18 ms·
Sleep all comes down to the mitochondria
- ashoeafoot 1y agoSo lack of sleep damages thr little critters.
- A_D_E_P_T 1y agoSo 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.
- v3ss0n 1y agoWhat would happen to the main and brain with "Healthy" wakefulness promoting drugs .
- can16358p 1y agoProbably 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.
- A_D_E_P_T 1y agoThat'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.
- can16358p 1y agoAnd exactly as I said, Ozempic does more harm in the long run.
- drgiggles 1y agoThere 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.
- immibis 1y agoReminds me of the alleged neurological benefits from use of hallucinogenics - but they're still banned.
- jobs_throwaway 1y agosource?
- mwigdahl 1y agoProof? 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.
- hyghjiyhu 1y agoThat'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.
- kbrkbr 1y ago> 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.
- lolive 1y agoAI frenzy almost convinced me that sleep was the training of our neural network with all the prompts of the day. And now this /o\
- ozgung 1y agoThat'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 https://en.wikipedia.org/wiki/Wake-sleep_algorithm
- dr_dshiv 1y agoWhen 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.
- bsenftner 1y agoI'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.
- eastbound 1y agoCocaine and amphetamines, for a lot of them ;)
- portaouflop 1y agoThey have a different gene expression which leads to them needing less sleep.
- drw85 1y agoI 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.
- dboreham 1y agoThey could also be liars.
- meindnoch 1y ago[citation needed]
- DiggyJohnson 1y agoStimulants and embellishment (potentially inadvertent)
- bearl 1y agoWe microsleep whenever we blink. Or at least that was the old science, maybe there’s a new explanation.
- SamBam 1y ago
- alphazard 1y ago> 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.
- FrustratedMonky 1y agoNot 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.
- alphazard 1y agoIt'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.
- FrustratedMonky 1y agoThat'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.
- Symmetry 1y agoThis 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.
- CGMthrowaway 1y agoDoes it explain why we need sleep? My read was it explains why we get sleepy.
- Xss3 1y agoIirc it is adenosine build up that makes us sleepy
- CGMthrowaway 1y agoThe 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.
- nonameiguess 1y agoIt'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.
- layer8 1y ago"Healthy" restorative-sleep drugs might be even more useful. Would these new insights help with that?
- 0xbadcafebee 1y agoIt'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.
- ralfd 1y agoI understand some of these words. Explain like I am 15?
- 0xEF 1y agoThe mitochondria is the powerhouse of the cell. Sometimes that powerhouse needs to be tidied up.
- superfrank 1y agoYour brain is like a server and the way mitochondria make energy is like a slow memory leak. Sleep is like running garbage collection.
- profstasiak 1y agowould 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
- llamasushi 1y agoPiggybacking 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.
- timr 1y ago> 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.
- ajkjk 1y agoa completely unnecessary interjection "might have been answered" is absolutely valid: the correct theory might have been produced
- timr 1y agoOn 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.
- ajkjk 1y agoIt 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.
- mrbungie 1y agoI 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.
- m3kw9 1y agowhat about the brain flushing mechanism that won the nobel prize?
- oc1 1y agoCrazy. If true this solves the question why humans need sleep and could be a great direction to resolve further question about sleep diseases.
- amelius 1y agoSomething 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 ...
- chasil 1y agoIt 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/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8301944/
- alphazard 1y agoIt'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_uptake https://en.wikipedia.org/wiki/Quinolone_antibiotic#Cellular_...
- omnibrain 1y ago> 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.
- phyphy 1y agoAs someone who has been recently floxed by antibiotics, life has become miserable for me.
- geuis 1y agoBe 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.
- phtrivier 1y agoSo, 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) ?
- A_D_E_P_T 1y agoSpeculative: Gentle mitochondrial uncouplers that cross the BBB very well, possibly in conjunction with elamipretide, MitoQ, MitoTEMPO, or something similar.
- kridsdale1 1y agoWould 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.
- A_D_E_P_T 1y agoYeah, 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.
- storus 1y agoI 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.
- kridsdale1 1y agoI 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!
- beerws 1y agoHappy to read that they didn't go for 'Mitochondria Are All You Need', such titles are making me tired
- skeezyboy 1y agoi wonder if it relates to that chronic laziness disease, i cant remember what its called
- skeezyboy 1y agoFibromyalgia
- qiine 1y agohu no ?
- deleted 1y ago[deleted]
- smallerfish 1y agoVibe coding
- petesergeant 1y agoMyalgic encephalomyelitis (ME) might be what you're thinking, although I think generally it's described as chronic _fatigue_ rather than laziness.
- ck2 1y agoYes 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-experimental-trial-to-challenge-age-limits/ https://longevity.technology/news/physicist-90-joins-experim...
- tonyedgecombe 1y ago[flagged]
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- henryaj 1y agoGiven its role in energy transfer, does this suggest creatine might be a good supplement for improving sleep?
- Aerroon 1y agoThat'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.
- rafaelmn 1y agoI mean there are studies that show this as well. Not the improved sleep, but help in sleep deprivation scenarios
- kridsdale1 1y agoIt’s a rational expectation. Improves phosphate transport for more efficient or unbottlenecked ATP synthesis. Everyone should use creatine. It’s not just for bros.
- parliament32 1y agoDo you have any links? This is interesting
- jayunit 1y agoI’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_10_takeaways_from_rhonda_patricks_podcast/ https://www.reddit.com/r/Supplements/comments/1jo8pk8/my_top...
- BiteCode_dev 1y agoMy sleep gets worse when I take creatine, so maybe it doesn't improve sleep, but rather helps mitochondria to get by without sleep?
- ck2 1y agomitochondria 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-fermi-paradox-exhglt/ https://www.pbs.org/video/is-there-a-simple-solution-to-the-... https://www.youtube.com/watch?v=abvzkSJEhKk https://www.youtube.com/watch?v=abvzkSJEhKk
- FrustratedMonky 1y agoHow 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?
- Bjartr 1y agoYou 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.
- 1718627440 1y agoPlease not, the economy will simply expand until everyone needs to work longer.
- meindnoch 1y ago>So we can stay up 18 hours a day, or something That's called having a kid.
- pedalpete 1y agoYou are describing slow-wave enhancement. It's what we've been working on at https://affectablesleep.com 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.
- aussieguy1234 1y agoElectrons are all you need
- kridsdale1 1y agoIt’s quantum particles all The way down.
- KingFelix 1y agoTurtle shaped quantum particles
- niemandhier 1y ago"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 https://www.nature.com/articles/nature.2013.14196
- the__alchemist 1y agoPerhaps sand won't save you this time, but this sand will save you time.
- satvikpendem 1y agoI 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.
- mynameisvlad 1y ago[flagged]
- satvikpendem 1y agoI 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.
- mynameisvlad 1y ago[flagged]
- satvikpendem 1y ago> 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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- JCM9 1y agoSleep 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.
- jajko 1y agoWorkaholism 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.
- andruby 1y agoI'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?
- starluz 1y ago[dead]
- mock-possum 1y agoNot ‘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.
- soulofmischief 1y agoMaybe some people just enjoy working.
- derbOac 1y agoThe paper is here: https://www.nature.com/articles/s41586-025-09261-y 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.
- crocowhile 1y agoIt is an awful paper and I am a very expert in this area. This is science, alas.
- flobosg 1y agoNot an expert, but I’d love to hear more about what makes it awful.
- kridsdale1 1y agoPlease elaborate.
- crocowhile 1y agoThe 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.
- flobosg 1y ago“They hyped their conclusions a lot” is par of the course, but > the sleep phenotype itself is basically non-existing is not. Can you explain that in more detail?
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- Symmetry 1y agoCould 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.
- nialse 1y agoWhile 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.
- type0 1y agothere's this prion disease https://en.wikipedia.org/wiki/Fatal_insomnia https://en.wikipedia.org/wiki/Fatal_insomnia
- downrightmike 1y agoAnd there is the hereditary version: fatal familial insomnia [FFI]) stemming from a mutation in the PRNP gene.
- nialse 1y agoYes, 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.)
- Symmetry 1y agoI'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.
- lr4444lr 1y agoWhen he says lack of "restorative" sleep, he means stage III NREM? I wish he were more precise.
- dist-epoch 1y agoThe heart beats non-stop and doesn't sleep. How does this fit with this theory?
- Rooster61 1y agoI 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.
- SalariedSlave 1y agoThe 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.
- dbagr 1y agoThis has been known for a long time to those interested in the field.
- boringg 1y agoIsn'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.
- HarHarVeryFunny 1y agoThere 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.
- baq 1y agothe 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)
- HarHarVeryFunny 1y agoBut 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.
- kridsdale1 1y agoThe 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.
- HarHarVeryFunny 1y agoWe'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.
- emsign 1y agoIncreasing the count and efficiency of mitochondria is gonna be a big deal. ME/CFS is caused by these organelles not working as they should.
- rogerkirkness 1y agoHighly 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/1ZKl5Me4XwPj4YgJCBes3VSCJjiVO4XI0tIR0rbMBj08/edit#gid=0 https://docs.google.com/spreadsheets/u/1/d/1ZKl5Me4XwPj4YgJC...
- azinman2 1y agoThat’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
- ulf-77723 1y agoWould 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.
- francisofascii 1y agoIsn’t simply getting enough outdoor sunlight just as good as red light therapy.
- rogerkirkness 1y agoYes, assuming you get exactly the right amount and somehow also never too much of the bad UV light. It's a finicky thing to get right, but bottom line yes.
- baggachipz 1y ago> 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.
- _9ptr 1y agoIt has nothing to do with oxygen; Yawning is caused by other people yawning in the vicinity.
- williamdclt 1y agoOf course not. Sympathy yawning is a thing of course, but have you never yawned by yourself with no one around?
- kridsdale1 1y agoThis isn’t the case for my dog or infant.
- _9ptr 1y agoThey remembered a yawn
- searine 1y agoFunded 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.
- bluechair 1y agoI’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?
- lawlessone 1y agoI wonder is this why creatine gives me more energy?
- dangoodmanUT 1y agothe powerhouse of the cell
- m3kw9 1y agoThe body system is almost never one thing that drives it, especially sleep
- bobafett-9902 1y agoah yes the mitochondria ... the powerhouse of the cell. thanks Ms Jeffers 7th grade bio
- NoMoreNicksLeft 1y agoI 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.
- andrethegiant 1y agoThe mitochondria is the powerhouse of the cell
- bmillare 1y agoTo 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.
- pitched 1y agoChatGPT 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.
- tgbugs 1y agoThe 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 https://en.wikipedia.org/wiki/Familial_natural_short_sleep
- profsummergig 1y agoMitochondria health all comes down to sleep.
- kwoff 1y ago"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....
- BrenBarn 1y agoTo 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.
- rajnathani 1y ago> .. 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).
- casey2 1y agoahh yes. the powerhouse of the cell
- OrangeMusic 1y agoWait... Flies sleep?!