing to do. We want to touch every people on earth, because every life is sacred and everyone deserved to be spared the sufferings of aging.
Still, there is a scenario worse than apathy: hostility. As said above, public opinion is a volatile and sometimes irrational beast. It can be hard to predict where it will lend on a subject. Nuclear energy is virtually carbon free, cheap, abondant, the radioactive waste are objectively a trivial issue to manage (because there is so little of it), so it should be the darling of an eco-conscious society, especially because the lack of storage option makes it the only scalable clean energy so far. And yet it is quite tabou especially in environmental movements, for some reasons. That’s an example among others that mainstream opinions not always coincide with reason.
Who knows how the public will react. The development of the first therapies that have a real impact on aging will influence this reaction, among other factors. The most advanced therapies are senolytics. If for example those drugs have a short term benefit, but end up decreasing maximum lifespan in the medium term, as some fear, the backlash could be severe. I don’t think this hypothesis is likely though. The data we have on the few self-experimenters that share their experiences hints to a beneficial effects that last for years. And even if the aging process does end up been accelerated eventually, it is unlikely the link can be definitely proven in the public mind.
Another reason would be that the first therapies becoming widely publicized will be expensive enough to anger people, and misguided anger can end up thwarting further development in the name of equality rather than letting the rich fund the development of cheaper therapies, as happen for lots of technologies.
There can be many reasons why the public will start to become hostile to the research against aging. And if that happens, that will make progress will crawl to a stop.
The good news is that, as I speculated in part 1, the research against aging is already very advanced. We shouldn’t need much more fundamental research now. It might not take long to have a true anti-aging therapy available to the public. If it is affordable enough, that could be enough to win the public heart. Because it is one thing to prevent research against an hypothetical cure, it is another thing to prevent billions of people from trying to stay young if the means to do so exist already. If just one clinic open in a third world country somewhere, the tide of clients will be too hard to stop.
This is where I want to end this part 2, on an optimistic note. I think the best chance for universal anti-aging therapies is to present the public with a “fait accompli”, a therapy already available, affordable enough for the majority of people to benefit from it right away.
In part 3, I’ll conclude with what I think the best strategies are for the “average person” like you or me to make a post-aging society a reality as soon as possible.