The “Not Happening in my Lifetime” argument
For much of human history, living up to a ripe old age was seen as a gift from the gods, an aberration, or just the product of sheer luck. Given that up to the beginning of the twentieth century, many of us succumbed to disease at an early age, being extremely fortunate to live past the age of forty, it should be no surprise that living a long life is still considered today as something akin to winning the lottery.
Even when confronted with the galloping pace of scientific advances in human longevity, our historical sensibilities have led us to take a defeatist stance towards the subject: “Even if longevity interventions become available during my lifetime, I am already too late to take advantage of them, so why bother?”
Dismissing the science as being science fiction
Indeed, this hesitation to see human life extension as a real possibility in our lifetime, dismissing it as a dream belonging to the realms of science fiction and futuristic utopias is not an uncommon one, and as long as tangible rejuvenation therapies do not become available, this attitude will be validated as pragmatic.
Today, however, rejuvenation biotechnology is far from a fictional dream; it is a quickly growing field, and advances that may increase the lifespan of you and your children to well over a hundred years are already making their way to the clinic, and this is something we can no longer ignore.
Every reality begins with a dream. Only 114 years ago, the Wright brothers made the first powered flight a reality, and since then, we have taken to the skies, orbited the earth, and landed a man on the moon. What had been an impossible dream for millennia, that of human flight, has, in the span of a century, become a reality of everyday life for all of us. Today, most of us will have flown in an airplane and have ceased to see this as exceptional. It would be short-sighted to think that the same will not happen with new technologies, such as cryonics and rejuvenation.
Rising life expectancy and the arrival of rejuvenation therapies
One of the most powerful arguments for the reality of longer lifespans comes from the astounding increases in life expectancy in the last hundred years. Since the 1900’s, life expectancy has risen from about 47 years in developed countries to 79 years at birth.
Most children born in the West today are expected to live well over their 80’s, almost twice as long as they were 100 years ago, adding up to about 3 months per year! This means that for every four years we can remain healthy, we are awarded another year of life, and with the increasing pace of technologies whose aim is to mitigate, even reverse, the damages caused by aging, this gap is only getting shorter.
This, together with the introduction of genuine anti-aging therapies in clinics and an increase in the number of upcoming clinical trials for these drugs, makes a strong case for the arrival of these therapies in the near future.
In the last few years, there has been a huge surge of interest and investment in senolytics (drugs with the aim of clearing senescent cells), with companies such as Unity Biotechnology, Cleara, Oisin, Senolytic Therapeautics, and many others developing senolytics. Unity Biotechnology is currently developing UBX1325, a Bcl-xL inhibitor that targets a different pro-survival pathway that senescent cells use to evade destruction. UBX1325 is in Phase 1 trials to treat diabetic macular edema, and results are anticipated sometime during 2021.
Samumed is a biotech company developing drugs that target the Wnt signalling pathway. This pathway plays a central role in stem cell renewal and tissue regeneration. In May, 2019 Samumed launched a Phase 3 clinical program of its candidate drug lorecivivint (SM04690) for the treatment of knee osteoarthritis. The results from this Phase 3 clinical trial are expected to land in the later part of this year. If successful, lorecivivint could find broad application for treating multiple age-related conditions through the Wnt pathway.
There has also been a lot of excitement over the work of Drs. Irina and Michael Conboy who have spent over a decade exploring factors in young and old blood which spur or prevent regeneration respectively. They have conducted a number of animal studies suggesting that there are a handful of factors in aged blood which prevent tissue regeneration in older individuals and most importantly, when these factors are blocked or removed, tissue regeneration resumes as it did during youth. This suggests it may be possible to “reset” the signature of aged blood and restore it to a more youthful state. The technology to filter pro-aging factors from our blood already exists too, which means this could reach humans fairly soon.
Filtering the blood of the various problematic factors that drive aging and block tissue regeneration could be achieved using a modified version of an already approved technique known as apheresis. This is a medical procedure that involves removing whole blood from a patient and separating the blood into individual components so that one particular component can be removed. The remaining blood components then are reintroduced into the bloodstream of the patient. The Conboys have founded the startup biotech company IMYu to bring next-generation apheresis to the clinic.
Lastly, in December 2020, Gensight announced that its Phase 3 clinical trial was a success, meaning that mitochondrial gene therapy is now a reality in humans. The trial showed that the vision of those suffering from LHON, a mitochondrial condition that leads to loss of vision, could be restored somewhat through this gene therapy. This success opens the door for treating other mitochondrial diseases as well as aging itself as the mitochondria and their decline are one of the reasons we are.
This is only the tip of the iceberg. At this point, it is indeed challenging to continue to pull the wool over our eyes. Not only are these therapies likely to become available in our lifetime, but it seems that many of them will be reaching the market within the next decade.
Questioning our preconceived assumptions about what is possible
However, reflecting on the feasibility and the desirability of bringing aging under comprehensive medical control inevitably demands that we question many of our preconceived assumptions regarding what is possible, what is or isn’t good for us, and what is acceptable. Disputing what one had long thought to be true—or at least learned to accept—is never without effort or discomfort, and this is especially true when we consider that many of us still see aging as an inevitable, perhaps even necessary, fact of life. It should thus come as no surprise that one of the most common responses to the thought of robust rejuvenation is that of neglect; in other words, why should we concern ourselves with something that might come to pass only after we are long gone?
As we have noted above, the first rejuvenation therapies are certainly not centuries off; they are a couple of decades away at worst, and some, such as senolytics and DNA repair therapies, may be entering the clinic within the next ten years. Unlike people a hundred years ago, we have every reason to concern ourselves with the arrival of medical interventions to target aging, as our efforts now could significantly accelerate the pace at which these therapies will march from the laboratory to the clinic.
Our actions today have the possibility, for the first time in history, to bring a profound change to the number of people who may live long enough to benefit from rejuvenation. By acting to speed up the development of the first therapies in the coming years, we ensure that the large majority of people today are granted the opportunity to take advantage of them; conversely, our inaction will lead to a slowing down of the pace of progress, making the impossibility of robust rejuvenation a self-fulfilling prophecy.
In any case, people who label rejuvenation as a futile pursuit that will only benefit future generations should consider the fact that their children and grandchildren themselves form part and parcel of that generation, and at least they may stand a good chance to evade the ravages of time.
Even if we might not live long enough to benefit ourselves, this thought alone should make this enterprise a worthwhile one indeed. What may turn out to be woefully short-sighted, however, is dismissing rejuvenation as a possibility—or worse, opposing it!—on the grounds that we might not benefit from it personally. If we adopted this stance on climate change, for example, we would be quickly reprimanded as egotistical and lacking foresight.
One of the most common refrains about this grave global concern, in fact, is that even though people alive today might not live long enough to experience the worst effects of climate change and would consequently have little to gain from any countermeasures taken against it, preventing this catastrophe from happening should nonetheless be amongst our primary concerns, even if only to ensure the safety of future generations.
Ultimately, the future is not set in stone, and there is no way to know with absolute certainty whether rejuvenation technologies will arrive soon enough for us to take full advantage of them or not. However, good answers come to those who ask good questions, and maybe what we should be asking ourselves is not whether rejuvenation therapies will become available in our lifetime, but whether the possibility that they might is worth staking our bets on, and given the visible rate of progress in this field today, we would say that it absolutely is!
Despite our efforts, robust rejuvenation might still not have arrived by the time we reach old age, and the bitter taste of disappointment could be a difficult one to swallow. This is understandable. However, there’s another unpalatable dish that might be served cold to us as we prepare to meet the reaper: that of regret. If we do nothing today to speed up the pace of rejuvenation research, we risk spending our final days wondering whether we might have saved ourselves, and millions of others, years of unnecessary suffering if only we had decided to take action sooner.
However, even if regret sets in, if we do our part today, we can go peacefully in the knowledge that we’ve helped build a future free of age-related diseases for our children, grandchildren, and the generations to come. Does the belief that this is possible not make the risk of disappointment taste at least a little less bitter?
 Lazarus Long and the Howard families in Methuselah’s Children (1941) by Robert A. Heinlein; Anton York in Conquest of Life, Thrilling Wonder Stories (1937) by Eando.
 Struldbrugs in Jonathan Swift’s Gulliver’s Travels, 1726.