Forever Young: how one molecule can lock plants in a youthful state (2025)
omnia.sas.upenn.edu
omnia.sas.upenn.edu
Key quote: "permanent juvenility has evolved multiple times", nominally making neotony a more highly evolved and expressly desirable characteristic as voted by life itself.
Now we can say certainly, at least in ancient Australia (if you're a plant): growing up is for losers!
The ones we have planted in our garden will likely need replacing in 7-15 years.
If you study it, it becomes pretty obvious that in most cases reproduction and death are linked. Death is fundamentally a way to optimize reproduction, to control DNA variability and number of offspring.
Also, it is obvious that death has "levels". The cells humans are made of are immortal, in the sense that human cells are capable of living and even reproducing indefinitely, if so directed by DNA. Gametes are meant to survive your death, becoming your children. Now very few cells actually do survive, but that's a constant across pretty much every immortal species. On the other hand, every cell in your body was, in a very real sense, the first bacteria, the first cell ever, billions of years ago. So it certainly is NOT the case that all human cells age, senescence, and die. Only the human as a whole ages, and it is something your cells conspire to do (or conspire not to do, in the case of ovi (~ children), or in the case of cancer cells)
At one point, during the period mammals were all still fish, evolution was still experimenting with death, and so fish have much more variation in their aging and death than mammals do. If you go back further, to reptiles, there's even less death. Most reptiles could be alive for thousands of years (even though the odds are wildly against that). Most reptiles die because of slowly advancing accumulated diseases over time (meaning over hundreds of years, a great many diseases, parasites, even physical damage, ... accumulates. No one cause is really causing their death, but combined they introduce such a strain on the organism as a whole it "dies of old age". Except it's not really of old age in the sense like humans age, it's dying of what you might call 99.9% victories against disease. Eventually the 0.1% damage per incident overpowers the metabolism)
Unfortunately this does mean that death is built into our cells and a lot of processes depend on aging and death. Therefore we are very far away from curing death: you don't just have to fix the mechanism that "ages" our cells, but you have to find alternate ways of working for everything that depends on it. Resetting the clock may be easier, but even the methods that we currently know (ie. regrowing telomeres) have a bad reputation for causing aggressive cancers, and therefore shortening life rather than prolonging it. Plus, at best if you fix aging in humans entirely, we'll be like reptiles. At that point medicine will have to radically change and every tiny trace of every minor infection will have to be treated as a life threatening condition.
Are naked molerats the one weird exception with mammals?
And here's to hoping that the exponentially growing technological capabilities will allow curing death in our (short) lifespans. By God we need that to counteract the ageing population.
But is this life? I'm wondering if an immortal life can be a well-lived life
Why not? It does not mean that we will be some omnipotent god. it just means that we wont age. You can still die from physical trauma, infections, cancer etc. So in practice this would mean that the average human lifespan is not say 70 years, but 120.
I'm pretty sure that humanity will eventually get to immortality (why not? We are already controlling most of our environment) but this will not be like an invention of a magic pill, rather the average lifespan will creep up by a decade or so with every generation.
Now we're at the point where we know whats actively killing you and what to avoid (we can also cure most infections and diseases)
in 30 years most cancers, and likely Alzheimers will be curable too. I'm also sure that lots of aging related conditions will be treatable too (say osteoporosis)
in 60 years we might know enough to start reversing aging effects, and fear of cancer will be a thing of the past, just like now bacterial infections.
.. and who knows when we will start to regrow limbs and fully reverse aging
Well it is probably more life than being dead.
Was there any progress at all so far?
Which mostly causes aggressive cancers.
You can be immortal right now. As a blob of cells in culture.
Immortality has quite a history to it!
Like "in theory there is a valid option but we lack X or Y so far to do it properly"?
You could equally argue that it's a way to optimize lifetime energy efficiency.
> The cells humans are made of are immortal,
Yes but DNA transcription is not error free and most body parts do not grow back after being lost, most perniciously, our teeth. Elephants grow 6 sets of them, but due to their diet, they can end up fully losing all their teeth before they die.
> it's dying of what you might call 99.9% victories against disease
The planet we live on is warmed by the Sun. The Sun's energy can also destroy our cells. It's not just disease.
We are, in some sense, meant to accept the loss of our teeth, likely because it impacts lifetime energy efficiency in some way that we're not correctly observing yet.
(I am aware that natural selection doesn't "want" or "care" about anything. It is just a convenient way to say it).
For instance, the statement:
> it's "an invention".
> As in natural selection decided at one point to introduce death. It really is the case that older lifeforms don't die. All mammals do though.
Natural selection is not an entity. It can not "decide" on anything.
What is here implied is that aging is an outcome of natural selection. Well, aging happens for many reasons, and it depends on how one defines aging (see Tom Kirkwood pointing this out decades ago); the implication meant here is that there has not been an optimisation towards perfection on the cellular (or organismal) level.
So, if damage occurs, the ideal situation would be that 100% of it is repaired. This does not happen. In theory it should be possible, but in actual practice, one will never have 100% repair, both on the DNA as well as protein/cellular level. Mutations will arise - that's for certain. There is no 100% perfect repair system. One can see this today with CRISPR-Cas9 promised as gene therapy tool, but whenever people ask about off-target damage and imperfect repair, those researchers dodge the question completely.
> if you study it, it becomes pretty obvious that in most cases reproduction and death are linked. Death is fundamentally a way to optimize reproduction, to control DNA variability and number of offspring.
I can not agree with this either. There are no specific death genes aimed at reducing life span per se (caspases/apoptosis has many functions, including formation of structure or killing virus-infected cells, among more functions). The main reason why reproduction is favoured, is because this is an evolutionarily stronger strategy, for most organisms. So more energy invested into offspring is more stable from an evolutionary point of view.
> The cells humans are made of are immortal, in the sense that human cells are capable of living and even reproducing indefinitely, if so directed by DNA.
Ultimately all cells are. Otherwise life would not be billion years old. The issue is not about immortality but damage and repair.
For instance, resetting telomeres in humans still would not make humans live thousand of years.
> Unfortunately this does mean that death is built into our cells and a lot of processes depend on aging and death.
No, it is not. What should that be? Describe that mysterious word "death". Which genes are related here?
In theory repair or restoration is possible; it is a finite problem. The question is how long it will take to improve on gene therapy on the nanoscale level. For instance, it should be trivial to enhance CRISPR-Cas9 to eliminate off-target effects; and enforce repair only happens in a guaranteed way. But achieving 100% is very hard - biology is nowhere near as strict as physics. Many genes are transcribed in a leaky manner; that has been one problem in biotechnology and synthetic biology as well. You can see this when you ask the Biobricks guys "which synthetic elements give us 100% control over genetic system xyz". Good luck getting them to commit to giving a single example here.
> At that point medicine will have to radically change and every tiny trace of every minor infection will have to be treated as a life threatening condition.
That's also not logical. If repair or genetic change is 100% or close to 100% accurate, why would ANY "infection" matter? In other words: why would infections be immune from genetic change? ALL viruses/bacteria use DNA or RNA. They are not exempt from ANY change here.
This is why I'm limiting what I mean by death. Specifically to organism-wide senescence, loss of energy, and the death that follows. That senescence is very much programmed into our cells and is something that can be disabled (but as I pointed out, a lot of "downstream" inventions depend on it, so disabling it using current methods has disastrous consequences in practice)
We are also far short of the limits of human lifespan through damage. Old people die from "natural causes". What that is, exactly, is:
Step 1. the level of energy your metabolism produces within an entire cycle goes negative (ie. a 24 hour cycle, so there can be energy shortage during the day fixed during sleep, that doesn't cause this feedback loop to start)
When you're very young at this point homeostasis intervenes and refills your energy stores and go back to stage 1. However, that stops.
Step 2. In order to keep functioning your body effectively disables a system (there's dozens of ways this happens, from lowering blood suger to cutting blood flow entirely), reducing it's energy use. This starts with repair functions, then goes to immune response, and goes from there.
Mostly, at this point, we go back to step 1, and of course you stay alive while the energy level is dropping. But step 2 fixes less and less.
Step 3. Eventually your body has to cut critical functions. Digestion is not the first critical system to get cut, but let's say it is and keep things simple. You can disable digestion. Even just food intake itself (ie. keep water intake going). This will buy you weeks of energy, maybe months. But of course, this eventually causes more energy loss than energy gain.
Step 4. Your energy level drops to zero.
Very disconcerting is that I very much get the impression that moving from step 2 to step 3 is at least a semi-conscious decision. People decide, to an extent, when they die. Or should I say, people can consciously choose to delay it by a few months, at a cost. And certainly, they know pretty accurately when it will happen. I guess I'll find out sometime.
But this is not "damage". This is a combination of feedback loops, the way all "DNA programming" works. DNA has this death programmed in, and certainly in individuals you can achieve better outcomes by intervening externally. The time it takes for the mechanism to fire is also a parameter in our DNA, and obviously, the only way to implement this is with some sort of clock. Telomeres are thought to be part of the clock mechanism that does this, but they can't be the full answer.
Now you can say this is not "causing death". If anything, this is preventing it. And except for one major detail you're kind of right. That major detail is that increasing energy output is trivial, yet the system stops doing it (permanently increasing energy output is what happens during growth and temporarily increasing energy output is what happens during early aging). Your body restricts itself from that solution to the point that average energy use systematically decreases during your life after a certain point and that is what finally leads to a natural death, what finally fires off steps 2 and 3.
I don't claim that if you fix this there wouldn't be other problems, such as DNA damage, which would require their own solutions (even though we have that too. Crispr-CAS is restricted to short changes. But you can write an algorithm that, by combining literally tens of thousands of little Crispr-CAS cuts, repair essentially any DNA damage. And while that is probably not good enough a solution, you can easily demonstrate it works. Not working well enough, but working)
However, finding ways to do large scale fixing of DNA damage makes little sense until we can reset or disable the death clock.
> No, it is not. What should that be? Describe that mysterious word "death". Which genes are related here?
There are a great many genes involved, and many more regulatory factors. That's the problem. If it was one, "fixing" it would be easy. A famous example is p54, which puts a sort of absolute limit on cell age (when it fires, it activates other proteins that destroy the DNA, it fires off the self destruct mechanism of mitochondria and it rips open the cell membrane). There are also highly regulated genes that delay death under specific circumstances, like TERT changing the time at which such mechanisms will fire during cell division, for example.
> what happens to organisms outside their reproductive cycle is pretty much irrelevant to natural selection
Certainly seems plausible for that to create evolutionary pressure: why have organisms still consuming resources if they're no longer contributing to reproduction / natural selection?
Of course there is. Without death, no natural selection. First, obviously, it gives precedence to children, who by definition are more evolved than parents. Now of course, you could say that accidental death is sufficient. But is it? Good question.
In practice there also appears to be evolutionary pressure for death to exist. There are very large, very old organisms alive on earth. Organisms old enough to have been alive when Jesus was born, when the Pyramids were built, organisms old enough to have "met" Neanderthals. Aside from a few individuals they were outcompeted in their native habitats.
https://en.wikipedia.org/wiki/Largest_organisms
They don't reproduce very much at all, and they're not very resilient as a species. The theory is that the parent organism occupies the entire habitat, and so reproduction fails. Then, at some point something happens to the organism as a whole and the entire species dies.
So, yes there appears to be evolutionary pressure to die. Ironically, the vast majority of large organisms that die of aging live longer than immortal organisms.
I mean, mutation and damage are different sides of the same coin. Without change you don't have evolution.
How so? Snakes only live like 30 years. Tortoises are long lived, but it is low hundreds years, not thousands.
And it causes the ovi to start the cell division that will create the next generation, form the "yellow body" and then effectively disconnect from the baby girl's body (obviously that cell division doesn't complete until a sperm combines with an ovi, hopefully multiple decades later)
So normally, this happens immediately after birth, together with dozens of other big changes.
Also, there Henrietta Lacks, died in 1951 of metastasized adenocarcinoma, but "still alive":
Further those cells can’t compete out in a forest somewhere. Going multicellular means optimizing in ways counterproductive to survival on their own. But failing to cull off defective cells means you can’t have a functioning multicellular life form, thus making this a dead end.
So no in nature there isn’t some switch that means those cells get to survive indefinitely. The closest viable option is as an infection shared among very closely related organisms, but that’s not a stable option which means it’s really rare in nature.
As a kind of immortality, yes. It's not even just DNA, it's actual cells that were part of the individual that stay alive beyond any age limit.
Does it keep the full individual organism alive? No.
> actual cells that were part of the individual that stay alive beyond any age limit
Neither the egg or sperm or egg cell survive to birth. Only descendent cells with wildly different DNA do.
Close to 100.000 cells make the reverse change, in girls (they become egg cells, and potentially the next generation). There's a continuous cycle keeping (some of) these cells alive. A cycle that has been running one way or another, for 4.3 billion years.
Like you can apply the word “same” if you want, but what’s actually happening is isn’t a simple continuation of the original organism any more than a clone is the same organism and at least that’s more closely related genetically.
If John and Mary were first, how long until everyone is a descendent of john and Mary?
Huh?
Fish came before reptiles.
So these two groups came after fish.
https://bio.libretexts.org/Bookshelves/Introductory_and_Gene...
Don't stop at the organism level. Your body is made of cells, cells are made of organelles, etc., but society/culture/language is made up of individuals, and those higher-level entities also compete and adapt and flourish or die. It's natural selection all the way...up
Yes, you really can't help but feel the whole Wolverine saga part of Marvel Comics just doesn't make any sense!
That’s fine - we just need to find a way to slow aging and wait until science advances. Strictly speaking we just need to find a way to keep our brains alive and stimulated, not the whole body.
Not weird at all. You sort of need this if evolution is to do its work... otherwise offspring must out-compete its parents and grandparents, who long ago colonized all of the good niches and left nothing for anything else. They'll die eventually, of course, but they'll almost certainly take the entire species with it because they were unadapted for changing conditions. Death is flexibility on an evolutionary timescale, and immortality is rigidity.
cars that move with electricity, little helicopters with 4 motors that can hover easily, small cheap computers on one board, ham radios with computers that everyone carries now.
Also, I find the kind of language you're using really grating. The attempt to mystify modern technology in order to strike awe always backfires. Yeah dude, I know what a cell phone is. Sure, they're very cool. But what's the argument you're trying to make?
The only distinction I would make is that "pure science" has also produced many additional findings that are not immediately useful to me today, but some of them might be in the future. (And that's the only prediction I'm making about the future in this entire thread.)
That's why I bristled at the whiggish march of progress you depicted. You can believe that science is an ever increasing grasp of the truth without being naive about what the outcome of that knowledge might be. We could all still nuke ourselves into oblivion, in the most extreme example.
I know people hate that kind of doom and gloom. I'm just saying that, when you make the jump from "wow, science is amazing, look at what we've discovered" to "wow science is amazing, look what technologies it has unlocked" you are implying an inevitability to technological progress that does not exist.
But the original post said "science does not provide the kinds of answers people want." I think what most people want from science is to have better things, or less disease and misery. I would argue that it has done a lot of that in our lifetimes. That doesn't mean everyone is spiritually fulfilled, nor does it mean that we won't nuke each other. But it has done real things that make our lives much better.
that's why slavery is obsolete, we didn't need them anymore post industrial revolution
machine can work 24/7 and have infinitely more scalability, do you think we can harness planetary level of energy using human ?? I dn't think so
also one biggest part is predictability, human varies by value of work they can provide. with machine you can have one spec sheet and done with the day
You would have to move every electron traveling in between each neuron into exactly same place, same momentum etc. All of them in the same time obviously. I stress the word move. In a system that is constantly moving on molecular level at crazy speed. Even that is only valid in case our consciousness is just electron cloud at given moment travelling in the brain. Maybe its more, all interconnected.
How you want to move that. The science for that won't be around for millennia, if ever (there may be quite hard constraints on quantum level in similar way speed of light is hard limit for Star trek utopias, universe doesn't rearange itself and change its laws just because of our emotional wishful thinking). Once we can do that, it means we could mess with telomeres, DNA etc with 100% precision and knowledge so this will be a moot point. Don't hold your breath for this.
This is still within the science fiction territory, but much more realistic than fixing aging or an actual teleporter.
The brain would still be old, but it would probably benefit quite a lot from the new body's youthness.
Bacteria do that in ~hourly intervals, humans take decades, some plants can span millenia.
So you could say the 'update interval' is tuned to how fast-changing a species' environment is. A balance between energy 'wasted' on re-building individuals from scratch, vs wasting energy by having poorly adapted individuals.
So 'immortal humans' to me reads as: humans optimized for a caveman hunter-gatherer lifestyle, while living in Star Trek like tech-heavy surroundings.
If anything, humanity would be served by shorter lifecycles, until tech advances stabilize somehow (?). Okay a few individuals living way longer could be good. Eg. billionaire tech bros taking that spot? Please nooo!!!