> Orexin antagonists (which block the molecules’ actions rather than mimicking it, and thus promote sleep), have been available since 2014 as treatments for insomnia. They work differently from conventional sleeping pills, which enhance GABA, one of the brain’s main inhibitory neurotransmitters. Birgitte Kornum, an expert on orexins at the University of Copenhagen, says such pills induce sedation rather than natural sleep and often lose effectiveness with continued use. Orexin antagonists instead turn down the brain’s wakefulness signal, letting its sleep-promoting systems take over. Evidence suggests this produces better sleep, with less risk of dependence and fewer long-term problems.
Why? Cleaning is easy to optimize yet sleep is evidently hard to optimize. Going unconscious for a big chunk of the day in a world where everything wants to eat you is a crazy price to pay, yet sleep is highly conserved across species under this extreme selective pressure. Even the animals famous for avoiding sleep don't really avoid sleep so much as bend the rules! Seals partially wake up to breathe, migrating birds sleep a hemisphere of their brain at a time, but they all sleep. This didn't happen because "pumps are slow" or "filtering is hard." Biology is excellent at copy-paste-reinventing that stuff. Optimizing the pumps and filters is not something evolution would have struggled to do if it could have meant not going unconscious for a third of the day. Especially for organisms with small brains where the transport logistics are trivial.
IMO the much more likely explanation is that the brain uses contrastive learning somewhere. We know animal brains don't use backpropagation to train and contrastive learning is one of the biggest competing family of techniques. Instead of using calculus and outer products to calculate derivatives, you feed real data and false data forward through the network and each neuron tracks and trains on the difference. This can be batched -- many CL techniques could handle 16 hours of real data followed by 8 hours of false data -- but the false data can't be put off forever, or the contrast signal goes away. Also, you probably want to inactivate I/O while the false data is flowing through. In other words: sleep emerges from first-principles on the category of neural network learning techniques that the brain probably uses.
I don't think anyone was seriously about to shoot up with sleep-replacement peptides, but also: don't. Let someone else figure this out the hard way.
This doesn’t explain sleep in virtually brainless creatures. A metabolic root cause seems more likely.
Could you make the case for metabolic explanations? Are there a bunch of coupled mechanisms that all require downtime and couldn't possibly be phased?
There is virtually no parrelel between both worlds besides the naming and no one has any idea about what's going on for real.
The closest thing now is amphetamine but it turns people into maniacs - presumably the action here is not actually the brain cleaning function of sleep, rather just preventing reuptake of neurotransmitting chemicals that would cause it, if allowed.
Would be nice to truly provide the mechanism in a synthetic form - I wonder what it would feel like to have the brain “slept” while awake.
Turning off that misfiring with drugs would be dangerous (pain is an alert) but also improve the quality of life of so many people!
I've only had two instances where I ignored all the signs and continue to push on until my body literally shut down on me. Finals week in college as an architecture student trying to finish a final studio project, and study for four finals. 5 days, 3 hours of sleep. That was one of them.
Regardless, I'm stuck in captcha hell whenever I try to reach them (I've tried switching browsers and DNS servers, no luck).
> Orexins are made by a small number of neurons in the hypothalamus, a brain region tucked behind the eyes.
https://sleep.hms.harvard.edu/education-training/public-educ...
Neurons synthesize proteins [1]. (I think glia do the heavy lifting.)
[1] https://brain.mpg.de/164308/protein-supply-in-long-nerves-ho...
Do people drinking coffee in the morning *abuse* it?
https://link.springer.com/article/10.1007/s40979-024-00174-3
I remember there being kind of a burst of articles about it on HN about ten or fifteen years ago, with a lot of commenters talking about their use of it.
If I'm not mistaken there was an experiment using fruit flies where they fed them antioxidants and that made them not die from lack of sleep.
Also, orexins are peptides, like semaglutide (Ozempic), although in a different family.
The sad fact is that people will be pressured into taking this.
E: Lindy was probably the wrong term. But still, it's like Chesterton's fence. We are far from fully understanding human biology... and deleting sleep will lead to unknown effects. All power to those who try, I guess.
>comedians do not have a fixed amount of comedic material to spread over TV appearances, but rather, the more appearances they make, the more future appearances they are predicted to make
sure, but earlier it says that it does not apply to humans because the Lindy effect would imply that a 100 year old would have more life left than an 11 year old, which is counterintuitive, but the example given above would imply George Burns had more television appearances left to do at the age of 99 than Macaulay Culkin at the age of 9, which is just a layer of abstraction laid over the biological age property.
Two things you'll always find someone to defend with vigor are sleep and death. A lot of humans seem to despise living in general. It's fascinating to see.
The latter half of your comment is rather smug, but I wouldn't look down on people who have peacefully accepted reality. Time is fleeting and we are but flowers in a field—briefly brightly bloomed and then withered.
I mean, I can directly feel the benefit of a good sleep that refreshes me in the morning, whereas there's those who have passed on whom I miss.
If I didn't need sleep, really didn't, I wouldn't seek to re-invent it; but of the two it is old age that I'd actively pay money to hold back, if treatments for both existed at the same cost per extra hour of consciousness in my lifetime.
It's because if it were achieved, likely result would be employers forcing people to take the drug and increasing daily work hours back to 16+.
How so? You can just... refuse? And do you prefer sleeping to working? Doing a job that you hate for 8h and sleeping for 8h is much worse than doing a job that you love for 16h. Something to think about.
Ozempic is for sure a miracle for some who really need it but for many I think they would be better off by solving that problem at the source (likely gut bacteria based and consuming a better mix of prebiotic fibers). Increase your natural levels of GLP-1
Why can’t we synthesize vitamin C?
The root-cause solution to vitamin C deficiency is supplementation (through food or otherwise). If our bodies couldn’t figure something like this out, something the rest of the animal kingdom (apart from guinea pigs) did, it strikes me as conceivable is badly optimized in other cases, too.
But our bodies also figured out that for an extended period of time this ability was useless since vitamin C was so readily available in all our food sources in most circumstances.
But none of the other animals in our biomes similarly optimized? Including none of the other apes?
The less Panglossian interpretation is a gene got fucked up, it didn't wipe us out, and the fuck-up got conserved because it doesn't kill us before reproduction, it just makes us sicker from time to time.
That's pretty easy: The last centuries (or decades, mostly) have provided an asymmetry in nutrition systems. Modern food engineering has optimized most of what people eat to have them crave more instead of being mainly filling. There is little to counter that, and GLP-1 is a way to do that. Another way is will power. Yet another is fixing what and how you eat (and how you exercise, but that'a a different topic).
Plus it's not like you couldn't combine a GLP-1 drug with great diet and exercise
But prescribing diet and exercise alone has long had mixed results, because it does nothing to address appetite, and it is even quite common for exercise to increase it.
Empirically untrue. GLP-1s outperform diet and exercise alone.
> it's not like you couldn't combine a GLP-1 drug with great diet and exercise
This is how it's recommended to be taken. I personally know folks who were able to start regularly exercising and eating healthily because of the head start GLP-1s gave them. (They're mostly off them now, and they're all materially lighter and healthier than they were before.)
Imagine Grog and gang kill a mammoth but Grog only eats 500 calories before feeling so full he's going to throw up.