I feel like I'd want the opposite of this - something that mimics the cleaning process of sleep that you could use in the afternoon for a nap or etc.
smallmancontrov 5 minutes ago [-]
Sleep isn't about cleaning. It might include cleaning, but I don't believe for a second that cleaning is the main function.
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.
redox99 2 minutes ago [-]
I think you overestimate the disadvantages of sleep. It's very species dependent, for some it might be a disadvantage because you're more vulnerable to predators, for others it's an advantage because you spend less energy. If you're safe you really only need enough wake time to eat and reproduce.
smallmancontrov 1 minutes ago [-]
If you're safe.
JumpCrisscross 1 minutes ago [-]
> the much more likely explanation is that the brain uses contrastive learning somewhere
This doesn’t explain sleep in virtually brainless creatures. A metabolic root cause seems more likely.
volkercraig 19 minutes ago [-]
If you want something that displaces adenosine from your neurons you are in luck, because it already exists and is very easy to get; It's called methamphetamine
voidfunc 11 minutes ago [-]
Excellent, but now I have a new problem: An addiction to meth.
ssl-3 10 minutes ago [-]
Is that worse than an addiction to sleep?
redox99 31 seconds ago [-]
Do not, my friends, become addicted to sleep. It will take hold of you, and you will resent its absence!
strictnein 47 minutes ago [-]
By mimic do you mean it does the cleaning process or just that you feel like it did? If it was the former, that would be very interesting.
hamdingers 42 minutes ago [-]
The latter is how caffeine works. Blocks adenosine receptors so you don't feel tired even though you are.
Gooblebrai 34 minutes ago [-]
If you don't feel tired, are you really? I'm curious what are the objective metrics to determine someone is tired
npunt 29 minutes ago [-]
Tiredness is a signal that the body/brain needs rest so the glymphatic system can go to work. You can lose the signal but still need rest. If your brain doesn't flush metabolic waste periodically you develop brain fog, bad memory, and increased risk of Alzheimer's, and you'll eventually die, as sleep deprivation studies have found.
burningChrome 8 minutes ago [-]
You have the ability to mentally push through a lot of stuff, but there are a host of signals your body will use to warn you such as: cognitive performance (although this is hard for yourself to actually admit its happening), behavioral indicators like yawning, head bobbing, frequent posture changes, and slowed speech are just a few indicators. Irritability is another big red flag.
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.
odo1242 31 minutes ago [-]
Caffeine doesn't actually do any of the things sleep does to your brain. If you drink coffee during a late night, you won't feel as tired, but your brain performs worse, your reflexes are slower, you're less likely to remember things, etc. It's like painting over a rusted car instead of properly maintaining it, basically.
binary132 18 minutes ago [-]
I think GP was just making a point about the fact that “tired” is a subjective experience, like pain. Arguably, if you’re on pain medication, you’re not in pain, even if your body is sending pain signals that your brain just isn’t receiving or paying attention to.
jkahrs595 26 minutes ago [-]
If I’m on morphine is my leg even still broken?
usui 32 minutes ago [-]
Isn't the answer yes if people still die from overwork despite being caffeined up?
wmf 13 minutes ago [-]
Michael Jackson is the ultimate case study for this.
baueric 17 minutes ago [-]
so the former then
baueric 12 minutes ago [-]
sorry I'm dumb and read it wrong
anigbrowl 24 minutes ago [-]
What if we just normalized taking naps more often?
tayo42 12 minutes ago [-]
I feel like people insist that if you get 8 hours of good sleep you shouldn't need a nap
midtake 29 minutes ago [-]
The article is about modulating orexins in the brain. Orexin receptor agonism was thought to be a mechanism of modafinil/armodafinil but this isn't mentioned anywhere in the article. Modafinil is mentioned as a mere stimulant. It sort of makes me want to dismiss the article as manufactured hype for a new class of modafinil successors.
semiquaver 7 minutes ago [-]
> Orexins are made by a small number of neurons in the hypothalamus, a brain region tucked behind the eyes.
I didn’t know that “neurons” themselves could make peptides, or anything really. Is this accurate terminology or a shorthand?
FeteCommuniste 52 seconds ago [-]
> Orexins are only produced by a small cluster of neurons in the hypothalamus, a brain region located roughly behind the eyes and between the ears.
Not to take away from the broader point, but modafinil is lumped in with methylphenidate as a stimulant that "increase[s] the activity of neurotransmitters such as dopamine and norepinephrine". Modafinil does also stimulate the orexin system and is part of why it's so effective for wakefulness and not as a stimulant in the medium/long-term.
there are variations but some are shady... archive.ph, archive.today, etc. there's probably a central list somewhere.
throw-the-towel 1 minutes ago [-]
archive.today and archive.fo is literally the same service.
pygy_ 16 minutes ago [-]
I thought they were alternative domains for the same service...
Regardless, I'm stuck in captcha hell whenever I try to reach them (I've tried switching browsers and DNS servers, no luck).
tkfoss 15 minutes ago [-]
check URL list on its wikipedia page.
hoppp 51 minutes ago [-]
It sounds to me like something that's quite dangerious. Maybe it helps people with narcolepsy but maybe it will be another thing people abuse like amphetamines?
subscribed 29 minutes ago [-]
Modafinil is available for ages, acts close to this (it's mentioned in the article), and I don't hear of people abusing it.
projektfu 14 minutes ago [-]
It gets abused by people who just want to stay awake, but not in the sense of being a party drug. For example, by students, drivers, security officers, and politicians.
ShinyLeftPad 14 minutes ago [-]
I don't know of anyone using it in the first place...
engineer_22 25 minutes ago [-]
looks like potential for abuse is low - people with normal orexin activity could even experience diminished capacity by these drugs
Fraterkes 15 minutes ago [-]
As an aside, are there any habitual modafinil takers here? I had a period in college where I took it very rarely when I had to cram. Worked pretty well.
d2kx 13 minutes ago [-]
Modafinil has been a lifesaver for me for over a decade, but always great to have more options for medium ADHD.
margorczynski 31 minutes ago [-]
Isn't the problem with lack of sleep (and what causes death with enough deprivation) oxydation that happens in the gut and spreads to the organs?
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.
Liftyee 59 minutes ago [-]
Sleep is Lindy... obesity and constant wakefulness are not.
The sad fact is that people will be pressured into taking this.
andybak 57 minutes ago [-]
Is "Lindy" a typo or have I missed another linguistic innovation?
gottorf 54 minutes ago [-]
Another linguistic innovation[0] -- the idea that things that have been around for a long time are more likely to persist for another long time.
This feels like a stupid heuristic to use if applied to biological forces.
ternaryoperator 37 minutes ago [-]
In the definition of it, living things are specifically excluded.
bryanrasmussen 23 minutes ago [-]
it seems however some things that are not excluded are just one step removed from biological entities, hence
>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.
30 minutes ago [-]
testdelacc1 53 minutes ago [-]
It’s some shit a guy called Taleb came up with. It’s a useful indicator because someone quoting Taleb unironically is someone who can’t tell that Taleb is a midwit.
strictnein 42 minutes ago [-]
I was kind of shocked how bad some of his writing and "logic" were after hearing people rave about his books for years.
FeteCommuniste 18 minutes ago [-]
Checking out his Twitter feed first might have dampened some of that shock.
ben_w 27 minutes ago [-]
I get the vibe, but I wouldn't say shocked, merely disappointed. The Black Swan's point would fit on the book's cover even if printed in the font used for the author's name, the work felt to me like 99% was just garrulous "look at me aren't I smart" padding.
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.
adamtaylor_13 8 minutes ago [-]
Well... Sleep and death are natural. I'm not convinced you see people "defend" death so much as (rightly) acknowledging the inevitability of it.
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.
ben_w 29 minutes ago [-]
Sleep is less surprising for me to see people defend than death, to the extent that I'm not sure if I myself have or not done so.
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.
glerk 23 minutes ago [-]
Obviously, every single one of us needs sleep to survive. But it's a biological chore, not some sacred ritual to be celebrated. Reducing the amount of sleep that we need is worth researching. What is surprising to me is the knee-jerk reaction I see whenever the idea of looking into this is brought up.
Qem 6 minutes ago [-]
> What is surprising to me is the knee-jerk reaction I see whenever the idea of looking into this is brought up.
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+.
FeteCommuniste 21 minutes ago [-]
Even if I never needed to sleep again I would kind of miss dreaming. Maybe we could take another drug to make us dream.
barapa 18 minutes ago [-]
Every conceivable thing 'may be about to' happen.
wesselbindt 12 minutes ago [-]
Literally everything except the media writing non-sensationalist headlines about science.
It's probably the default clickbait title for any article about a new drug.
amarcheschi 58 minutes ago [-]
I like my brain fatty /s
andai 53 minutes ago [-]
You reminded me I need to buy more Omega 3
Melatonic 15 minutes ago [-]
Dont forget Omega 7 and 9 !
bayarearefugee 60 minutes ago [-]
[flagged]
croisillon 34 minutes ago [-]
The brain may be about to have its Algernon moment
FTFY
LogicFailsMe 20 minutes ago [-]
Don't forget the flowers.
Gooblebrai 33 minutes ago [-]
What has anything in this article to do with Ozempic? Is mentioned in the title once and never again. Engagement bait?
projektfu 20 minutes ago [-]
"Hunger and sleep, argues Dan Skovronsky, the firm’s chief scientific officer, are both 'master homeostasis mechanisms'—systems that keep the body in balance. When they misbehave, illness follows. That, he says, helps explain why incretins, the hormone family behind GLP-1, proved so broadly useful. Hence why orexins could be just as important."
Also, orexins are peptides, like semaglutide (Ozempic), although in a different family.
matt_heimer 29 minutes ago [-]
Ozempic == GLP-1 which the first visible paragraph is discussing.
_diyar 23 minutes ago [-]
Ozempic is the poster boy for peptides.
RIMR 26 minutes ago [-]
Your brain is gonna lose so much weight!
FeteCommuniste 20 minutes ago [-]
Neural minimalism, the newest health trend coming to a social network near you.
Melatonic 17 minutes ago [-]
I think the real question with Ozempic is.....why are so many bodies not producing enough natural GLP-1 in the first place?
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).
FeteCommuniste 5 minutes ago [-]
Our "natural" impulse is to eat everything tasty within reach until we're full. That's not so healthy when the tasty stuff regularly includes foods like liter soft drinks, ice cream sandwiches, French fries, and so on. Our bodies didn't evolve with calorie-bombs constantly just a drive-thru trip away.
teiferer 9 minutes ago [-]
> I think the real question with Ozempic is.....why are so many bodies not producing enough natural GLP-1 in the first place?
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).
thinkingtoilet 11 minutes ago [-]
Millions of years of evolution and selection ending up at humans needing one food supply and lifestyle while modern life is basically the opposite. Endless calories. Sugar and meat everywhere. Our bodies are did not evolve for modern life. That's why.
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.
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.
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...
Regardless, I'm stuck in captcha hell whenever I try to reach them (I've tried switching browsers and DNS servers, no luck).
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.
The sad fact is that people will be pressured into taking this.
[0]: https://en.wikipedia.org/wiki/Lindy_effect
>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.
https://en.wikipedia.org/wiki/Lindy_effect#History
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+.
FTFY
Also, orexins are peptides, like semaglutide (Ozempic), although in a different family.
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).
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).