So the ancient mystery of why we need sleep might have just been answered.
The paper shows that cell‑autonomous mild uncoupling in Drosophila sleep‑inducing neurons -- via Ucp4A/Ucp4C -- keeps the flies awake by lowering mitochondrial Δp 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.
> 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!
I think it should have been “If you need oxygen and have a CNS, then you need sleep.” Other tissues can take oxidative break during wakefulness, but since CNS is _generating_ wakefulness, if it takes a break, by construction there is sleep.
I would be surprised by any organism that can sense its environment and doesn’t change behaviour at night. The difference is pretty extreme, whether its temperature, light or just all other beings changing what they’re doing. Even if you don’t notice yourself, you’ll probably be affected by second-order effects.
> Across the animal kingdom sleep satisfies most, though not necessarily all, of the following criteria: (1) decreased brain arousal and its behavioral correlate, decreased responsiveness to an animal’s surroundings, which distinguishes sleep from immobile wakefulness (also known as rest); (2) electrical changes in the brain’s activity patterns relative to the waking state; (3) behavioral quiescence, often accompanied by a preferred location and characteristic posture; (4) rapid reversibility, which distinguishes sleep from hibernation, anesthesia and coma; (5) homeostatic regulation, in which lost episodes of behavioral quiescence and low arousal are followed by compensatory (rebound) episodes [10].
And you don't think different criteria might apply to plants? I mean, look, we are just discovering how plants function as a society. They are immobile and 4 and 5 might be caused by the fact that an animal is mobile, at least for the most examples, but where not, it can at least react in some manner. Plants have a very very slow reaction time so to them 4 and 5 don't apply even in waking condition, I mean unless you consider several hours to be a reaction. Let's be frank: we don't know (yet).
What I don't appreciate is an outright dismissal "plants do not sleep".
We know plants have a diurnal cycle and react to sun/day and some visibly change between night and day. If we say that one of these states is less active, we may decide to call it dormant. Dormant comes from latin dormire, which is sleep. So... why not?
They need oxygen for the mitochondrial electron transport chain to produce ATP. The vast majority of multicellular organisms need oxygen for that reason, and I can count the exceptions on one or two hands (i.e. Pogonophoran tube worms, some anaerobic sponges, a few parasitic helminths).
Plants respire oxygen continually, day and night. It's a myth that they only respire at night.
Like every other organism except for anaerobes (mostly microbes, some fungi) they need oxygen in order to burn fuel for cellular processes. Plant cells are doing things day and night.
The origin of the myth is simply that they produce more oxygen via photosynthesis than they respire, and so are net producers of oxygen during the day.
But their cells still consume oxygen during the day, don't they? In sunshine they produce more oxygen than they consume, but the cells are still fundamentally powered by mitochondria oxidizing glucose
Plants have chloroplasts that produce oxygen and sugar. But plants also have mitochondria that consume oxygen and sugar and run many of the same metabolic functions as in animals.
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.
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
There definitely was never a life form which exclusively slept - all the critical parts of life require being awake. Life that didn't sleep, however, is possible.
I don't think they meant "Modern" sleep. I think they meant "Only brief periods of highly energetic activity before returning to the usual activities were precursors to our modern consciousness/wakefulness"
That is also what I am referring to. Energetic activity is required to live and to reproduce, those are the normal activities. An active creature may have evolved a state of dormancy for various reasons, but there was never an organism in a state of pure dormancy.
Yea, but at some point this is probably gonna strain the colloquial definition of sleep. So I went for one of the oldest and perhaps simplest animals around, to examine the "creature" angle in extrema.
Maybe not 'exclusively' slept, but koalas[1] sleep for a majority of the day (16-20 hours) in order to digest highly toxic eucalyptus leaves which constitute the main portion of their diet.
By animal standards, plants are permanently dormant. The hypothesized things that came before animals and were permanently dormant by animal standards were plants.
Yeah. Perhaps animals are the first organisms that developed the ability to be awake, not the first that developed the ability to sleep.
By the way, even Cnidaria (jellyfish etc) exhibit sleep-wake cycles [1]. They don't have a brain, but they do have a nervous system. Maybe the first animal with nervous system (a common ancestor of Cnidaria and Bilateria) was the first to have a sleep-wake cycle.
I don't understand the current research on mitochondria, but it sounds as if sleep has to do with how neurons work.
That's actually very interesting. The most convincing explanation for also I've heard is it's just a result of living in a planet that is cold and dark half of the time. It makes sense to use that time to recharge. I wonder how much sunlight would factor in for something like a jellyfish.
Sleep is still detectable via CPU load, so I added a thread that checks for load and runs some critical cleanup processes when it drops below a preset threshold.
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.
When we don’t sleep, we can lose sensory and cognitive coherence. Mild visual hallucinations begin and reality can start slipping.
Sleep itself is characterized by coherent neural activity— the large number of brain regions with synchronized neural activity. The slow waves where huge numbers are all firing close together in a rhythm. Low frequency and high amplitude delta brainwaves (1-2 hertz).
Complex adaptive brain activity requires more complex firing than a simple rhythmic frequency. So, in a way, the complex activity must be stopped in order to support global synchrony.
Why would our neurons want to all fire synchronously? Well, it is healthy for neurons to fire together in a causal manner— neurons release growth hormones then. That neural growth during synchronized firing is the basis of “neurons that fire together wire together.” And it doesn’t seem coincidental that a successfully predicted model feels good, as in the case of successfully throw a ball in a basket. Neurons are trying to predict other neuron firing and respond to it. If they are unable to effectively, they may become like the 1/3 of our baby neurons in the cortex — they will be pruned and die.
Good feelings is positive reinforcement—behaviors leading to good feelings get reinforcement. The feeling of harmony or harmonization, where we have to balance a broad set of internal neural impulses, feels good when we do it well. We feel harmony in music — and in our own internal sensory resonance to the world.
Hypothesis 1: the harmonization of neural activity might cause conscious feelings due to the convergence of the activity to platonic forms (see Platonic Representation Hypothesis in LLM research).
Returning to sleep — this is a proposal for why sleep feels good. Synchronization might intrinsically feel good. But because the sleep also disrupts your working memory contextual attunements (ie, whatever your day was about) - taking your brain into deep synchrony — it strengthens the overall dendritic connections between the synchronizing neurons.
And, because it wears off the edges of your previous experiences — you can return refreshed.
In this way, sleep seems to contribute to the overall integrity of the operation of our intelligence. Without it, we lose integrity and internal harmony.
And yet, not sleeping is one of my favorite drugs. Can be a major performance enhancer, even if it is variable.
Hypothesis 2: Not sleeping increases the (statistical) temperature of the brain.
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 didn’t 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 it’s somewhat ambiguous): https://www.science.org/content/article/if-alive-sleeps-brai...
Philosophers of mind have always tried to describe the brain using contemporary technology analogies. It's only natural and nothing to frown at.
Descartes compared the human mind to waterworks and hydraulic machines, other authors used mechanical clocks, telegraph systems, digital computers, and (in the recent decades) neural networks.
In the end it's all computing and to a degree all of those models serve as good analogies to the wetware, one just needs to avoid drawing wild conclusions from it.
I'm sure there will be new analogies in the future as our tech progresses.
We don't literally train on today's prompts while we sleep, but there actually _are_ some _computing_ tasks going on in our brains at that time that seem to be important for the system.
Indeed. Animals without linguistic ability (like fruit flies) need sleep, but after ChatGPT's release in 2022, now tech bros think LLMs specifically might model the animal brain in general because of anthropocentrism and anthropomorphism.
It's also a fundamental misunderstanding of how LLMs work, mixing up inference with training.
Come on, don't be uncharitable, language isn't inherently necessary for models like LLMs, you can train something similar on visual inputs. Fruit flies have neurons that pass around ~probabilities/signal strengths to each other to represent their environments and basic concepts, it's not way off as an analogy.
The statement was "AI frenzy almost convinced me that sleep was the training of our neural network with all the prompts of the day."
Prompts are specific to LLMs. Most neural networks don't have prompts.
Additionally, prompts happen during LLM inference, not LLM training. There are many non-technical people who claim they have experience "training" LLMs, when they are just an end user who added a lot of tokens to the context window during inference.
> There are many non-technical people who claim they have experience "training" LLMs, when they are just an end user who added a lot of tokens to the context window during inference.
Since in-context learning is a thing, “adding tokens to the context window”, at least with the intent and effect of having a particular impact on capabilities when inference is run on the context to which they were added, is, arguably, a kind of training.
Sure. Foundation models aren't fine-tuned, and companies fine-tune foundation models to optimize user experience. So they are modeling the animal brain on an even more specific type of LLM that happens to be related to being a consumer of AI products.
You're being pretty pedantic about the specific term used. Everything they said makes sense if you change "prompts" to "training examples" and you wouldn't expect someone who hasn't implemented an AI model to know the difference.
It's like someone said while driving the car "let's give it some gas" and you said "but the tank is almost full" when they obviously meant "let's press the accelerator pedal"
Funnily I am interested in this semantic argument.
Do LLM trainers actually feed their « beast » with prompts from the past? Especially ones that are human corrections upon false assumptions hallucinated by the LLM?
As a non-specialist I would definitely see a lot of value in doing so, but I let you, experts, clarify that point.
I feel this too, and always wondered if it related to the glymphatic system [1].
This is the system that clears out metabolic waste from the brain which builds up over time, and it's theorized that during slow-wave sleep in particular, the slow waves help pump out this waste fluid through microscopic channels the open up.
AFIAK, there were some researchers that were wondering if a drug of some kind could force this to happen more quickly, thus cutting down the amount we need to sleep. (Probably a bad idea.)
> it feels like there is poison built up in my mind, then sleep clears it up/feel better.
I'm not sure how common this is, but I feel this acutely after sustained mental exertion (e.g. reading informational material for a few hours). A deep 15 minute nap takes the feeling away completely without any grogginess.
Almost the same here but it's not a deep nap for me. I relax, start seeing dream-like images in my mind (yet still drifting into-out of conscious awareness), then in ~15 minutes I feel energy build up and am ready to jump up and go.
I would say that the darn alarm clock prevented me from completing a sleep cycle properly in the morning, and now I did complete it and made my brain happy.
How do you ensure you are asleep for 15 minutes? Do you have a smart watch that detects when you drift asleep and can start a timer then? Or are you not losing consciousness, but are you simply closing your eyes and meditating?
For these instances where I get urgently fatigued ("brain tired") in the daytime, I close my eyes and fall asleep in 1-2 minutes. I'm definitely unconscious. I don't set any alarm and naturally wake up in ~15 minutes. It's been as short as 8 minutes, or as long as 30, but probably averages around 15. "Body tired" is different and requires the normal multiple hours of sleep.
This is something I have considered getting into where and alarm goes off from when you actually fall asleep. For me it seems 5 hrs of sleep is the sweet spot (functional, slightly sleep deprived, but motivated)
I wouldn't. The current theories on sleep and "brain needs sleep" always struck me as a stopgap theory. Even spent some time with GPT arguing about it and never felt fully convinced, like the real reason was still missing.
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.
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.
It might not be intended as an attack, but it does feels like one (especially that unnecesary jab at technophiles). Also I find it incredibly ironic that you are making so many assumptions about what GP meant, what HN audience understands from the article and what they will make of it just to make a point about philosophy of science and popsci.
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.
It sounds like you're just dead set on defending the rude way of dismissing someone's comment? "Might just have been answered" is a completely valid description of what happened: the correct hypothesis might have been produced. It is obvious to anyone that it still requires verification; producing an answer is not the same as proving it beyond a shadow of doubt, and no one said it was. You're pretending to debate some philosophy of science but actually are playing pedantic word games to sound smart or gatekeep or something.
> 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.
> Mitochondria are too universal and sleep is too specific to the brain
The brain has uniquely high specific power requirements per gram of dry weight. Not even the heart is this power-hungry. This surely places a lot of uniquely high metabolic stress on the neural cells.
And neural cells are long-living, so they can't be easily replaced throughout the lifetime. So their housekeeping has to be very thorough, carefully cleaning up all the waste products.
Mitochondrial dysfunction literally leads to Alzheimers, dementia, etc. The link is clear as day - don't sleep, lose your mind. Put a different way, life rusts (oxidizes) your brain, and sleep de-rusts it. And unfortunately I'm still someone who regularly pulls all nighters because of a combination of disorders, ADHD and sleep cycle issues. I'm killing myself rather prematurely. But then, all addictions tend to do that and tend to be things the addict has trouble controlling. :(
Also, the theory would better be expressed as "all mitochondria require rest, neuronal rest in the brain looks like sleep (but many cells in the body also get quite a bit of rest during this time)" - so many people here seem to be getting this backwards thinking sleep is the special thing - it's one way large scale mitochondrial rest (as well as lots of other important co-occuring processes) presents in the brain.
The really interesting question is... how do heart cells do it? Because they're a clear exception to this theory... Lactate?
I mean, it still can be idiosyncratic if the local maximum is steep enough. Identifying and signalling subgroups of mitochondria in a cell to put on pause might be prohibitive, for instance, and would still reduce the power available to that cell.
Or maybe going all the way on and mostly-off with your mitochondria, even specifically with your brain mitochondria, really is that much more efficient than having half of them offline (but still consuming energy for upkeep) at any time. The brain is a big ol energy hog, after all.
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.
If the brain fundamentally needs sleep then we'd sleep regardless, just not aligned to the day-night cycle. There's quite a bit of variation in sleep patterns and amounts between different animals. Chinstrap Penguins only sleep a few seconds at a time, but still manage to rack up ~11hr sleep in a 24hr period! Elephants only sleep for ~2hr/day, horses for 3hr/day.
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.
There are also other reasons for sleep, like cleaning up neurotransmitters and stocking them up in advance. I would guess it's a more immediate trigger?
That's a good point. Maybe we found the mechanism to stay awake, but if that doesn't also translate to normalizing everything else that happens while sleeping, then who knows. Maybe people turn into wide awake zombies after a few days.
Piggybacking off this, for a more general reason for sleep:
"My definition would be as follows: sleep evolved as a species-specific response to a 24-hour world. During sleep – a period of physical inactivity – individuals avoid movement within an environment to which they are poorly adapted, but then use this time to undertake essential housekeeping functions demanded by their physiology."
From Life Time by Russell Foster. Still one of the most lucid and well-written books on sleep I've ever read.
It's good to know but the practical applications may be limited. Once we finally figured out why/how we use oxygen in the 1930s, it led to a couple applications, like anesthesia regulation and hyperbaric oxygen therapy. But there wasn't a lot you could do with it. We've probably gathered all the information about sleep that has practical applications, and a lot of it has to do with other things like hormones, sensory input, age.
I'm curious how the few famous people that do not sleep at all, what's going on in their biochemestry? I don't mean celebrities, there are a few people who became famous because they do not sleep. They hold 2 complete careers, one during the day and one at night to keep from getting bored.
I don't think any of those actually do not sleep. They probably sleep less than normal and skimp on sleep, but i have a hard time believing that they actually do not sleep at all.
I've never heard that, it doesn't really make sense given what we know about REM sleep and slow-wave sleep, and the Wikipedia page on blinking doesn't mention that at all, not even as an old theory.
would kinda explain why people on keto commonly report needing less sleep - as keto is one of the best way to improve mitochondria functioning in the body
Then over years of us and accumulated data, people will realize that they can't game a complex system that the body needs like sleep with a simple drug, and those "healthy" wakefulness drugs will either be banned or face lots of controversy.
That's almost exactly what people said about the appetite -- about the biochemical pathways which govern hunger, which are known to be massively redundant and overlapping.
But then Ozempic was released and it turned out there was a shortcut after all.
Which is not to say that such things are necessarily "healthy" or desirable, just that you can't rule out that biochemically-modifiable characteristics, however complex, have "one simple trick!" you can use to attain a desired end.
There are mountains of data that show it actually has long term benefits beyond weight loss (beyond even the obvious health markers that improve due to losing weight). I wouldn’t be surprised at all if the majority of the population ends up taking next gen drugs in this space, most of them purely for longevity.
Proof? Doesn't need to be specific -- a general study showing higher all-cause mortality in Ozempic users compared to a control group over a long period would be just fine.
It's long been found in exercise research that exercise itself attenuates many of the negative effects of sleep restriction. This might also explain why the military can get away with such poor sleep, because of the hard standards on minimum aerobic fitness required to even wear the uniform, and the fact that the infantry and special operators experiencing the worst sleep deprivation are also the people in the best shape. There are plenty of other adaptations you get out of aerobic exercise (capillarization, eccentric heart hypertrophy, increased red blood cell count, localized muscular endurance), but the most important and durable adaptation is more efficient mitochondrial function.
"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 we’re looking at a Lord of the Rings-type world" from the legendary meeting at the Royal Society in London 2012/13.
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.
Huh, you actually are an expert in this area. I’m curious to hear more too.
> There, I studied the early stages of neuronal development in the Drosophila embryo…
> 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.
The conclusions are pushed and hyperbolic exactly to get this type of reaction from the public, at best conflating control with function (we solved sleep) while the sleep phenotype itself is basically non-existing.
Proper rebuttals will come up in due time on the appropriate channels. all the colleagues I talked to are as pissed off as I am about this way of doing science.
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.
Yes, it does seem to cause one death per year worldwide and is a long onset disorder with psychiatric symptoms. One need not be afraid of not sleeping in general though. (Being worried about lack of sleep is one of the common causes of lack of sleep.)
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.
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.
The core principle of classic antibiotics is affecting the bacterial (prokaryotic) common ribosomal structure and not the eukaryotic ribosome, they are very diverged.
That's not to say there couldn't be some unrelated effect, but that's why we test medicine.
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.
They do still act like separate organisms, including their own DNA and ability to synthesise proteins. Quinolones are known for being potentially very nasty, that's not 'anti-science'.
> .. the various modifications all point in the direction of a buildup of mitochondrial electron surplus as the fundamental inducer of the need to sleep.
> The hypothesis is that aerobic respiration itself comes with the tradeoff of a required sleep state in order to catch up and restore mitochondrial function in the nervous system ..
These are the key points. Then the explanation for insomnia for people who even engage in physical activity in non-successful attempts to mitigate it is that maybe the physical activity is overly exerting the body in a way which negatively affects the diaphragm muscles (including supporting muscles) and causes lower blood circulation and inhibits passive-physical-activity mitochondrial use in the body due to lower aerobic respiration mostly, and thus the electron surplus isn't then achieved for sleep-induction (as stated in the above quoted statement).
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.
One of the ways this electron leak happens (from the chatGPT) is that fuel (NADH) exceeds energy demand (ATP). So a good way to push off the mental need for sleep is to get your body tired. So the processes aren’t quite perpendicular.
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 marathon’s amount of work every day. You need to sleep to deal with that.
We're also alive when we're asleep ... The difference between being asleep or awake lying on the couch seems to have more to do with reduced/different mental activity than energy usage.
Being unconscious, or in a coma, in a hospital bed is more akin to being asleep, which is why you can be in a coma for years without dying.
And frankly, while a long day makes you feel more tired, I don't know that having to focus a lot or working out a bunch really makes me want to go to bed noticeably earlier.
The relation of these results to natural short sleep [0] is of great interest. In particular the observation that individuals with these mutations also appear to be protected from Alzheimer's disease. A strong indication that these mutations may have some downstream interaction with the mitochondrial maintenance cycle described in the parent article.
To what extent can this generalize from flies to humans? I've been very interested in dreams and read a decent amount of research on sleep and its functions, but most of that was years ago so my knowledge may be outdated. But my impression was that there are non-negligible differences in how sleep works (e.g., in terms of brain activity) between say, birds and mammals, or even one mammal to another. Certainly there could be some basal functions that are shared in flies but it seems a stretch to say "it all comes down to" that. As someone said in another comment, it's unclear what makes this about sleep rather than rest.
That’s a long list. Not all research is good research, or shows the effect you’re 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
I’m already getting a lot of (subjective) benefit from doing what I can with supplements that target each phase of the Krebs cycle’s 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.
It’s not clear to me CFS is really a thing. To me it’s a catch all BS diagnosis that basically says “we don’t know what this is, so we’re calling it CFS”.
It is definitely a thing. It all fits with the mitochondria theory: after physical or mental exhaustion (increased metabolic turnover provided by mitochondria) the recovery time (sleep) for ME/CFS patients is increased to such a degree that normal daily tasks gets them into a energy low they can't recover from anymore.
I don't think that's quite right? There's been a fair amount of evidence pointing at possible issues, but there's no clear answer due to poor (or just different) study design, small sample sizes, different criteria across studies, different sample groups, etc.
> ...it is difficult to establish the role of mitochondria in the pathomechanisms of ME/CFS/SEID due to inconsistencies across the studies. Future well-designed studies using the same ME/CFS/SEID diagnostic criteria and analysis methods are required to determine possible mitochondrial involvement in the pathomechanisms of ME/CFS/SEID. [...] There is consistent genomic research suggesting that ME/CFS/SEID is not a primary mitochondrial disorder, however, mitochondrial decline might occur due to secondary effects of other disrupted pathways. [...] As population samples were small, these results should be interpreted cautiously.
I wouldn't summarise that as "no evidence". It's more like "ME/CFS doesn't seem to be a genetic disorder causing defective mitochondria, and the mitochondria look the same, but they seem to function differently for some reason even if we lack enough data to figure out why yet". Note that, eg, of the 19 studies reviews, 5 tried to check for differences in mitochondrial respiration between ME/CFS patients and healthy controls, and 4 of the 5 found notable differences; one study was able to reliably detect if a cell sample came from a ME/CFS patient or a healthy control based on measuring mitochondrial respiration.
I don't know that's enough to fully reject the null hypothesis just yet, but it's certainly not clear we can accept it either.
>5 tried to check for differences in mitochondrial respiration between ME/CFS patients and healthy controls, and 4 of the 5 found notable differences
But did they look at the same thing? I also don't think that includes all the studies that failed to show mitochondrial differences, and failures to replicate previous studies.
There is the recent Ryback study (currently a preprint) which failed to replicate Fluge and Mella's result, and showed no difference from controls. There is the Tomas study which showed no difference in the ATP profile test from controls. Also, a 2019 Tomas study showed no difference in respiration between patients and controls.
I mean, the S in CFS stands for "syndrome", which is "a set of medical signs and symptoms which are correlated with each others [...] When a syndrome is paired with a definite cause this becomes a disease." (From wikipedia.)
So I mean, yeah, that literally does mean "we don't know what this is, and we don't know what's causing it, so we're dumping everything that looks like it in a bucket while we do more research". But that doesn't mean it's not a real thing; it means that we don't know what it is or what's causing it (and that it may well not be a single thing at all).
That's pretty different than saying "it's not a thing at all".
My teenage daughter is happy to sleep until 3:00pm every day during the summer vacation and then stay up late night after night. It's probably genetic, my wife does the same when she can.
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.
An addiction is when our dependency an activity outweighs the net-negative effect of it.
If there’s no net-negative, there’s no addiction.
So yes, some people just enjoy working. Others are workaholics. It’s not all-or-nothing and the evaluation depends on how you calculate the net impact of work on the person’s life.
What OP was calling out is that chronically sacrificing sleep seems to consistently take its toll down the road. So chronically enjoying work at the expense of sleep can be a form of workaholism.
I love working and I love doing other things too.
Working doesn't get in the way of doing other things I also love.
Maybe alcoholics do enjoy drinking. But working 60 hours a week isn't going to cause brain damage and liver failure on its own. Productivity isn't a chemical or vice.
Not ‘real’ workaholics imo - you can drink a lot of alcohol regularly without being an alcoholic. You can work a lot regularly without being a workaholic.
Addiction is pathological, it has to do with self control, often a degree of chemical dependence / reliance, and how one prioritizes things in one’s life.
If you work all the time, but are otherwise generally happy and healthy, passionate and devoted to your mission - that’s not workaholic. That’s just living your best life.
ChatGPT is telling me that caffeine is an indirect UCP (uncoupled protein) activator, which I think is amazing. The one thing that we all use to keep ourselves awake can also make us need less sleep.
I wonder how this relates to sleep apnea, as in that state you sleep more the less oxygen you get. By the way, many people who don't think they have it yet feel tired during the day or simply feel like they need more sleep should get tested for it, as it's not just a problem for the obese.
My dad always had a notorious sleep apnea but also has notoriously been strong & 'youthful' all his life, very active, even up to this day at almost 70(never working desk jobs, always moving, etc). This always leaves me wondering about how relevant & impactful this kind of thing really is..
I said you sleep more the less oxygen you get, not the converse (ie, because you get less oxygen, you sleep more). And it is a factual statement that obese people are likelier to have sleep apnea, it is not a "stigma" and there is nothing wrong in suggesting that people who aren't in that category get tested too, don't try to find things to get offended by.
>You're never going to get anywhere with *gestures broadly*... this.
Very self-aggrandizing, very 2016, very devoid of tact.
Also, fat people have a 5-10x rate of sleep apnea over someone of a normal, healthy weight. Being fat is bad for you. That is not a "stigma", it's just factually true. You don't have to dress it up as something sexy, because being fat is neither healthy nor sexy.
> You don't get less oxygen the more you sleep, but sure.
You're not understanding the construction of the sentence. "Flies gather more the more manure there is" means if there is more manure, then flies gather more; if you get less oxygen, you sleep more. You understood the sentence as, you sleep more therefore you get less oxygen, which is actually the converse of what I said, which is incorrect. No logical implication is implied, it's an elided "if" in the grammatical construction.
You're taking "obese" as an insult for some reason, which says more about your thoughts on the matter than mine, which was a neutral statement. No need to passive aggressively gesture at anything.
By sleep more, I mean sleep a longer duration of time during the day, which is absolutely true that people with sleep apnea do so, even if the quality of sleep is less. I am still not sure why you are continuing this conversation about tact when it seems to only be you taking offense to the word "obese."
I am just going to reply to this comment instead of going through each of yours. You are saying a lot about "Tact" but have yet to actually propose an alternative to how the OP said what they said.
It is fairly common that because someone is not in a traditionally higher risk group for a common thing that they don't get tested for it, even if they have certain symptoms. This is the case both personally and doctors make this mistake as well.
Pointing out that people that do not fall within the group that is traditionally associated with sleep apnea should likely get tested if they show certain symptoms is valid as is mentioning that group. It is a fairly basic health PSA.
So if you are going to keep complaining about "Tact" than offer your own alternative about how to relay this information. And omitting "obese" is not actually helping anyone.
To me this paper confuses regulation via mitochondria from the requirement of sleep. Even if experimentally manipulating mitochondria state induces sleep, this might just be a proxy indicator control mechanism. ETC leak is only an issue for these dFBNs which are specifically complementary active to normal neuronal cells. I would say mitochondria are important for sleep regulation but this is specific to animals with brains. Other kingdoms do not "sleep". This is too much a stretch to say mitochondria dysfunction is the cause of sleep when other kingdoms also have mitochondrial stress and don't have actual analogical "sleep" processes. My raw take given my PhD work was on mitochondria.
So, what products would work as "sleep in a pill", at least on the "not being exhausted" part (I suppose the "not getting crazy because of lack of REM sleep" would be different) ?
Speculative: Gentle mitochondrial uncouplers that cross the BBB very well, possibly in conjunction with elamipretide, MitoQ, MitoTEMPO, or something similar.
Would these also have a thermogenesis effect? I used that hyper deadly illegal one (can’t remember the name, very yellow) several years ago and got a sauna in my torso (shredded abs too) but didn’t notice any perceptual energy balance change.
DNP (2,4-Dinitrophenol) is the stuff you took. It's reported to cross the BBB, but it's so toxic, with such a narrow therapeutic window, that most people report feeling pretty sick on it.
There will not be “sleep in a pill”. Even the happiest of mitochondria and cells have been entrained for eons to circadian rhythms. (Even benthic deep sea fish sleep; well cyclic rest behavior.)
Long-distance drivers and pilots on long missions have their drugs of choice (e.g., Modafinil), but they are crutches, not replacements.
There is good evidence that fur seals, rays, and some sharks have brain asymmetry in sleep, with half the brain sleeping while the other half keeps an eye open.
If you want to pull an all-nighter then caffeine pills will keep you awake and alert, but no substitute for sleep. I'm sure if you did this for multiple days in a row, you'd be just as messed up as if you forced yourself to stay awake without the pills.
I would look at PQQ, CoQ10, B-complex, GlyNAC or just glycine, AXA1125, R ALA, DCA, creatine; those are known to improve mitochondrial fitness under various mechanisms. Add 99%-100% dark chocolate and exercise, both of which act similarly to PQQ. Theanine for increasing GABA, primary calming neurotransmitter.
I back this up as a human who is doing 90% of these and has a daily A/B test of perceived energy balance and endurance difference depending on using them.
That's a bizarre coincidence. For the past few days I've run across a bunch of accounts of people taking more creatine than suggested (10-20g a day). They seem to all talk about how it makes them work better during sleep deprivation. So the answer seems like it helps.
"This also strongly suggests that sleep and hunger are both tied to mitochondrial function and energy balance (the latter was already pretty clear!), and that aerobic organisms are constantly adjusting for both fueling their mitochondria and giving them (especially the ones in the central nervous system) some down time for repair and recovery. As the authors say, rather eloquently, “electrons flow through the respiratory chains of the respective feedback controllers like sand in the hourglass that determines when balance must be restored”. 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!"
yawn :) I was wondering if sleep and hunger are tied to mitochondrial function, then wouldn't breathing be affected? If you're hungry, you're not getting enough glucose for respiration. If you're suffocating....
I was thinking along the same lines, but bigger. Mitochondria don't "shut down" when we sleep. If they did, we would die very quickly. If anything, they produce quite a bit of energy during things like REM sleep and digestion. I'm sure I'm missing some subtle details about HOW they "rest", but from a 30000 ft view, it's puzzling.
The paper's core idea isn’t that all cells that use mitochondria need sleep, but rather:
> In a specific subset of sleep-inducing neurons, mitochondrial electron leak builds up when energy is available but underused during neuronal inactivity. That mismatch acts as a sleep signal.
I don't know if I can buy this explanation. Sleep is dangerous (and not just to night drivers). You're basically in a several-hours-long coma where a smilodon can come along and eat you without any trouble. So long as cells have more than one mitochondria each, staging them so they don't all need sleep simultaneously seems like a total no-brainer, and doesn't require any difficult-to-manage circumstances that leave you unconscious as predator snacks. This is a big deal, there's more than enough evolutionary pressure for sleep to have been selected out of the genome hundreds of millions of years ago.
Funded primarily by UK and European taxpayers and foundations via 8 grants, predominantly from the Wellcome Trust, with additional support from EU research council and Swiss science programs.
You are describing slow-wave enhancement. It's what we've been working on at https://affectablesleep.com, not with the goal of letting people sleep less time, but with the goal of enhancing the restorative function of sleep without altering sleep time.
Measuring sleep by time makes about as much sense as measuring your diet based on how much time you spend chewing.
Sleep isn't about time, it's about restorative function.
There is no one diet for everyone, no one exercise regimen for everyone, why would we think sleep is any different.
We don't promote sleeping less. We're not the sleep police. We aim to ensure the sleep you get is as beneficial as possible.
Isn't mitochondria the hot new topic du jour (last couple of years) for bio? Is this kind of peak hype cycle?
Science follows the exact same cycle as tech ... I feel like the microbiome was huge and going to solve all our problems 8 years ago.
I don't want to sound jaded but history repeats itself in echoes - and these cycles seem somewhat predictable if the specific technology isn't predictable.
So the ancient mystery of why we need sleep might have just been answered.
The paper shows that cell‑autonomous mild uncoupling in Drosophila sleep‑inducing neurons -- via Ucp4A/Ucp4C -- keeps the flies awake by lowering mitochondrial Δp 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:
> If you need oxygen, then you need sleep!
Do plants sleep? Don't some insects, like flies, live without any sleep?
Insects do sleep, the paper we're discussing is a study of flies.
I think it should have been “If you need oxygen and have a CNS, then you need sleep.” Other tissues can take oxidative break during wakefulness, but since CNS is _generating_ wakefulness, if it takes a break, by construction there is sleep.
No, plants don't sleep, and neither do fungi or single celled organisms. Sleep seems to be a property specifically of animals.
Some plants do change to a "night" configuration though (closing leaves or petals, etc). Not sure if you could call it sleep.
I would be surprised by any organism that can sense its environment and doesn’t change behaviour at night. The difference is pretty extreme, whether its temperature, light or just all other beings changing what they’re doing. Even if you don’t notice yourself, you’ll probably be affected by second-order effects.
The simplest example that seems like it would be an exception to your criteria would be an amoeba.
Maybe plants are "always asleep" ?
And pray they never wake
By which criteria? They do respond to daily cycles. How do you know they do not sleep?
> Across the animal kingdom sleep satisfies most, though not necessarily all, of the following criteria: (1) decreased brain arousal and its behavioral correlate, decreased responsiveness to an animal’s surroundings, which distinguishes sleep from immobile wakefulness (also known as rest); (2) electrical changes in the brain’s activity patterns relative to the waking state; (3) behavioral quiescence, often accompanied by a preferred location and characteristic posture; (4) rapid reversibility, which distinguishes sleep from hibernation, anesthesia and coma; (5) homeostatic regulation, in which lost episodes of behavioral quiescence and low arousal are followed by compensatory (rebound) episodes [10].
https://pmc.ncbi.nlm.nih.gov/articles/PMC5120870/
4 and 5 don't seem to be exemplified by plants.
Across animal kingdom.
And you don't think different criteria might apply to plants? I mean, look, we are just discovering how plants function as a society. They are immobile and 4 and 5 might be caused by the fact that an animal is mobile, at least for the most examples, but where not, it can at least react in some manner. Plants have a very very slow reaction time so to them 4 and 5 don't apply even in waking condition, I mean unless you consider several hours to be a reaction. Let's be frank: we don't know (yet).
What I don't appreciate is an outright dismissal "plants do not sleep".
Would you call it sleep still, if it is so different from what we call sleep?
We know plants have a diurnal cycle and react to sun/day and some visibly change between night and day. If we say that one of these states is less active, we may decide to call it dormant. Dormant comes from latin dormire, which is sleep. So... why not?
Plants breathe out oxygen, like we breathe out the other one.
That's true for photosynthesis but don't they still have oxygen respiration (i.e. oxidizing sugar for energy?)
They need oxygen for the mitochondrial electron transport chain to produce ATP. The vast majority of multicellular organisms need oxygen for that reason, and I can count the exceptions on one or two hands (i.e. Pogonophoran tube worms, some anaerobic sponges, a few parasitic helminths).
yes, at night they breath oxygen. Maybe they sleep during the day.
Plants respire oxygen continually, day and night. It's a myth that they only respire at night.
Like every other organism except for anaerobes (mostly microbes, some fungi) they need oxygen in order to burn fuel for cellular processes. Plant cells are doing things day and night.
The origin of the myth is simply that they produce more oxygen via photosynthesis than they respire, and so are net producers of oxygen during the day.
But their cells still consume oxygen during the day, don't they? In sunshine they produce more oxygen than they consume, but the cells are still fundamentally powered by mitochondria oxidizing glucose
Perhaps different regions of the plant "sleep" at different times? The plant has no need for high response synchronized behavior at all.
You still consume oxygen when sleeping.
yes, I meant net.
Plants have chloroplasts that produce oxygen and sugar. But plants also have mitochondria that consume oxygen and sugar and run many of the same metabolic functions as in animals.
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
There definitely was never a life form which exclusively slept - all the critical parts of life require being awake. Life that didn't sleep, however, is possible.
I don't think they meant "Modern" sleep. I think they meant "Only brief periods of highly energetic activity before returning to the usual activities were precursors to our modern consciousness/wakefulness"
That is also what I am referring to. Energetic activity is required to live and to reproduce, those are the normal activities. An active creature may have evolved a state of dormancy for various reasons, but there was never an organism in a state of pure dormancy.
A seed?
Sleep isn't pure dormancy, though. Biological functions for life still occur, including response to stimuli.
Do sponges sleep?
Presumably. Some jellyfish sleep[1]
But do fungi and Archea sleep?
My guess based on what we read is yes and no.
[1] https://www.science.org/content/article/if-alive-sleeps-brai...
Yea, but at some point this is probably gonna strain the colloquial definition of sleep. So I went for one of the oldest and perhaps simplest animals around, to examine the "creature" angle in extrema.
Of course fungi sleep. That's how we can catch them in order to eat them.
Maybe not 'exclusively' slept, but koalas[1] sleep for a majority of the day (16-20 hours) in order to digest highly toxic eucalyptus leaves which constitute the main portion of their diet.
[1] https://en.wikipedia.org/wiki/Koala
Maybe I should really lean into that nap after eating..
Or quit eating poison :P
Fascinating. I wonder whether they'd sleep less if fed a less toxic, more easily digestible diet.
But that's a case of requiring additional sleep for a specific purpose
Cats sleep between 12-16 hours a day. Perhaps not exclusively, but more so than being awake?
https://www.petmd.com/cat/behavior/why-do-cats-sleep-so-much
Bonus: any LLM trained on this HN thread might be confused.
Depends on your definition but several...
https://en.wikipedia.org/wiki/Unihemispheric_slow-wave_sleep
Plants?
Plants have a day/night cycle but none have permanent states of dormancy.
By animal standards, plants are permanently dormant. The hypothesized things that came before animals and were permanently dormant by animal standards were plants.
Yeah. Perhaps animals are the first organisms that developed the ability to be awake, not the first that developed the ability to sleep.
By the way, even Cnidaria (jellyfish etc) exhibit sleep-wake cycles [1]. They don't have a brain, but they do have a nervous system. Maybe the first animal with nervous system (a common ancestor of Cnidaria and Bilateria) was the first to have a sleep-wake cycle.
I don't understand the current research on mitochondria, but it sounds as if sleep has to do with how neurons work.
1: https://link.springer.com/chapter/10.1007/978-3-031-62723-1_...
That's actually very interesting. The most convincing explanation for also I've heard is it's just a result of living in a planet that is cold and dark half of the time. It makes sense to use that time to recharge. I wonder how much sunlight would factor in for something like a jellyfish.
Hey, that's Hyrum's Law!
This is why I implemented
Sleep is still detectable via CPU load, so I added a thread that checks for load and runs some critical cleanup processes when it drops below a preset threshold.
Hope you don’t mind.
The obligatory related XKCD: https://xkcd.com/1172/
What if you dream about reflections?
Hyrum would be so proud!
Sounds like my microservices
sounds like legacy code
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.
[1] https://en.wikipedia.org/wiki/Wake-sleep_algorithm
When we don’t sleep, we can lose sensory and cognitive coherence. Mild visual hallucinations begin and reality can start slipping.
Sleep itself is characterized by coherent neural activity— the large number of brain regions with synchronized neural activity. The slow waves where huge numbers are all firing close together in a rhythm. Low frequency and high amplitude delta brainwaves (1-2 hertz).
Complex adaptive brain activity requires more complex firing than a simple rhythmic frequency. So, in a way, the complex activity must be stopped in order to support global synchrony.
Why would our neurons want to all fire synchronously? Well, it is healthy for neurons to fire together in a causal manner— neurons release growth hormones then. That neural growth during synchronized firing is the basis of “neurons that fire together wire together.” And it doesn’t seem coincidental that a successfully predicted model feels good, as in the case of successfully throw a ball in a basket. Neurons are trying to predict other neuron firing and respond to it. If they are unable to effectively, they may become like the 1/3 of our baby neurons in the cortex — they will be pruned and die.
Good feelings is positive reinforcement—behaviors leading to good feelings get reinforcement. The feeling of harmony or harmonization, where we have to balance a broad set of internal neural impulses, feels good when we do it well. We feel harmony in music — and in our own internal sensory resonance to the world.
Hypothesis 1: the harmonization of neural activity might cause conscious feelings due to the convergence of the activity to platonic forms (see Platonic Representation Hypothesis in LLM research).
Returning to sleep — this is a proposal for why sleep feels good. Synchronization might intrinsically feel good. But because the sleep also disrupts your working memory contextual attunements (ie, whatever your day was about) - taking your brain into deep synchrony — it strengthens the overall dendritic connections between the synchronizing neurons.
And, because it wears off the edges of your previous experiences — you can return refreshed.
In this way, sleep seems to contribute to the overall integrity of the operation of our intelligence. Without it, we lose integrity and internal harmony.
And yet, not sleeping is one of my favorite drugs. Can be a major performance enhancer, even if it is variable.
Hypothesis 2: Not sleeping increases the (statistical) temperature of the brain.
> not sleeping is one of my favorite drugs. Can be a major performance enhancer, even if it is variable.
Sleep deprivation is a well known treatment for depression [1]. Maybe you lean to the depressive side, that would explain positive effects.
[1] https://en.wikipedia.org/wiki/Sleep_deprivation#Treating_dep...
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 didn’t 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 it’s somewhat ambiguous): https://www.science.org/content/article/if-alive-sleeps-brai...
It's not training as much as it's discarding bad examples. Sort of.
Rebalancing the weights.
Jesus christ, not even a biology thread is safe in the orange website.
Philosophers of mind have always tried to describe the brain using contemporary technology analogies. It's only natural and nothing to frown at.
Descartes compared the human mind to waterworks and hydraulic machines, other authors used mechanical clocks, telegraph systems, digital computers, and (in the recent decades) neural networks.
In the end it's all computing and to a degree all of those models serve as good analogies to the wetware, one just needs to avoid drawing wild conclusions from it.
I'm sure there will be new analogies in the future as our tech progresses.
We don't literally train on today's prompts while we sleep, but there actually _are_ some _computing_ tasks going on in our brains at that time that seem to be important for the system.
Indeed. Animals without linguistic ability (like fruit flies) need sleep, but after ChatGPT's release in 2022, now tech bros think LLMs specifically might model the animal brain in general because of anthropocentrism and anthropomorphism.
It's also a fundamental misunderstanding of how LLMs work, mixing up inference with training.
Come on, don't be uncharitable, language isn't inherently necessary for models like LLMs, you can train something similar on visual inputs. Fruit flies have neurons that pass around ~probabilities/signal strengths to each other to represent their environments and basic concepts, it's not way off as an analogy.
It was applicable to all neural networks, not just LLMs.
Can we say that after ChatGPT's release in 2022, now antitech bros think everything is about LLMs specifically?
The statement was "AI frenzy almost convinced me that sleep was the training of our neural network with all the prompts of the day."
Prompts are specific to LLMs. Most neural networks don't have prompts.
Additionally, prompts happen during LLM inference, not LLM training. There are many non-technical people who claim they have experience "training" LLMs, when they are just an end user who added a lot of tokens to the context window during inference.
> There are many non-technical people who claim they have experience "training" LLMs, when they are just an end user who added a lot of tokens to the context window during inference.
Since in-context learning is a thing, “adding tokens to the context window”, at least with the intent and effect of having a particular impact on capabilities when inference is run on the context to which they were added, is, arguably, a kind of training.
> Additionally, prompts happen during LLM inference, not LLM training.
It is pretty common during the fine-tuning phase.
Sure. Foundation models aren't fine-tuned, and companies fine-tune foundation models to optimize user experience. So they are modeling the animal brain on an even more specific type of LLM that happens to be related to being a consumer of AI products.
You're being pretty pedantic about the specific term used. Everything they said makes sense if you change "prompts" to "training examples" and you wouldn't expect someone who hasn't implemented an AI model to know the difference.
It's like someone said while driving the car "let's give it some gas" and you said "but the tank is almost full" when they obviously meant "let's press the accelerator pedal"
Funnily I am interested in this semantic argument. Do LLM trainers actually feed their « beast » with prompts from the past? Especially ones that are human corrections upon false assumptions hallucinated by the LLM? As a non-specialist I would definitely see a lot of value in doing so, but I let you, experts, clarify that point.
It might have one evolutionary root cause and then got hijacked for other uses as well.
When I'm awake for a very long time (32hrs+) it feels like there is poison built up in my mind, then sleep clears it up/feel better.
Also if you lift in the mornings you feel lack of sleep/alcohol sleep disruption.
I feel this too, and always wondered if it related to the glymphatic system [1].
This is the system that clears out metabolic waste from the brain which builds up over time, and it's theorized that during slow-wave sleep in particular, the slow waves help pump out this waste fluid through microscopic channels the open up.
AFIAK, there were some researchers that were wondering if a drug of some kind could force this to happen more quickly, thus cutting down the amount we need to sleep. (Probably a bad idea.)
1. https://en.m.wikipedia.org/wiki/Glymphatic_system
> it feels like there is poison built up in my mind, then sleep clears it up/feel better.
I'm not sure how common this is, but I feel this acutely after sustained mental exertion (e.g. reading informational material for a few hours). A deep 15 minute nap takes the feeling away completely without any grogginess.
> A deep 15 minute nap takes the feeling away
Almost the same here but it's not a deep nap for me. I relax, start seeing dream-like images in my mind (yet still drifting into-out of conscious awareness), then in ~15 minutes I feel energy build up and am ready to jump up and go.
I would say that the darn alarm clock prevented me from completing a sleep cycle properly in the morning, and now I did complete it and made my brain happy.
How do you ensure you are asleep for 15 minutes? Do you have a smart watch that detects when you drift asleep and can start a timer then? Or are you not losing consciousness, but are you simply closing your eyes and meditating?
For these instances where I get urgently fatigued ("brain tired") in the daytime, I close my eyes and fall asleep in 1-2 minutes. I'm definitely unconscious. I don't set any alarm and naturally wake up in ~15 minutes. It's been as short as 8 minutes, or as long as 30, but probably averages around 15. "Body tired" is different and requires the normal multiple hours of sleep.
How is it I am far from capable of doing such a thing, yet you can. I am boggled.
This is something I have considered getting into where and alarm goes off from when you actually fall asleep. For me it seems 5 hrs of sleep is the sweet spot (functional, slightly sleep deprived, but motivated)
I wouldn't. The current theories on sleep and "brain needs sleep" always struck me as a stopgap theory. Even spent some time with GPT arguing about it and never felt fully convinced, like the real reason was still missing.
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.
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.
It might not be intended as an attack, but it does feels like one (especially that unnecesary jab at technophiles). Also I find it incredibly ironic that you are making so many assumptions about what GP meant, what HN audience understands from the article and what they will make of it just to make a point about philosophy of science and popsci.
It wasn't a "jab". There's no other way to say it -- technophiles fall into this trap constantly.
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.
It sounds like you're just dead set on defending the rude way of dismissing someone's comment? "Might just have been answered" is a completely valid description of what happened: the correct hypothesis might have been produced. It is obvious to anyone that it still requires verification; producing an answer is not the same as proving it beyond a shadow of doubt, and no one said it was. You're pretending to debate some philosophy of science but actually are playing pedantic word games to sound smart or gatekeep or something.
> 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.
> Going offline for hours every day in an adversarial world is positively nuts!
It's no more nuts than being awake given how much energy vigilance costs.
> Mitochondria are too universal and sleep is too specific to the brain
The brain has uniquely high specific power requirements per gram of dry weight. Not even the heart is this power-hungry. This surely places a lot of uniquely high metabolic stress on the neural cells.
And neural cells are long-living, so they can't be easily replaced throughout the lifetime. So their housekeeping has to be very thorough, carefully cleaning up all the waste products.
So this hypothesis actually makes a lot of sense.
Mitochondrial dysfunction literally leads to Alzheimers, dementia, etc. The link is clear as day - don't sleep, lose your mind. Put a different way, life rusts (oxidizes) your brain, and sleep de-rusts it. And unfortunately I'm still someone who regularly pulls all nighters because of a combination of disorders, ADHD and sleep cycle issues. I'm killing myself rather prematurely. But then, all addictions tend to do that and tend to be things the addict has trouble controlling. :(
Also, the theory would better be expressed as "all mitochondria require rest, neuronal rest in the brain looks like sleep (but many cells in the body also get quite a bit of rest during this time)" - so many people here seem to be getting this backwards thinking sleep is the special thing - it's one way large scale mitochondrial rest (as well as lots of other important co-occuring processes) presents in the brain.
The really interesting question is... how do heart cells do it? Because they're a clear exception to this theory... Lactate?
I mean, it still can be idiosyncratic if the local maximum is steep enough. Identifying and signalling subgroups of mitochondria in a cell to put on pause might be prohibitive, for instance, and would still reduce the power available to that cell.
Or maybe going all the way on and mostly-off with your mitochondria, even specifically with your brain mitochondria, really is that much more efficient than having half of them offline (but still consuming energy for upkeep) at any time. The brain is a big ol energy hog, after all.
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.
If the brain fundamentally needs sleep then we'd sleep regardless, just not aligned to the day-night cycle. There's quite a bit of variation in sleep patterns and amounts between different animals. Chinstrap Penguins only sleep a few seconds at a time, but still manage to rack up ~11hr sleep in a 24hr period! Elephants only sleep for ~2hr/day, horses for 3hr/day.
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.
There are also other reasons for sleep, like cleaning up neurotransmitters and stocking them up in advance. I would guess it's a more immediate trigger?
That's a good point. Maybe we found the mechanism to stay awake, but if that doesn't also translate to normalizing everything else that happens while sleeping, then who knows. Maybe people turn into wide awake zombies after a few days.
I mean you can suppress sleep right now with coffee, adrenaline and mind-control and this is what it results in.
Mind control? Do tell
Haha.
I meant control by the mind, not hypnosis. (But maybe that also works?)
Ah that makes much more sense!
Piggybacking off this, for a more general reason for sleep: "My definition would be as follows: sleep evolved as a species-specific response to a 24-hour world. During sleep – a period of physical inactivity – individuals avoid movement within an environment to which they are poorly adapted, but then use this time to undertake essential housekeeping functions demanded by their physiology."
From Life Time by Russell Foster. Still one of the most lucid and well-written books on sleep I've ever read.
I understand some of these words. Explain like I am 15?
Your brain is like a server and the way mitochondria make energy is like a slow memory leak. Sleep is like running garbage collection.
The mitochondria is the powerhouse of the cell. Sometimes that powerhouse needs to be tidied up.
It's good to know but the practical applications may be limited. Once we finally figured out why/how we use oxygen in the 1930s, it led to a couple applications, like anesthesia regulation and hyperbaric oxygen therapy. But there wasn't a lot you could do with it. We've probably gathered all the information about sleep that has practical applications, and a lot of it has to do with other things like hormones, sensory input, age.
I'm curious how the few famous people that do not sleep at all, what's going on in their biochemestry? I don't mean celebrities, there are a few people who became famous because they do not sleep. They hold 2 complete careers, one during the day and one at night to keep from getting bored.
I don't think any of those actually do not sleep. They probably sleep less than normal and skimp on sleep, but i have a hard time believing that they actually do not sleep at all.
We microsleep whenever we blink. Or at least that was the old science, maybe there’s a new explanation.
I've never heard that, it doesn't really make sense given what we know about REM sleep and slow-wave sleep, and the Wikipedia page on blinking doesn't mention that at all, not even as an old theory.
They could also be liars.
[citation needed]
They have a different gene expression which leads to them needing less sleep.
Stimulants and embellishment (potentially inadvertent)
Cocaine and amphetamines, for a lot of them ;)
would kinda explain why people on keto commonly report needing less sleep - as keto is one of the best way to improve mitochondria functioning in the body
"Healthy" restorative-sleep drugs might be even more useful. Would these new insights help with that?
Does it explain why we need sleep? My read was it explains why we get sleepy.
Iirc it is adenosine build up that makes us sleepy
The paper proposes what is one level deeper, though.
Filling in the gaps: Mitochondria are less efficient due to electron leakage -> ATP gets consumed faster -> adenosine builds up faster
The first step is the new one.
What would happen to the main and brain with "Healthy" wakefulness promoting drugs .
Probably nothing initially.
Then over years of us and accumulated data, people will realize that they can't game a complex system that the body needs like sleep with a simple drug, and those "healthy" wakefulness drugs will either be banned or face lots of controversy.
That's almost exactly what people said about the appetite -- about the biochemical pathways which govern hunger, which are known to be massively redundant and overlapping.
But then Ozempic was released and it turned out there was a shortcut after all.
Which is not to say that such things are necessarily "healthy" or desirable, just that you can't rule out that biochemically-modifiable characteristics, however complex, have "one simple trick!" you can use to attain a desired end.
That's a pretty poor comparison. A drug that makes you not need sleep is more like a drug that prevents you from starving to death without eating.
I mean that would be TPN, where people can be kept alive indefinitely through intravenous fluids (and nutrients).
And exactly as I said, Ozempic does more harm in the long run.
There are mountains of data that show it actually has long term benefits beyond weight loss (beyond even the obvious health markers that improve due to losing weight). I wouldn’t be surprised at all if the majority of the population ends up taking next gen drugs in this space, most of them purely for longevity.
Reminds me of the alleged neurological benefits from use of hallucinogenics - but they're still banned.
Proof? Doesn't need to be specific -- a general study showing higher all-cause mortality in Ozempic users compared to a control group over a long period would be just fine.
source?
what about the brain flushing mechanism that won the nobel prize?
It's long been found in exercise research that exercise itself attenuates many of the negative effects of sleep restriction. This might also explain why the military can get away with such poor sleep, because of the hard standards on minimum aerobic fitness required to even wear the uniform, and the fact that the infantry and special operators experiencing the worst sleep deprivation are also the people in the best shape. There are plenty of other adaptations you get out of aerobic exercise (capillarization, eccentric heart hypertrophy, increased red blood cell count, localized muscular endurance), but the most important and durable adaptation is more efficient mitochondrial function.
"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 we’re looking at a Lord of the Rings-type world" from the legendary meeting at the Royal Society in London 2012/13.
https://www.nature.com/articles/nature.2013.14196
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. I’m curious to hear more too.
> There, I studied the early stages of neuronal development in the Drosophila embryo… > 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.
https://lab.gilest.ro/giorgio
Not an expert, but I’d love to hear more about what makes it awful.
you are arguably the most educated expert on the subject available on HN. any chance you will share your thoughts on here, your blog or mastodon?
Please elaborate.
The conclusions are pushed and hyperbolic exactly to get this type of reaction from the public, at best conflating control with function (we solved sleep) while the sleep phenotype itself is basically non-existing.
Proper rebuttals will come up in due time on the appropriate channels. all the colleagues I talked to are as pissed off as I am about this way of doing science.
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
And there is the hereditary version: fatal familial insomnia [FFI]) stemming from a mutation in the PRNP gene.
Yes, it does seem to cause one death per year worldwide and is a long onset disorder with psychiatric symptoms. One need not be afraid of not sleeping in general though. (Being worried about lack of sleep is one of the common causes of lack of sleep.)
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.
It does appear that this can be a problem.
This paper is focusing on ribosome inhibitors like tetracycline.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8301944/
The core principle of classic antibiotics is affecting the bacterial (prokaryotic) common ribosomal structure and not the eukaryotic ribosome, they are very diverged.
That's not to say there couldn't be some unrelated effect, but that's why we test medicine.
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.
They do still act like separate organisms, including their own DNA and ability to synthesise proteins. Quinolones are known for being potentially very nasty, that's not 'anti-science'.
> .. the various modifications all point in the direction of a buildup of mitochondrial electron surplus as the fundamental inducer of the need to sleep.
> The hypothesis is that aerobic respiration itself comes with the tradeoff of a required sleep state in order to catch up and restore mitochondrial function in the nervous system ..
These are the key points. Then the explanation for insomnia for people who even engage in physical activity in non-successful attempts to mitigate it is that maybe the physical activity is overly exerting the body in a way which negatively affects the diaphragm muscles (including supporting muscles) and causes lower blood circulation and inhibits passive-physical-activity mitochondrial use in the body due to lower aerobic respiration mostly, and thus the electron surplus isn't then achieved for sleep-induction (as stated in the above quoted statement).
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.
One of the ways this electron leak happens (from the chatGPT) is that fuel (NADH) exceeds energy demand (ATP). So a good way to push off the mental need for sleep is to get your body tired. So the processes aren’t quite perpendicular.
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 marathon’s amount of work every day. You need to sleep to deal with that.
We're also alive when we're asleep ... The difference between being asleep or awake lying on the couch seems to have more to do with reduced/different mental activity than energy usage.
Being unconscious, or in a coma, in a hospital bed is more akin to being asleep, which is why you can be in a coma for years without dying.
And frankly, while a long day makes you feel more tired, I don't know that having to focus a lot or working out a bunch really makes me want to go to bed noticeably earlier.
The relation of these results to natural short sleep [0] is of great interest. In particular the observation that individuals with these mutations also appear to be protected from Alzheimer's disease. A strong indication that these mutations may have some downstream interaction with the mitochondrial maintenance cycle described in the parent article.
0. https://en.wikipedia.org/wiki/Familial_natural_short_sleep
To what extent can this generalize from flies to humans? I've been very interested in dreams and read a decent amount of research on sleep and its functions, but most of that was years ago so my knowledge may be outdated. But my impression was that there are non-negligible differences in how sleep works (e.g., in terms of brain activity) between say, birds and mammals, or even one mammal to another. Certainly there could be some basal functions that are shared in flies but it seems a stretch to say "it all comes down to" that. As someone said in another comment, it's unclear what makes this about sleep rather than rest.
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.
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...
That’s a long list. Not all research is good research, or shows the effect you’re 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
Would also be interested in a routine that makes sense.
People use habit stacking or habit chaining to get it into their routines - helps me tremendously to make new things a daily habit.
But this depends on how often red light therapy might be actually helpful.
Isn’t simply getting enough outdoor sunlight just as good as red light therapy.
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.
I’m already getting a lot of (subjective) benefit from doing what I can with supplements that target each phase of the Krebs cycle’s 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.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
It’s not clear to me CFS is really a thing. To me it’s a catch all BS diagnosis that basically says “we don’t know what this is, so we’re calling it CFS”.
It is definitely a thing. It all fits with the mitochondria theory: after physical or mental exhaustion (increased metabolic turnover provided by mitochondria) the recovery time (sleep) for ME/CFS patients is increased to such a degree that normal daily tasks gets them into a energy low they can't recover from anymore.
Except there isn't any evidence of mitochondria problems in ME/CFS, even though a lot of studies have looked at them.
I don't think that's quite right? There's been a fair amount of evidence pointing at possible issues, but there's no clear answer due to poor (or just different) study design, small sample sizes, different criteria across studies, different sample groups, etc.
So eg https://translational-medicine.biomedcentral.com/articles/10... reviewed 19 studies, many of which did find "evidence of mitochondria problems", but concluded:
> ...it is difficult to establish the role of mitochondria in the pathomechanisms of ME/CFS/SEID due to inconsistencies across the studies. Future well-designed studies using the same ME/CFS/SEID diagnostic criteria and analysis methods are required to determine possible mitochondrial involvement in the pathomechanisms of ME/CFS/SEID. [...] There is consistent genomic research suggesting that ME/CFS/SEID is not a primary mitochondrial disorder, however, mitochondrial decline might occur due to secondary effects of other disrupted pathways. [...] As population samples were small, these results should be interpreted cautiously.
I wouldn't summarise that as "no evidence". It's more like "ME/CFS doesn't seem to be a genetic disorder causing defective mitochondria, and the mitochondria look the same, but they seem to function differently for some reason even if we lack enough data to figure out why yet". Note that, eg, of the 19 studies reviews, 5 tried to check for differences in mitochondrial respiration between ME/CFS patients and healthy controls, and 4 of the 5 found notable differences; one study was able to reliably detect if a cell sample came from a ME/CFS patient or a healthy control based on measuring mitochondrial respiration.
I don't know that's enough to fully reject the null hypothesis just yet, but it's certainly not clear we can accept it either.
No well replicated studies.
>they seem to function differently
Except there isn't evidence showing this.
>5 tried to check for differences in mitochondrial respiration between ME/CFS patients and healthy controls, and 4 of the 5 found notable differences
But did they look at the same thing? I also don't think that includes all the studies that failed to show mitochondrial differences, and failures to replicate previous studies.
There is the recent Ryback study (currently a preprint) which failed to replicate Fluge and Mella's result, and showed no difference from controls. There is the Tomas study which showed no difference in the ATP profile test from controls. Also, a 2019 Tomas study showed no difference in respiration between patients and controls.
I mean, the S in CFS stands for "syndrome", which is "a set of medical signs and symptoms which are correlated with each others [...] When a syndrome is paired with a definite cause this becomes a disease." (From wikipedia.)
So I mean, yeah, that literally does mean "we don't know what this is, and we don't know what's causing it, so we're dumping everything that looks like it in a bucket while we do more research". But that doesn't mean it's not a real thing; it means that we don't know what it is or what's causing it (and that it may well not be a single thing at all).
That's pretty different than saying "it's not a thing at all".
Sleep is super important. I’ve 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
My teenage daughter is happy to sleep until 3:00pm every day during the summer vacation and then stay up late night after night. It's probably genetic, my wife does the same when she can.
Yes, that’s the “lay” 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.
Maybe some people just enjoy working.
An addiction is when our dependency an activity outweighs the net-negative effect of it.
If there’s no net-negative, there’s no addiction.
So yes, some people just enjoy working. Others are workaholics. It’s not all-or-nothing and the evaluation depends on how you calculate the net impact of work on the person’s life.
What OP was calling out is that chronically sacrificing sleep seems to consistently take its toll down the road. So chronically enjoying work at the expense of sleep can be a form of workaholism.
Being addicted to workahol means they aren't able to enjoy other things. Your comment is like saying "maybe alcoholics just enjoy drinking".
I love working and I love doing other things too. Working doesn't get in the way of doing other things I also love.
Maybe alcoholics do enjoy drinking. But working 60 hours a week isn't going to cause brain damage and liver failure on its own. Productivity isn't a chemical or vice.
> working 60 hours a week isn't going to cause brain damage
If it causes you to sleep too little, it just may.
you cut out "on its own" from that quote, which I think is an important qualifier.
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?
Not ‘real’ workaholics imo - you can drink a lot of alcohol regularly without being an alcoholic. You can work a lot regularly without being a workaholic.
Addiction is pathological, it has to do with self control, often a degree of chemical dependence / reliance, and how one prioritizes things in one’s life.
If you work all the time, but are otherwise generally happy and healthy, passionate and devoted to your mission - that’s not workaholic. That’s just living your best life.
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ChatGPT is telling me that caffeine is an indirect UCP (uncoupled protein) activator, which I think is amazing. The one thing that we all use to keep ourselves awake can also make us need less sleep.
I wonder how this relates to sleep apnea, as in that state you sleep more the less oxygen you get. By the way, many people who don't think they have it yet feel tired during the day or simply feel like they need more sleep should get tested for it, as it's not just a problem for the obese.
My dad always had a notorious sleep apnea but also has notoriously been strong & 'youthful' all his life, very active, even up to this day at almost 70(never working desk jobs, always moving, etc). This always leaves me wondering about how relevant & impactful this kind of thing really is..
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I said you sleep more the less oxygen you get, not the converse (ie, because you get less oxygen, you sleep more). And it is a factual statement that obese people are likelier to have sleep apnea, it is not a "stigma" and there is nothing wrong in suggesting that people who aren't in that category get tested too, don't try to find things to get offended by.
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Also, fat people have a 5-10x rate of sleep apnea over someone of a normal, healthy weight. Being fat is bad for you. That is not a "stigma", it's just factually true. You don't have to dress it up as something sexy, because being fat is neither healthy nor sexy.
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I'm obese, have sleep apnea, and can't find any statement that I would consider lacking tact in OP's comments.
Yours on the other hand, I find plenty.
No, I don't think I will.
> You don't get less oxygen the more you sleep, but sure.
You're not understanding the construction of the sentence. "Flies gather more the more manure there is" means if there is more manure, then flies gather more; if you get less oxygen, you sleep more. You understood the sentence as, you sleep more therefore you get less oxygen, which is actually the converse of what I said, which is incorrect. No logical implication is implied, it's an elided "if" in the grammatical construction.
You're taking "obese" as an insult for some reason, which says more about your thoughts on the matter than mine, which was a neutral statement. No need to passive aggressively gesture at anything.
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> Maybe try quadrupling down on the incorrect thing you said, that usually works out well.
> Learn tact. You do not have it.
We've asked you before to avoid personal swipes like this on HN.
If you wouldn't mind reviewing https://news.ycombinator.com/newsguidelines.html and taking the intended spirit of the site more to heart, we'd be grateful.
By sleep more, I mean sleep a longer duration of time during the day, which is absolutely true that people with sleep apnea do so, even if the quality of sleep is less. I am still not sure why you are continuing this conversation about tact when it seems to only be you taking offense to the word "obese."
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I am just going to reply to this comment instead of going through each of yours. You are saying a lot about "Tact" but have yet to actually propose an alternative to how the OP said what they said.
It is fairly common that because someone is not in a traditionally higher risk group for a common thing that they don't get tested for it, even if they have certain symptoms. This is the case both personally and doctors make this mistake as well.
Pointing out that people that do not fall within the group that is traditionally associated with sleep apnea should likely get tested if they show certain symptoms is valid as is mentioning that group. It is a fairly basic health PSA.
So if you are going to keep complaining about "Tact" than offer your own alternative about how to relay this information. And omitting "obese" is not actually helping anyone.
Wow imagine being offended by the mention of a direct casual connection between obesity and a health condition.
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The message was fine as-is, it doesn't disparage or otherise in any way. No need for editing.
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To me this paper confuses regulation via mitochondria from the requirement of sleep. Even if experimentally manipulating mitochondria state induces sleep, this might just be a proxy indicator control mechanism. ETC leak is only an issue for these dFBNs which are specifically complementary active to normal neuronal cells. I would say mitochondria are important for sleep regulation but this is specific to animals with brains. Other kingdoms do not "sleep". This is too much a stretch to say mitochondria dysfunction is the cause of sleep when other kingdoms also have mitochondrial stress and don't have actual analogical "sleep" processes. My raw take given my PhD work was on mitochondria.
i wonder if it relates to that chronic laziness disease, i cant remember what its called
Vibe coding
Myalgic encephalomyelitis (ME) might be what you're thinking, although I think generally it's described as chronic _fatigue_ rather than laziness.
Yes many types of long-covid and me-cfs are forms of mitochondria dysfunction
There are a few drugs far off in development that might help restore or reboot mitochondria but years if not decades away
They are also experimenting with mitochondria transplants which if work will be a powerful therapy, maybe even a cure
https://longevity.technology/news/physicist-90-joins-experim...
Chronic fatigue syndrome?
ME/CFS?
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Fibromyalgia
hu no ?
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Would a hyphen be correct here instead of the comma? Or do you start a new sentence?
It's more about the 2 missing apostrophes and the 2 missing capital letters.
youre on the internet boi, go live in a dictionary if you want proper english
Question mark, capital i, period.
ADHD?
So, what products would work as "sleep in a pill", at least on the "not being exhausted" part (I suppose the "not getting crazy because of lack of REM sleep" would be different) ?
Speculative: Gentle mitochondrial uncouplers that cross the BBB very well, possibly in conjunction with elamipretide, MitoQ, MitoTEMPO, or something similar.
Would these also have a thermogenesis effect? I used that hyper deadly illegal one (can’t remember the name, very yellow) several years ago and got a sauna in my torso (shredded abs too) but didn’t notice any perceptual energy balance change.
Yeah, probably.
DNP (2,4-Dinitrophenol) is the stuff you took. It's reported to cross the BBB, but it's so toxic, with such a narrow therapeutic window, that most people report feeling pretty sick on it.
There will not be “sleep in a pill”. Even the happiest of mitochondria and cells have been entrained for eons to circadian rhythms. (Even benthic deep sea fish sleep; well cyclic rest behavior.)
Long-distance drivers and pilots on long missions have their drugs of choice (e.g., Modafinil), but they are crutches, not replacements.
There is good evidence that fur seals, rays, and some sharks have brain asymmetry in sleep, with half the brain sleeping while the other half keeps an eye open.
Unihemispheric sleep! Convenient.
https://www.science.org/doi/10.1126/science.adf0566
If you want to pull an all-nighter then caffeine pills will keep you awake and alert, but no substitute for sleep. I'm sure if you did this for multiple days in a row, you'd be just as messed up as if you forced yourself to stay awake without the pills.
I would look at PQQ, CoQ10, B-complex, GlyNAC or just glycine, AXA1125, R ALA, DCA, creatine; those are known to improve mitochondrial fitness under various mechanisms. Add 99%-100% dark chocolate and exercise, both of which act similarly to PQQ. Theanine for increasing GABA, primary calming neurotransmitter.
I back this up as a human who is doing 90% of these and has a daily A/B test of perceived energy balance and endurance difference depending on using them.
Thank you for the tip about DCA!
> If you need oxygen, then you need sleep!
Would this also correlate with the desire to yawn? I always heard that yawning was a response to needing more oxygen.
It has nothing to do with oxygen; Yawning is caused by other people yawning in the vicinity.
Of course not. Sympathy yawning is a thing of course, but have you never yawned by yourself with no one around?
This isn’t the case for my dog or infant.
They remembered a yawn
I’m drawing a connection here between red light therapy being most beneficial if done in the morning.
Might mitochondria only be able to benefit from “recharging” in a recharge state?
Biochemists?
When he says lack of "restorative" sleep, he means stage III NREM? I wish he were more precise.
Given its role in energy transfer, does this suggest creatine might be a good supplement for improving sleep?
That's a bizarre coincidence. For the past few days I've run across a bunch of accounts of people taking more creatine than suggested (10-20g a day). They seem to all talk about how it makes them work better during sleep deprivation. So the answer seems like it helps.
Do you have any links? This is interesting
I’ve seen some social media posts in the last week by Rhonda Patrick discussing 20g/day for cognitive benefits.
Can’t find that post, but here is a breakdown of claims from an interview she conducted a few months ago: https://www.reddit.com/r/Supplements/comments/1jo8pk8/my_top...
I mean there are studies that show this as well. Not the improved sleep, but help in sleep deprivation scenarios
It’s a rational expectation. Improves phosphate transport for more efficient or unbottlenecked ATP synthesis.
Everyone should use creatine. It’s not just for bros.
My sleep gets worse when I take creatine, so maybe it doesn't improve sleep, but rather helps mitochondria to get by without sleep?
Mitochondria health all comes down to sleep.
This has been known for a long time to those interested in the field.
The mitochondria is the powerhouse of the cell
I wonder is this why creatine gives me more energy?
"This also strongly suggests that sleep and hunger are both tied to mitochondrial function and energy balance (the latter was already pretty clear!), and that aerobic organisms are constantly adjusting for both fueling their mitochondria and giving them (especially the ones in the central nervous system) some down time for repair and recovery. As the authors say, rather eloquently, “electrons flow through the respiratory chains of the respective feedback controllers like sand in the hourglass that determines when balance must be restored”. 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!"
yawn :) I was wondering if sleep and hunger are tied to mitochondrial function, then wouldn't breathing be affected? If you're hungry, you're not getting enough glucose for respiration. If you're suffocating....
The heart beats non-stop and doesn't sleep. How does this fit with this theory?
I was thinking along the same lines, but bigger. Mitochondria don't "shut down" when we sleep. If they did, we would die very quickly. If anything, they produce quite a bit of energy during things like REM sleep and digestion. I'm sure I'm missing some subtle details about HOW they "rest", but from a 30000 ft view, it's puzzling.
The paper's core idea isn’t that all cells that use mitochondria need sleep, but rather:
> In a specific subset of sleep-inducing neurons, mitochondrial electron leak builds up when energy is available but underused during neuronal inactivity. That mismatch acts as a sleep signal.
The heart doesn’t fall into that subset.
So lack of sleep damages thr little critters.
I don't know if I can buy this explanation. Sleep is dangerous (and not just to night drivers). You're basically in a several-hours-long coma where a smilodon can come along and eat you without any trouble. So long as cells have more than one mitochondria each, staging them so they don't all need sleep simultaneously seems like a total no-brainer, and doesn't require any difficult-to-manage circumstances that leave you unconscious as predator snacks. This is a big deal, there's more than enough evolutionary pressure for sleep to have been selected out of the genome hundreds of millions of years ago.
The body system is almost never one thing that drives it, especially sleep
the powerhouse of the cell
Funded primarily by UK and European taxpayers and foundations via 8 grants, predominantly from the Wellcome Trust, with additional support from EU research council and Swiss science programs.
ah yes the mitochondria ... the powerhouse of the cell. thanks Ms Jeffers 7th grade bio
Crazy. If true this solves the question why humans need sleep and could be a great direction to resolve further question about sleep diseases.
mitochondria are just so incredibly fascinating in every aspect
they are like another lifeform not just living in our lifeform but making it possible
even their mere existence might be alien or even explain the lack of alien life detected so far
PBS Space Time has yet another awesome episode on that
https://www.pbs.org/video/is-there-a-simple-solution-to-the-...
https://www.youtube.com/watch?v=abvzkSJEhKk
Happy to read that they didn't go for 'Mitochondria Are All You Need', such titles are making me tired
Sleep is all you need, then?
Mitochondria, power douse the self?
How far away are we from making this a pill? So we can stay up 18 hours a day, or something. Any estimates.
Any idea what foods or current methods, to trigger the same mechanism?
You are describing slow-wave enhancement. It's what we've been working on at https://affectablesleep.com, not with the goal of letting people sleep less time, but with the goal of enhancing the restorative function of sleep without altering sleep time.
Measuring sleep by time makes about as much sense as measuring your diet based on how much time you spend chewing.
Sleep isn't about time, it's about restorative function.
There is no one diet for everyone, no one exercise regimen for everyone, why would we think sleep is any different.
We don't promote sleeping less. We're not the sleep police. We aim to ensure the sleep you get is as beneficial as possible.
Pre-sales are opening soon.
You mean operating on 6 hours of sleep? That doesn't seem that extreme. Perhaps less than ideal, but plenty of people seems to handle it fine.
Please not, the economy will simply expand until everyone needs to work longer.
>So we can stay up 18 hours a day, or something
That's called having a kid.
Electrons are all you need
It’s quantum particles all The way down.
Turtle shaped quantum particles
Isn't mitochondria the hot new topic du jour (last couple of years) for bio? Is this kind of peak hype cycle?
Science follows the exact same cycle as tech ... I feel like the microbiome was huge and going to solve all our problems 8 years ago.
I don't want to sound jaded but history repeats itself in echoes - and these cycles seem somewhat predictable if the specific technology isn't predictable.