On the challenge of age and time reversal

I fib when I say that my PhD in physics is completely unrelated to aging. It’s partly about reversibility or, rather, irreversibility of time. Ironically, one of my aging papers has “challenge of age reversal” in its title, scaled down from “impossibility of age reversal” as per a reviewer’s request. Age or time, there’s no way we’ll reverse it.

I’m also guilty of filching a few quotes about breaking physical symmetries from Vladimir Nabokov’s “Look at the Harlequins!” for my thesis’s epigraphs. If you’re ignorant of Vad’s struggles to spatially rotate his vivid night dreams, I may recommend reading it. I similarly have been struggling with the possibility of reversing time both in physics and biology.

Everyone knows that time is irreversible, there’s no time machine. The very fact of irreversibility makes life worth living, does it? Even in very simple physical systems as soon as you have 3, 4 or more things interacting, mathematical reversibility of equations turns into physical chaos. Any slight deviation would lead to exponential divergence. By going back, we only end up in a different state. You can only have an illusion of reversibility for an instant which quickly fades away.

Life has found a fundamentally different approach: instead of trying to reverse time, it tries to remember and record its history — “ontogeny recapitulates phylogeny”. Life recalls every single state it was in and memorizes it, basically encoding it into your species’ DNA. Follow the playbook of your ancestors to survive.

Of course you can deviate from the original state, but the way that approach works is that with every new generation you remember and memorize more and more about how life can exist on this planet. Each organism is well trained, well prepared from the very beginning by their ancestors to survive. Rules are written in blood, so does the DNA.

There aren’t any real examples of life solving its irreversibility. Life is stuck in an infinite cycle where it just gets better and better with every iteration. Every new generation is selected to be a bit better than the previous one — to live longer, to be more adapted to the environment.

The premise of aging research is to try to reverse the flow of life, or at least slow it down. I haven’t really found any ways to reverse it, to be honest, I don’t believe it’s possible both due to physics and biology constraints. We will need alien technologies to do so. By alien, I mean something that we’re hundreds if not thousands of years away from.

On the other hand, the easiest way to solve aging is to follow nature’s path. We could edit embryos, edit the germline, and use everything we know about aging to prevent the next generation of kids from ever struggling from aging. Maybe they will live 3 to 10 times longer, yet, they will develop some novel aging phenotypes which we are unable to contemplate now. Then, we’ll have to edit them again and again. That’s basically what evolution has been doing so far with no rush.

Of course we can speed evolution up, and most likely we will. But there’s irony in the fact that we just cannot do it to ourselves.

Why? Because we start as a single cell. When our parents’ gametes combine and reshuffle their DNA, they launch the development program and one cannot unroll it. Nobody can. Every single cell within the body has its own program, they talk to each other and they form tissues, organs, your body — and they know how to survive and keep that thing (you) together for 20 to 25 years in a decent state of health.

Then, the playbook of life is over and they just don’t know what to do next. They have some redundant capacity to go on for almost three times longer, up to 100 years, but the guarantee period is already over. That’s aging.

Life has memorized how to develop you up to 25 years — not everyone, of course, but the luckiest ones who are healthy will develop without any major health issues. That’s the apex of 4 billion years of evolution. They would be able to regenerate the tips of their fingers for 14 years.

Then, they will mature into a healthy adult and start procreating, thus giving birth to the next cycle of life, and rendering the remaining body a soma, or, basically, evolutionary waste. The biological organism (you) — every single cell of yours starts slowly losing function, accumulating errors, making mistakes, accruing damage, whatever you call it. At some point, all fancy damage repair mechanisms fail one by one.

You can replace cells, you have stem cells which can do that. But there’s always a limit to how much those repair mechanisms can fix. You need to fix the repair mechanism itself too. So you need repair mechanisms for repair mechanisms for repair mechanisms for… you understand the point. It cannot go on forever.

So far evolution has been trying to add more and more layers on top of each other. Having a tissue instead of a single cell was a huge advancement because you can simply replace cells now. But when you think about the age of the whole tissue, you can’t replace all of it. You start replacing every single cell, but the necessary connections between them are lost. The cells cross-talked for years and arranged in a very specific way — a good example is your brain. You can start replacing neurons one by one but they build long range connections — axons and dendrites — to thousands of their neighbors. How would you rebuild all of them? Sometimes that’s just impossible.

There’s this concept of emergence in physics, when you combine a few simple things together, and they form a new emergent layer of self-organization. Many are qualitatively different from one. A sand dune behaves differently than a single grain of sand. New emergent properties develop that are just absent from the simple components of the system.

The annoying thing is that our DNA is limited; we only have about 3 billion base pairs, and you can only record so much in it. The density of information compression is insane because a whole body is built according to this script. That is the result of 4 billion years of evolution — writing and rewriting the DNA code, selecting the best variants, mixing them together, improving them, randomly breaking them, and hoping it wouldn’t make things worse.

It didn’t evolve to reverse time and age — hence we cannot copy it from natural evolution. We’ll have to figure out the solution to aging from scratch ourselves.

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