To Beat Death and Become Immortals, We First Must Defeat Entropy

Immortality is the rare superpower that sounds like a curse. And yet, there’s something very alluring about the possibility of never dying. Something must be hardwired in us to avoid death in any context, regardless of how irrational a decision it might be for ourselves or for the species at large.

This, really, has always been the Holy Grail of the biological sciences. Investigating and treating diseases has always had the goal of extending and improving life. The latest technology has contributed to renewed interest in the idea that immortality may actually be attainable. Some researchers would like to treat aging as any other disease (or collection of diseases), as was recently highlighted on Ron Howard’s new show Breakthrough.

These researchers hope to advance the idea that a drug can be investigated for the purpose of treating age itself. Although the drugs they’re looking at have already been on the market for years to treat maladies such as diabetes, the hope is to change the thinking and to investigate drugs for treating age in the first place. What better prevention treatment could there be, after all, than perpetual youth?

Because it isn’t possible to get a drug that treats aging cleared by the FDA, researchers argue, no one in private industry has tried seriously to tackle an aging cure. But once the FDA comes around, so the thinking goes, the floodgates will be open, and the free market will keep us all feeling 24 and virile for centuries to come.

This is an inspiring thought. Before we get too worked up, though, let’s dive into what it means to age.

Life is fundamentally an unstable process (yes, process). Life seems to prefer higher, more unstable energy states to the lowest energy state, which is what makes it so intriguing. Everything in the universe seems to tend towards higher entropy, or disorder. Indeed, the scientist Nicolas Carnot contrived of a principle to describe that tendency that ultimately became a “law”. So when something appears to do the opposite, it feels strange and somehow intentional by something or someone.

It’s worth noting, however, that gravity is also a law. With enough energy, it, like the Second Law of Thermodynamics, can be temporarily resisted (note that the laws are still very much in effect, but are being overcome with work; no physical laws are being violated). The obvious example is a human-made rocket ship, but examples also exist in nature. The surface tension in water, for example, is capable of overcoming gravity. (I should note that it is thought that all of this is possible because we are an “open system,” so there is something to offset our reduction in entropy. Specifically, the Sun is dissipating its way out to equilibrium. We’re using some of the energy generated by the Sun in this process, but the overall tendency in the system is still towards increased entropy.)

So, more plainly, while everything in the universe tends toward equilibrium, equilibrium means death. Equilibrium means an even distribution of all of the constituent elements into the highest state of entropy — total disorder, but total stability. Life does the opposite. It hoards certain molecules inside cells and regulates them. Life instead tends toward an energy-balanced version of stability: homeostasis. In so doing, it has to stand athwart the natural direction of the rest of the universe.

So life is, essentially, the resistance of the lowest energy state, the state of maximum entropy that everything in the system wants to move towards. Resistance to this natural tendency makes the system inherently unstable, and is made possible with just the right amount of energy. Too much energy and everything becomes too unstable and simply melts (or vaporizes). Too little energy and everything simply remains in the lowest energy state. There’s a small window, though, where entropy can be reduced, and complexity can be spontaneously generated.

(An aside: This second law is thought to be irreversible; an egg cannot unbreak, to cite a classic example. But note that there’s a difference between a reduction in entropy and the arrow of time. It’s true — the egg cannot unbreak, but that’s because we can’t go back in time. An egg can indeed be reformed, though, if the components of the egg are recycled through the function of life, as if the components are composted into mulch for a corn plant that in turn feeds a chicken. The circle of life is so-called for a reason.)

While nature tends toward equilibrium, life resists equilibrium and tends toward homeostasis. But again, all of this requires energy. We use energy to resist equilibrium, just as a rocket uses energy to resist gravity. But energy use is costly, and causes wear and tear on the components in the system. Eventually, the pumps and membranes don’t work as well as they once did. Life is necessarily a destructive process!

This destructive process is likely what aging really is. So if we hope to tackle aging, we have to first ask the question: Is it even possible? The components of our system want to tend towards the lowest energy state, just as the components of a rocket want to tend towards the surface of the Earth. In order to resist that, both require energy use, but energy use wears down those very components. If we want to stay alive, we have to use the components in our system, which means we must age.

Still, it isn’t clear why it shouldn’t be possible to circumnavigate this by somehow replacing the components. Shouldn’t we be able to simply replace cells that wear out and thus become unstable? Or is there something inherently unstable about the group of cells, also? After all, cells are thought to replace all of their constituent molecules over time, so why do they die? It’s an open question, but one look at the immortal jellyfish suggests that it should indeed be possible to simply replace everything.

One of my fellow researchers by the name of Jack Davis once proposed an interesting thought to me about this: Maybe aging is an evolutionary adaptation. Because evolution works only when there’s continual turnover of biological material, the turnover itself must have come from somewhere, thus making evolution more efficient. This turnover is necessary to generate new traits and build upon those already developed, a.k.a. evolution. Put more simply, if no one’s dying, then no one’s having any babies, and babies are needed to drive evolution.

It seems more likely to me that aging is a naturally occurring phenomenon that need not be adapted. But Jack’s reasoning may be why aging persists. There may indeed be ways for nature to get around aging, but aging is strongly favored. Evolution gets a strong benefit out of constantly generating new biomass, but it doesn’t get any benefit out of keeping organisms alive after they’ve contributed to the next generation (in fact, they just continue to take resources if they stick around), so there’s a selective pressure to keep aging. And animals that die off probably have incentive to procreate. All of this may explain why we don’t see more examples in nature of immortal animals.

For individuals with conscious awareness who are caught in this system, though, that’s not very comforting. Human evolution may benefit when we all expire at 80, but dying of old age still holds limited appeal.

So here we are again. How might we go about combating age? One possibility is to find something besides oxygen to breathe. Oxygen is a fairly reactive element. In fact, it’s responsible for a tremendous amount of damage to both organic and inorganic structures through the process of oxidation. If we were able to find something a little less reactive, it might be less damaging to our bodies, and we wouldn’t have to invest so much energy in antioxidants to fight these effects.

The flip side of this is that it’s oxygen’s reactivity that makes it so great at what it does. Anything less reactive would tremendously slow the electron transport chain - meaning we would not be able to sustain the levels of activity we need to survive. So maybe we all just walk around in sweet hyperbaric chambers that shield us from atmospheric oxygen and only deliver a little bit to our lungs.

Another possibility is to more generally slow our energy use, since it’s this process that produces the wear and tear on cells. Many of us in the West eat far more than we need to, anyway, right? Though controversial, calorie restriction does indeed seem to be able to prolong life, according to research.

While a disciplined approach like this may yield many benefits (even beyond slower aging), it’s still a temporary solution that merely puts off death. Living a longer life only feels worthwhile if it’s enjoyable. And besides, it’s more fun to think of other possibilities. So why not try to hack the jellyfish?

Though not impossible, this approach has major hurdles. The jellyfish is thought to achieve immortality through “transdifferentiation,” or turning its cells back into stem cells and starting over so they become other cell types. Although we have technically figured out how to turn human cells back into stem cells, humans have many cells that are sort of irreplaceable. Our neurons, for example, let us do what we do by finding the appropriate contacts with other neurons and forming a complex web. In theory, if those cells are forced back into a stem cell state, all of these contacts would be broken, since stem cells aren’t capable of forming neuronal connections. We would theoretically revert back to infancy and know essentially nothing, which seems to be roughly what a jellyfish knows. To live as long as a jellyfish, we may also have to live as poorly.

Maybe one day we’ll be able to get around this by having some sort of continual process that rolls through the brain, takes note of every contact a cell has, transdifferentiates that cell, then lets the newly generated cell grow around it like a scaffold in order to reestablish all of its prior connections, thereby preserving each of its contacts. Memories that involve that cell would therefore only be offline temporarily.

For now, our approaches will have to require targeting genes or drugs that make more efficient use of our energy, or re-fabricating our bodies out of more durable components. Best we can do till then is resist the randomness that the universe has fated for us all.