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Comment by rossdavidh | Hacker News Reader

"Ageing seems to affect cellular processes in the same way across five very different kinds of life — humans, fruit flies, rats, mice and worms — according to a study published in Nature on 12 April. The findings could help to explain what drives ageing and offer suggestions for how to reverse it..."

Well, given that ageing seems to affect cellular process across five very different kinds of life, the most obvious conclusion is that defeating the process has some unavoidable, bad tradeoffs. I mean, I'm 55 years old and not looking forward to dying, but let's be realistic here: we're not going to "reverse" ageing. Evolution has had billions of years to do it, and for whatever reason the conclusion is that either it's not possible, or the cost is not worth it. I don't think we are smarter than evolution, in this regard.

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I don't think we are smarter than evolution, in this regard.

Evolution is not smart at all. It trends toward reproductive success and that's all. At the most basic level, natural selection is an emergent phenomena of an energy-scarce environment. That is no longer the case for humans. A single human now has access to orders of magnitude more energy than any of our ancestors. It no longer matters if keeping an individual from aging requires ten times the energy input of creating and raising a child. That entire realm of biological innovation is completely invisible to traditional evolution.

> A single human now has access to orders of magnitude more energy than any of our ancestors.

Now, but it's not clear at all how it will evolve in the fairly near future :-).

But I generally agree with your point on evolution: it is a random process. We tend to "personify" it ("evolution chose to make us like this"), but that's wrong: species that evolved to being less fit died, those that evolved to be more fit survived. Pure chance.

Evolution is not a random process. Natural selection acts on genetic variability in a population; selection is inherently non-random. A component of variability is due to random mutation. Just because evolution does not have a priori goals or fixed directionality does not mean it proceeds randomly.

Right, yeah obviously the selection part is not random ("the fittest survives").

I guess my point is that there is a tendency to say "evolution chose to make this because that's the optimal solution", where actually evolution may have "missed" the optimal solution.

But evolution is not an active process (of something choosing what's optimal), but a passive process (it does change, and some of those (random) changes win).

Or am I missing something?

I don't think you're missing something, although there are many nuances here. Selection certainly converges on local optima, but yes, there's nothing making a "choice" to do so (except with sexually selected traits and mate choice). It's just how it works.

In general it's unsurprising that selection misses hypothetical universal optima for the same reason it's unsurprising we didn't evolve wings even though that'd be an optimal way to escape lions. Evolution moves traits around fitness landscapes heavily contrained by exaptation. But interestingly many highly conserved mechanisms, e.g. essential cell machinery or metabolic pathways shared widely across the tree of life, have been shown to be maintained at absolute energetic and informational optima.

I think Smil had calculated this energy to an equivalent number of laborers working for us 24x7 (like slaves). IIRC it was like 172 or something. It may sound fantastic but once you start imagining what kind of human labor it would take to keep your home heated 24x7, manually achieve what your appliances accomplish (when was last time you had ice delivered or washed your clothes at the river?), your transportation, and have the weather forecast available at any moment, etc., etc., it becomes really clear that 1st worlders live like pharaohs.

I once tried to come up with a reasonable number and ended up with something like 24 slaves per person given a central European living style,

Do you have a link for your number, would be very interested.

I believe it's in "Energy and Civilization: A History", and probably reprised in "How the World Really Works".

This is rando google search for it (so double check) but material looks correct to me:

"An average inhabitant of the Earth nowadays has at their disposal nearly 700 times more useful energy than their ancestors had at the beginning of the 19th century. Moreover, within a lifetime of people born just after the Second World War the rate had more than tripled, from about 10 to 34 GJ/capita between 1950 and 2020. Translating the last rate into more readily imaginable equivalents, it is as if an average Earthling has every year at their personal disposal about 800 kilograms (0.8 tons, or nearly six barrels) of crude oil, or about 1.5 tons of good bituminous coal. And when put in terms of physical labor, it is as if 60 adults would be working non-stop, day and night, for each average person; and for the inhabitants of affluent countries this equivalent of steadily laboring adults would be, depending on the specific country, mostly between 200 and 240."

So looks like my number was quite low.

The references to "Earthlings" makes me suspect this quote was pulled from "How the World Really Works", since it starts out with a thought exercise using an extraplanetary observer watching the progress of human civilization over millennia. If you like this kind of information, I would highly recommend Energy and Civilization, it's a fantastic and eye-opening book.

Edit: confirmed, above quote is from "How the World..".

Awesome, thanks a bunch!

> Evolution has had billions of years to do it, and for whatever reason the conclusion is that either it's not possible, or the cost is not worth it.

To be fair, in the "eyes" of evolution, once you stop breeding, you are effectively dead weight and a resource sink - there's been no benefit to evolving hyper-age solutions. I guess mayflies are the ur-example here - they grow, they breed once, they die and leave all the resources to the new crop.

Even if you kept breeding, as your age goes up, your ability (absent modern medicine and luxuries) to get your children to breeding age goes down (a 20 year old has a much better chance against a sabre-tooth tiger / flu / cold weather / etc. than a 70 year old...)

I’m not so sure this is the case. Older humans have societal roles that free time and resources for younger humans to breed more and work more so the group has more resources. The invention of grandparents was a big thing for our ancestors.

And this is exactly why we don’t drop dead right after we have kids. We are optimized to stay alive and support our our offspring until they have the highest chance of survival and reproduction (and maybe their kids?) so 20+20+10?

Nowadays people don’t have kids until 30, so maybe there is some pressure towards 30+30+10?

There is some thought that social animals that live past their breeding age still play a role in passing on their genes by increasing the fitness of their relations. For example, by helping your sibling's offspring pass on their genes, you are effectively helping pass on roughly 25% of your genes. I don't totally know where I read this but I'm pretty sure it's in selfish gene by Richard Dawkins.

This is pretty rare in nature, however. There are very few species that live past reproductive age, I think humans and cetaceans are the only ones who do it.

"Man had always assumed that he was more intelligent than dolphins because he had achieved so much — the wheel, New York, wars and so on — whilst all the dolphins had ever done was muck about in the water having a good time. But conversely, the dolphins had always believed that they were far more intelligent than man—for precisely the same reasons". — Douglas Adams

Makes a ton of sense, doesn't it. We're attributing our preferences - biological, cultural, etc. - to the good stuff, then later on "discover", piece by piece, that we're not that special. I know many truly intelligent people who do feel humans are special and it's been blowing my mind for decades

Women outlive their reproductive years (and men too!): https://en.wikipedia.org/wiki/Grandmother_hypothesis

Isn't the entire field of medical science just a list of things we've managed to do for the body that evolution failed to manage over the course of billennia?

No, the majority of health issues are personal. Evolution optimizes species not individuals, so while some kids need glasses most kids don’t.

Evolution’s response to massive physical trauma can be things like wariness of heights rather than a body that can fall arbitrarily distances.

It weren't for medical science I'd be dead multiple times over by now due to causes that someone with better genes would have survived.

> Evolution’s response to massive physical trauma can be things like wariness of heights rather than a body that can fall arbitrarily distances.

It can be either or both. Cats tend to survive falls very well, as do insects, but for different reasons.

I don't really get the distinction. I do get your point but x% of a species needing glasses is a species level error. And our entire species was susceptible to things like smallpox before we had vaccines for that stuff.

The threshold where kids “need glasses” isn’t the same threshold where people would be unable to survive in the wild without them.

Also, species level survival is based around fairly large families you see before birth control. Not everyone needs to make it.

That's the point though: we have much better infant mortality rate now, and the kids who grow up don't need to worry about their eyesight etc., ergo we're doing better than evolution alone.

Better by our own yardstick, but evolution can get plenty of people to adulthood without any medical issues.

A frog egg would presumably prefer an evolutionary strategy that involved fewer eggs and a more caring parent. However, the willingness to fail allows for more long term flexibility. Which is presumably why many species place their young in an immediate live or death struggle with their siblings.

To be more accurate, evolution optimizes populations, not species.

Anyway - there are dangers we've evolved resistance to. We have powerful immune systems that fights off tons of diseases. But they fail against some diseases, and medicine helps us there (sometimes). Some of these diseases are extremely widespread and threaten populations.

Am I misunderstanding your comment?

Largely yes, but I would point out that humanities resistance to disease is vastly better than individual resistance to disease.

For example Rabies has close to 100% fatality rate when untreated and has been a threat for vastly longer, but COVID more people over the last 100 years. So what’s a serious threat to an individual doesn’t necessarily mean a major threat to a larger population.

In that context there was likely significant protection offered by our aversion to the ill when we were primitive tribes with limited contact to each other. Such aversion could act as an external immune system causing most excessively deadly to burn out and pushing for ever less deadly strains over time.

Fair points. But do we actually have a biological aversion to illness? That strikes me as cultural (and fairly recent). I understand things like leper colonies to be exceptional, not typical. We've had various theories of disease before scientific ones and they mostly didn't consider contagion.

There’s competing reactions, taking care of sick family/tribe members has obvious benefits and prior exposure is likely. Anyway, it’s hard to say how much of this is cultural, but multiple cross cultural aversions at least have the side effect of reducing contact with disease.

“Pathogen avoidance: Uncanny stimuli may activate a cognitive mechanism that originally evolved to motivate the avoidance of potential sources of pathogens by eliciting a disgust response. "The more human an organism looks, the stronger the aversion to its defects, because (1) defects indicate disease, (2) more human-looking organisms are more closely related to human beings genetically, and (3) the probability of contracting disease-causing bacteria, viruses, and other parasites increases with genetic similarity."[8] The visual anomalies of androids, robots, and other animated human characters cause reactions of alarm and revulsion, similar to corpses and visibly diseased individuals.[9][10]” https://en.wikipedia.org/wiki/Uncanny_valley

People’s near universal aversion to the smell of rotting flesh and human shit are similar examples. Of course at the individual level this is less universal. Another possibility is heightened pain response around minor skin damage compared to larger injuries. Aka thorns and paper cuts hurt so much because that kind of injury was actually more dangerous than moderate blunt force trauma which damages more flesh but doesn’t risk infection.

PS: That said it’s not like we can actually test these theories. It’s mostly an interesting idea that seems plausible.

Evolution is not optimizing for your personal happiness. There are some species that are virtually immortal [0] and even they can reproduce sexually.

It’s just better for you to die. Your DNA sucks, make room for your superiors (your children).

I jest, but dying is the smart choice. It’s like a giant AGI system letting a few of its minor instances being cut off: no problem, we’ll fork a few new ones. They might even be better.

[0] https://en.m.wikipedia.org/wiki/Turritopsis_dohrnii

and with gene therapy, all of this could be resolved

I’m not completely convinced I want it to be solved. While I don’t mind Mr Musk right now, it’s another thing entirely to have him and his friends around for eternity.

Why does it matter as long as you get To live forever?

Oh me too? In that case it’s even worse.

Lol. But to each their own, I’m -currently- middle class (struggling) and I’m very much looking forward to anti-aging.

To struggle longer?

I fail to see many win-win scenarios in a world where population density only increases.

Living longer means you have more opportunities to succeed without being constrained by time (getting old).

But now everyone has that opportunity, so nothing changes, only you get to experience it longer.

Bad stuff also has more opportunity..

> Evolution has had billions of years to do it, and for whatever reason the conclusion is that either it's not possible, or the cost is not worth it.

For a lot of history dying young was common due to forces that have nothing to do with our own biology. So maybe it's more that environmental conditions did not give any reason for evolution to select for longer life, or select against cells that age. Also it might be that there are trade offs about selecting against cells that age that may have been sucky in the past and not led to fast reproduction, but that those trade offs don't matter now.

Cancer is possibly one of those reasons. Cancer cells can reproduce endlessly, so there is good reason to select against cells that do that.

Some animals age very, very little: https://en.wikipedia.org/wiki/Negligible_senescence

Among them the Naked Mole Rat, a mammal.

So it looks like evolution can do it. But it usually doesn't.

In some animals old age has a reproductive advantage. As for turtles and some fishes: Old age => Bigger => less predators + more eggs

For these species most of the new born are babies of very old females.

> Evolution has had billions of years to do it, and for whatever reason the conclusion is that either it's not possible, or the cost is not worth it. I don't think we are smarter than evolution, in this regard.

I think the reason this isn't a pretty solid argument for its infeasibility is that evolution optimizes for different things than we might choose to.

Cost to whom? The genes? Sure. But as an individual, I'm willing to pay that cost (decreased diversity among living individuals; society supporting a non-reproductive member etc).

We are not slaves to biological statistical optimization. Haven't been for what? half a million years.

Preventing aging is in most cases not beneficial from an evolutionary standpoint and it appears some animals, like octopi [0], have evolved self-destruction mechanisms [1] because normal aging mechanisms takes too long to kill them.

[0]: https://www.smithsonianmag.com/smart-news/scientists-figure-...

[1]: https://en.wikipedia.org/wiki/Phenoptosis

I don't think it's about being smarter than evolution or not. We're optimizing for different things. Evolution optimizes for reproductive success. Our society is optimizing for something more like overall well-being. Evolution doesn't care if your life sucks as long as you pass on your genes. We do.

> I don't think we are smarter than evolution, in this regard.

Evolution has two things over us: it has infinite time, and infinite resources. It can afford to wait 200000 years, and to kill millions of individuals, to produce a change.

That's impressive, but it is also the opposite of smart.

There is some evidence that aging evolved following the permian extinction. Animals that evolved prior to the permian extinction such as the Tortoise often do not show traditional signs of aging. It's possible that aging evolved to improve species adaptability.

To be fair, bad genes need a way of being permanently kicked out of the mating pool. Death is perfectly effective at doing so.

> effective

That's what we call a "patch". A systemic patch, in this case.

It doesn’t have to be death by old age though. There’s many other ways for bad genes to get themselves killed.

i'm no expert, but i think dawkins explains this in his 'bottlewrack vs. splurge-weed' sketch

as far as your genes are concerned, it's just as good if two of your children carry them on as if you carry them on yourself; there is no particular reason a priori for evolution to favor one over the other

however, your gametes form a genetic bottleneck which reduces genetic diversity (chimerism) among the cells of your children compared to the genetic diversity among your own cells

due to mutations during your lifespan, genetic diversity within your body increases, which increases the prevalence of genes that cause individual cells and tissues to compete with one another rather than cooperating; in the extreme, we call this 'cancer'

so we have genes like https://en.wikipedia.org/wiki/P53 which both cause aging (by suppressing stem cells, so you can't regenerate) and suppress cancer; more generally, many aging processes are known to suppress cancer directly

but more generally you can see genes' investment of resources in your offspring, rather than in you, as a way to protect that investment from cancer: if you get cancer, it almost never kills your offspring, so your genes can toss your worthless body onto the trash heap and continue on their merry way unmolested

of course you may feel differently about the importance of your own body surviving than (the optimization goals of the natural selection process selecting) your genes do

> due to mutations during your lifespan, genetic diversity within your body increases, which increases the prevalence of genes that cause individual cells and tissues to compete with one another rather than cooperating; in the extreme, we call this 'cancer'

This is a good summary. Only thing to keep in mind is that an increase in genetic diversity need not imply a unidirectional march towards cancer, but an increase in risk. One of the most interesting paradoxes of cancer initiation research currently is the presence of "cancer-causing" mutations in phenotypically normal cells for decades prior to the appearance of the first cancer cell (see https://pubmed.ncbi.nlm.nih.gov/27059373/ for instance).

What's remarkable to me about this aging study and others like it is that they are able to reverse some aspect of aging despite the accumulation of genetic diversity with age as you point out. Perhaps what they're reversing was never really dependent on mutation accumulation with age, or that the presence of mutations does not fully explain the age-related degeneration they're interested in reversing.

Is there much evolutionary pressure for a longer lifespan? As long as you have offspring and live long enough to raise them, there may not be much pressure to increase lifespan.

You're assuming that reduced aging is a huge evolutionary benefit. It seems pretty obvious by looking at difference species that's not true. Look at lifespans across species. The difference in species lifespan is over two orders of magnitude. So evolution has made progress on this.

Evolution only prioritizes lifespan as much as it needs to vs other reproductive goals.

See https://en.wikipedia.org/wiki/Evolution_of_ageing. It seems that there's only slight or negative evolutionary pressure against ageing.

Well there's evidence that goes against your conclusion. Turritopsis dohrnii is a living example of a species which can reverse its age (and as far as we know, can do so indefinitely). It is quite a successful species.

> the most obvious conclusion is that defeating the process has some unavoidable, bad tradeoffs

I think it's related to reproduction - immortality would mean you're competing against your offspring for resources.

Paolo Bacigalupi explored the other side of that coin in his short story Pop Squad (also made into an episode of Love, Death, and Robots). If you live forever, what's the point of having offspring?

It also touches on a theme of The Hydrogen Sonata (and elsewhere in the Culture series): with unlimited time to practice, how far will one go to perfect one's art (music in this case)?

Slowing down aging would also slow down evolutionary selection. As others mentioned, it’s very unclear that evolutionary selection, which optimizes for reproduction, would benefit from longevity besides what humans already have - elders living past reproductive age, helping raise following generations. The actual living humans are much more incentivized to solve the longevity problem.

Why would you need evolutionary selection if we’d be in total control of our species? In theory we’d be able to adapt our bodies as needed, manually.

I get it, for example, in botany where genetic diversity is crucial for the survival of a plant species.

Not total control.

We could engineer away things that might eventually in some future crisis prove to be a deciding factor in our survival. We could easily engineer away genes that might have gone on to outlive us as humans, and then end up outcompeted by them. Or we could engineer ourselves into different variants, and compete with each other.

In the end you can’t second guess evolution.

Senescence is error correction. We have babies and die instead of living forever and budding because 'compressing' an organism down to millions of gametes which are then 'decompressed' by growing new organisms from them is relatively pass/fail. If it works then you get a faithful copy. If it doesn't then the result typically gets recycled.

yes, but there are species not too dissimilar from us who live much longer lives - bowhead whales, for example, can live to 200. and extended lifespan goes along with extended healthspan - so we don't have to live the last 30-40 years of our life in pain, fear of cancer, etc.

Personally I have a very different set goals and values than the "selfish gene".

Myself I've taken a solemn vow to become the world's oldest living human ...or die trying.

For all we know ageing might be an evolutionary process to free future generations from crappy dictators and absolute rulers.

Let's be realistic here: we're not going to "reverse" ageing.

The article title is unfortunate. A better description of what may be possible, per language deeper down in the article -- and what would be arguably much more feasible -- is "drugs that slow the aging process".

I don't think we are smarter than evolution, in this regard.

Evolution "designed" us to drop off by age 45 or so due to some combination of poor nutrition, opportunistic infections, etc (and other factors, like violence from other humans). Yet we've managed to tweak that built-in expiration date, not just by qualitative factors (like better nutrition, basic healthcare) but to a significant extent by "structural" interventions like antibiotics, antivirals, and vaccines of various sorts.

I suspect that -- if indeed anti-aging treatments become available -- they'll eventually be seen as part of the latter category. As with these, there will be side effects (and just the same, the hope will be they can also be managed).

Eventually, it'll be just another pragmatic thing that people do (alas, the wealthier among us at first most likely).

With that in mind, there's no need to anthropomorphize evolution any more than necessary. It's just a mathematical framework to describe what's been happening over billions of years. There's no hidden "intelligent design" (sorry to use the phrase) behind it, on whose toes we need to be leery of stepping upon.

It may be more helpful to think of evolution as, if anything -- more of a giant hack, on top of an endless series of kludges. Some of which may turn out to be easily patched, or otherwise mitigated.

A species needs to reproduce to evolve and stay competitive, and then at that point they only need to live long enough to reproduce. I presume the lifespan of a species is roughly optimized for that.

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