So the ancient mystery of why we need sleep might have just been answered.
The paper shows that cellāautonomous mild uncoupling in Drosophila sleepāinducing neurons -- via Ucp4A/Ucp4C -- keeps the flies awake by lowering mitochondrial Īp and therefore electron leak. This suggests a biochemical rationale for sleep -- which is postponed by the uncoupler. That form of pharmacological manipulation is also a very local intervention and likely has never been tried in mammals. (Most mitochondrial uncouplers aren't that specific and don't cross the BBB very well. Even "safe" new ones like BAM15.) If the paper is correct, not only is the mystery solved, but "healthy" wakefulness-promoting drugs might be on the horizon.
I'm curious about what this means for deep vs. light sleepers, and for people who need more or less sleep than others. Perhaps those traits are modifiable.
> So the ancient mystery of why we need sleep might have just been answered.
I would be very surprised if sleep would serve only one purpose. In complex interconnected systems you usually don't get far with monocausal explanations.
TFA also acknowledges this:
> There could well be many other functions that have since joined in with the sleep cycle (such as memory consolidation), but the authors hypothesize that mitochondrial function is the process that underlies all of them. If you need oxygen, then you need sleep!> If you need oxygen, then you need sleep!
Do plants sleep? Don't some insects, like flies, live without any sleep?
It would make sense if there was a monocausal explanation of why ancient ancestors started sleeping, but then other body functions started making use of the sleeping system since it was at hand.
> why ancient ancestors started sleeping
I tend to believe that our ancestors didn't start sleeping, they started waking up ! the default pattern is sleep and conservation of energy, but you need to wake up to expend more energy for a short period in order to feed yourself efficiently
Hey, that's Hyrum's Law!
Sounds like my microservices
It might have one evolutionary root cause and then got hijacked for other uses as well.
AI frenzy almost convinced me that sleep was the training of our neural network with all the prompts of the day.
And now this /o\
That's what I still 'believe'. Wake-sleep algorithm [1] is a good start for speculation. I think brain needs to be in a different mode to reorganize its weights and to forget unnecessary things to prevent overfitting. In this mode we happen to be unconscious. I also believe dreams are just hallucinations caused by random noise input to the system. The brain converts noise distribution to a meaningful distribution and samples from that. I have zero evidence btw, but I believe these are related.
Curious how the zeitgeist changes, on a previous AI cycle we could thought sleep was required/generated by a semi-space garbage collection brain-LISP process :)
> sleep was the training of our neural network with all the prompts of the day
Periods of sleep certainly seem to be used in that sort of way, but that is an extra use evolution found for the sleep cycle once it existed rather than the reason sleep developed in the first place.
There are a number of things that seem tied to, or at least aligned with, our wake/sleep cycle that likely didn't exist when sleep first came about.
You didnāt need this study to realize that this was wrong: jellyfish and hydras also sleep despite not having a central nervous system. There are indications that sponges sleep too, despite not having any neurons (though obviously itās somewhat ambiguous): https://www.science.org/content/article/if-alive-sleeps-brai...
> So the ancient mystery of why we need sleep might have just been answered.
No, science doesn't work that way. The ancient mystery of why we need sleep has a new theory [1].
[1] I am assuming it is new. It might actually be old. I don't know.
I don't think GP was rigorous, but your comment is kind of pedantic, isn't it?
Most people commenting here know that all models are false but some make good predictions, and achieving that status is enough for most laypeople to classify it as a (potential) answer.
Going further, yes, this is a new theory among others, but afaik is the first one with strong evidence.
I don't mean it as an attack on GP, but no, I don't agree that this is pedantic. This happens constantly when science is popularized -- people read one article and leap to the conclusion that a problem has been revolutionized/solved/answered simply because they're reading about it -- and no, the HN audience is no better. Technophiles love a good scientific revolution story.
It's very much a fundamental misunderstanding of how science works. Almost nothing in science has an answer, and if you let your brain lock in that way, you forego the opportunity to ask interesting questions. It also leads directly to lots of downstream pathologies common in amongst laypeople (e.g. "The Science is Settled", which it almost never is).
> Going further, yes, this is a new theory among others, but afaik is the first one with strong evidence.
I am not an expert in this field, but others have evidence too. Particularly when asking "why" questions like this, the bar for proof is incredibly high.
a completely unnecessary interjection
"might have been answered" is absolutely valid: the correct theory might have been produced
On the contrary, this is such a common misunderstanding that it practically defines the meme of pop science.
Proposal of a hypothesis is not answering. Even if, decades from now and after many additional studies, scientific consensus settles on this hypothesis as "the answer", the first paper to speculate about the idea is still just a speculation. Moreover, if you're an outsider, the speculation is often an idea that's been floating around the field for longer than you've been aware of it.
Basically, just abandon your notion that there is "an answer" to any sufficiently complex scientific question, and you will be better off.
This seems like a plausible evolutionary reason for sleep to start existing but humans use sleep for plenty of things besides this, like moving declarative memories form short to long term memory in spindle sleep or consolidating procedural memory in REM sleep.
> So the ancient mystery of why we need sleep might have just been answered.
There are layers to this, some of which are definitely not ancient mysteries. We sleep because the environment has a day-night cycle. If any task an organism must perform is better done during the day, then evolution has a very clear gradient towards only doing that thing during the day. That leads to doing other things at night, since it would be comparatively advantageous to do them at night, given whatever task is most benefited from being done during the day.
If there wasn't a day-night cycle it's unlikely that the brain would have evolved to crucially depend on approximately a night's worth of time of not using the body.
The question isn't the timing but why it happens at all. Even at night, being unaware of one's surroundings during sleep is a huge disadvantage that requires lots of effort and adaptation to work around. It needs to produce commensurate benefits, but we're not sure what they are.
Exactly! Going offline for hours every day in an adversarial world is positively nuts! The reason can't be idiosyncratic. No gentle gradient of comparative advantage can rationalize it. It must be something severe and nigh impossible to do any other way.
Furthermore, sleep is very specifically about the taking the brain offline: that's what deteriorates first in the absence of sleep and the tortured workarounds for animals that absolutely must avoid sleep (e.g. migratory birds) involve sleeping part of the brain at a time. Any explanation that isn't highly specific to the brain's responsibilities has the immediate hurdle of explaining this away, and for that reason I don't buy the mitochondrial explanation. Mitochondria are too universal and sleep is too specific to the brain. Energy is fungible, so I don't buy that nature wouldn't figure out the "trick" of having a subset of the mitochondrial population sleep at a time.
My money is on the "brain algorithm" requiring an online/offline phase, whether that's contrastive learning or memory consolidation or something else. There are lots of candidates for fundamental brain algorithms with the "feature" that they require an offline phase that cannot be incrementally worked around, and these fit the observations much better.
I will admit I'm mostly ignorant on these subjects, but just using rational/logic
> If any task an organism must perform is better done during the day, then evolution has a very clear gradient towards only doing that thing during the day.
But wouldn't remaining conscious and aware be the optimal state? So you don't get eaten by predators or attacked by other humans etc? It seems to me your sentence points to an ultra low energy but conscious state, not one in which you're very vulnerable...
But maybe the vulnerability is just too little, maybe cooperative tribal/family type arrangements covered this sufficiently to not be selected?
What you say is true and fairly obvious, but the interesting mystery is the mechanism of that dependency, not its evolutionary advantage.
Knowing the mechanism opens the door to medical interventions. Analogously, no one is confused as to why the human body stores fat and gets hungry, but knowing the mechanism allows weight-loss treatment like Ozempic.
the interesting mystery is the mechanism of that dependency, not its evolutionary advantage.
Nah, I'd say the evolutionary advantage is the more interesting mystery. The mechanism is just an implementation detail, after all.
And by the way, if we tamper with something without understanding its purpose we risk messing something up.
Not sure anybody is disagreeing with this. Yes, evolution, day night cycles.
The point of this is finding the 'mechanism' which evolution came up, and now we can manipulate it to fit the modern world and stay up at night.
It's interesting that sleep is controlled by mitochondria, but sleep is clearly involved in learning, and whatever algorithm for intelligence the brain does. Do those algorithms still work if you intervene at the level of the mitochondria? Or are the mitochondria just a good way of measuring elapsed time through energy expenditure? e.g. The algorithm needs a sleep phase to run roughly every x neural firings, or performance degrades and mitochondria were available as measuring devices when nature needed a way to guess how long the wake phase had been running.
Maybe you could intervene to prevent anyone from feeling tired, but would the learning algorithm still work? That part is still a mystery.
"electrons flow through the respiratory chains of the respective feedback controllers like sand in the hourglass that determines when balance must be restored"
Wow, that is my new favorite sentence from any paper ever, replacing Mark Thomas' equally epic: "What it begins to suggest is that weāre looking at a Lord of the Rings-type world" from the legendary meeting at the Royal Society in London 2012/13.
Perhaps sand won't save you this time, but this sand will save you time.
The paper is here:
https://www.nature.com/articles/s41586-025-09261-y
Not an expert in this area, but the essay feels a bit like an oversimplification. Not only is this in flies, but I wasn't entirely convinced this isn't about rest rather than sleep per se. It's a cool paper, interesting to read and read about, but my hunch is there's more steps in the chain, and am not sure it will replicate in humans or even mammals. But maybe I'll be wrong.
It is an awful paper and I am a very expert in this area. This is science, alas.
Huh, you actually are an expert in this area. Iām curious to hear more too.
> There, I studied the early stages of neuronal development in the Drosophila embryoā¦ > I graduated with my Ph.D. in September 2006 and decided that I would continue my research activity on sleep, using flies as the animal model.
Not an expert, but Iād love to hear more about what makes it awful.
Please elaborate.
Could this be an explanation for why people who go without sleep for long enough eventually just die? The Guinness Book of World Records doesn't accept records on staying awake for the same reason they don't accept records for the longest game of Russian Roulette.
While it is true that Guiness stopped keeping track of records of staying awake for health reasons, people with severe sleep deprivation ends up being psychotic and admitted to psychiatric care and administered sleep inducing drugs. So, lack of sleep is not something you die from short term. Long term (years, decades) short sleep is associated with higher all cause mortality risk though.
I'm getting this from the book Why We Sleep by Matthew Walker. There were some other exaggerations in the book that people have noted, though, so maybe I was too trusting of this particular fact.
there's this prion disease https://en.wikipedia.org/wiki/Fatal_insomnia
Something I thought was just an internet tale: mitochondria are close descendants of bacteria, and so taking antibiotics will potentially harm them. But turns out this is actually rooted in science ...
It's specifically Quinolones which can harm mitochondria. There's no ongoing concern for something like Penicillin. We also shouldn't expect there to be mitochondrial risk from a fungi-derived chemical like Penicillin, since fungi also have mitochondria.
In general you want the weakest and most targeted antibiotic for the job. Most people will never need a Quinolone, and you should be skeptical whenever sophisticated antibiotics are prescribed. Why not Penicillin? should have an answer involving the name of a bacteria, not the doctor's personal preference, or a relationship with a company.
https://en.wikipedia.org/wiki/Quinolone_antibiotic#Cellular_...
> Most people will never need a Quinolone
At least in Germany eye doctors are very happy to prescribe them. It's "only" eye drops, but it is (for laymen) almost impossible to find information if they are also dangerous in this form.
Be very careful when stating this kind of thing. It's extremely easy for people that already have a hard time understanding science and medicine to take this as evidence to support their anti science and anti vaccine/medicine.
Different antibiotics target different cellular mechanisms depending on what the microorganism is. And almost none of them target the mitochondria at all.
Yes the common hypothesis is that mitochondria were originally a symbiotic separate organism that joined the cells that eventually became the origin of most complex life.
Remember that if that's what happened, it was over 3 billion years ago. After that immense amount of time, mitochondria aren't really separate organisms anymore. They're deeply entwined into every complex organism in the world. Very unlikely for common antibiotics to have any effect on them at all.
It does appear that this can be a problem.
This paper is focusing on ribosome inhibitors like tetracycline.
Increasing the count and efficiency of mitochondria is gonna be a big deal. ME/CFS is caused by these organelles not working as they should.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Highly recommend red light therapy for this. There's a spreadsheet that contains [1] all the scientific research does on effect on mitochondria.
[1]: https://docs.google.com/spreadsheets/u/1/d/1ZKl5Me4XwPj4YgJC...
Isnāt simply getting enough outdoor sunlight just as good as red light therapy.
Thatās a long list. Not all research is good research, or shows the effect youāre looking for. Where did this come from?
Do you use red light therapy? For what? How often? Where do you focus it? I did manage to get some red light masks although I find it hard to fit into my routine
Iām already getting a lot of (subjective) benefit from doing what I can with supplements that target each phase of the Krebs cycleās bottlenecks, and glutathione production to delay ROS damage (which this paper finger-points at). My mental endurance to do things like program and handle corporate politics lasts hours longer on days when I do this.
Next I need to get a lot better cardio endurance but I have some pulmonary problems to deal with.
Anyone interested in this should look up "MOTS-C" and "SS-31".
They're readily available online. Both of them are peptides that enhance mitochondrial function.
MOTS-C in particular is very fascinating.
I have a vial of 20mg I've yet to use.
Sleep is super important. Iāve seen too many workaholic types that barely sleep. So many of these folks end up with serious issues later in life.
One best things about getting laid off from work is that one get to sleep as long as one want in the morning!
I don't think this person has children :P
Yes, thatās the ālayā that you will be doing.
Or binge watch the entire Walking Dead series in a month
Workaholism is always just manifesting underlying psychical issues, be it some form of OCD, deep unhappiness with one's life and escapism from emptiness or similar. Such state manifests in many destructive behaviors, which then like in case of sleep create their own forces of destruction.
One can't escape psychology, one thing no school taught me (and they should have since we all deal with this in some way! plus its not that complex). Once I grokked the basics, dealing and with people and understanding them became much easier.
I'd be careful with saying that is "always" the case.
What about people who are deeply passionate about their mission and chose to devote their life to it?
[dead]
Maybe some people just enjoy working.
Being addicted to workahol means they aren't able to enjoy other things. Your comment is like saying "maybe alcoholics just enjoy drinking".
There is a difference between being physically tired as a result of metabolic effort, and being mentally tired/sleepy. Even if you lie on the couch all day you will still be tired come night time, and can not survive for long if deprived of sleep.
It seems the mental need for sleep comes from the brain needing offline (no sensory input) downtime for "housekeeping" activities - perhaps essentially organizing and filing away the day's short-term memories.
the brain burns more power when doing mentally exhausting tasks than at idle, so it makes sense to have to recharge mitochondria in there. (the 'more' is not huge, like 5% - so it also makes sense to be tired after a lazy day I guess)
But we're sleepy every night regardless of how much or how little we have done mentally during the day. Doing more work (mental or physical) than usual will make us feel more tired, but the basic need for the 24hr sleep cycle is there regardless.
We fundamentally sleep at night based on circadian rhythm (evolved from earth's 24hr day), not based on activity level. We do also feel tired after a strenuous activity, but recover after a little rest and nutrition - this doesn't appear to be the same thing as the fundamental need for sleep.
The body expends 2000 calories of energy (via mitochondria) simply to be alive, even if you lie in a hospital bed and are unconscious. You do a marathonās amount of work every day. You need to sleep to deal with that.
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