The Age Old Question

Written by Morgan Beale

Do you want to live forever?

It’s not a new question. Both history and fiction are replete with stories of people searching for ways to stretch beyond their three-score and ten allotment, usually with an unpleasant twist at the end. Take the Chinese Emperor Qin Shi Huang, who issued an imperial decree that his doctors find him a way to live longer, then promptly dropped dead at 49 from the mercury in one of his ‘immortality’ concoctions.

What is new, as David Sinclair and Matthew LaPlante convincingly recount in Lifespan, is the idea that the quest for longer, if not eternal, life, might actually be a fruitful one.

So what has changed, to make the oldest impossible in the book seem like it could be possible after all?

As so often happens, it seems that until now the solution has evaded us because we have been asking the wrong question. As Sinclair and LaPlante are at pains to point out, medics have spent centuries looking for the immediate answers to the most pressing query of them all, ‘why do we die?’ And no-one is questioning that their answers have held us in good stead. The revolutions in health care that now prevent millions dying from diseases such as smallpox and cholera have been gratefully received, and played no small part in dramatically increasing the average lifespan. However, while this focus on isolating and treating a single specific answer to the mortal question is even now slowly increasing our average lifespans, Sinclair and LaPlante note that all of these new treatments for heart disease, cancer, diabetes and the like have not at all shifted the maximum lifespan.

Why? Because even though a new cure for heart disease might get you through an extra year or two, you’re just as likely to succumb to a stroke, or a cancer, or… well, any of the many medical disasters that come with old age. And that, of course, is the real problem; the accumulated damage to our system that we think of collectively as aging. When a body simply can’t regenerate itself any more, it isn’t enough to keep adding band-aids on the next part to break.

This, then, is the solution that Sinclair and LaPlante have devoted their careers to researching. We die, barring accident or infection, not because our heart might give out or our brains atrophy; we die because we age, and the aging is what causes the more obvious form of death. It is often said that a well-formulated question contains the seeds of its own solution. Now, we can ask ‘why do we age?’ And, more provocatively, ‘do we really have to age?’

In Lifespan, the authors assert that the answer to the former question is in our grasp, and the answer to the latter is tantalisingly optimistic.

The trick, it transpires, is a bit of biochemical sleight of hand. We’ve evolved to live fast and die young when times are good, making the most of times of plenty by reproducing as much as we are able. Since, however, procreating is much less likely to pay off when times are poor, we’ve evolved a kind of biological switch to a kind of conservation mode, where we husband our scarce resources and focus on repairing damage rather than creating new mini-mes to feed and care for.

Amazingly, the enzymes responsible for managing this circuit in yeast appear to be conserved in mammals, like ourselves or the laboratory mice that have been doing a lot of the heavy lifting in Sinclair’s work. Dubbed sirtuins, these enzymes repair our fragile cells by regulating gene expression, cleaving acetyl tags from histones to expose repair related sequence of DNA, and hiding genes that the body on switches on when times are good. While one sirtuin is enough for yeast, humans and mice have seven sirtuins, each adapted for a slightly different specialisation. Their influence helps us mute inflammation, combat muscle wastage, osteoporosis, arthritis, boost memory and endurance, and more. Their attenuation as we grow older appears to be a leading cause of what we think of as aging.

However, by tricking the body into thinking we are living in precarious times, we can induce more sirtuin activity, coaxing our cells to repair damage that we might have pushed through in good times. How? The most well established methods involve under-eating and fasting, particularly avoiding meat, exposing oneself frequently to temperatures hotter or colder than are comfortable, and stressing the body directly through rigorous exercise. Oh, and it goes without saying that one should avoid the obvious toxins while doing so. No cigarettes, and no alcohol either if you want to do it properly. All this recalls the old joke:

Harry walks into his annual checkup, and proudly says to his doctor, “Doc, I do all of the healthy things. I don’t smoke, don’t drink, I don’t eat meat, I don’t even gamble. I skip a meal a day, keep myself on the edge of a chill most of the time, and run hard every day. How long do you think I’ll live for?”

To this, the doctor shook his head and replied, “Why do you care?”

All of these established methods directly evoke the survival circuits, making the body think that it is under stress by actually putting the body under stress. Of course, that might be the prescription for now. But since we know now quite a lot about the pathway regulating this switch between repair mode and fornication mode, thanks to Sinclair and other scientists in his field, we may not need to go to such lengths. Instead, direct activators of the sirtuins, such as nicotinamide mono nuclide, or even genetic therapies increasing expression of sirtuins or the number of situin gene copies available may soon provide an easily achievable lifespan extender.

With the knowledge and technologies we have now, it isn’t a stretch to imagine that drugs to induce sirtuin activity will be on the market soon. Once we can all start to enjoy longer, healthier lives with just a simple, regular pill, the world will change forever.

Exactly how it changes will probably depend on where, and by whom, the most effective solutions are invented. Let’s call the eventual immortality solution Methuselin. How much would you be willing to pay for a daily dose of Methuselin that could add twenty healthy years to your life? How much for fifty years? Or a thousand? And how much would a big pharmaceutical company think it could charge you for the privilege? If Methuselin were invented in a capitalist paradise, it could well be that only the super-rich can afford to live forever, while naturally inducting the inventors themselves to that lofty status. Ironically, inventing Methuselin, with its promise to help you live longer, might find you murdered so that someone more powerful can collect on what must be nearly unlimited profits.

In this world, inequality is exacerbated to a degree never previously thought possible. With lifespans many times the length of us peons, the richest élite can continue to increase their capital holdings and their power over centuries, without even the leveller of aged death to redistribute some meagre portion of their vast estates. In such a world, to be one of the 0.01% (for these people will be few, and will become fewer over time – why squander your fortune on multitudinous offspring when you can achieve immortality in your own right?) will be to live a life of incredulous privilege, while to be one of the remainder will be to eke out a short and brutal existence under the yoke of inescapable Death, waiting in vain for a latter-day Prometheus to steal the gift of life from the gods.

But fortunately, the future is a many-faceted jewel, and this isn’t the only vision we can see in it. Rather than a greedy and self-serving corporation, Methuselin may yet be invented by a kind hearted philanthropist, or someone whose social conscience outstrips her desire for wealth. This generous soul might see the world embark on programs like the golden rice project, where extra vitamins are grown in rice to remedy mineral deficiencies, incorporating Methuselin into daily staples so that it is maximally available, and that everyone can share in the bounty of long life.

In this more optimistic world, there are still challenges to be overcome. Even once the ancient scourges of war and famine are conquered (with so much life at stake, throwing it away on someone else’s cause starts to seem foolish!), overconsumption and resource management loom large. When people stay alive longer, they consume longer, and many argue that the natural world won’t be able to support everyone. After all, it can’t even support our current population. It’s a tough nut to crack, but there’s something the pessimists hadn’t thought of.

It used to be said that a land was in good shape when old people planted trees whose shade they knew they would never live to enjoy. In the era of the market state, horizons narrowed, and those folk kept their seeds to themselves, focusing on the here and now. But when Methuselin unlocked the future for everyone, the horizon started to recede. When anyone can plant a tree and expect to enjoy its fruits themselves, more trees are planted. When the policymakers found themselves planning not just for how to make themselves comfortable for the next few years, but how they might like to live for decades to come, finally, the impetus for sustainable change became irresistible. And while it took time, a lot of time, to slow down and eventually reverse the damage to the natural world, time was a resource that for the first time, we had.

Chances are, the future will lie somewhere in between these two extremes. But who knows? If Sinclair and LaPlante are right, and the cure for aging is nigh, we may yet make our own future.

Lifespan (2019), by David Sinclair and Matthew LaPlante, is published by Thorsons and is available in all good bookstores!