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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 ne
by A_D_E_P_T 1y ago
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.
- 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.
- BobaFloutist 1y agoI mean that would be TPN, where people can be kept alive indefinitely through intravenous fluids (and nutrients).
- 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?