Sleep all comes down to the mitochondria

https://www.science.org/content/blog-post/it-all-comes-down-mitochondria

by A_D_E_P_T • 12 months ago

639 292 12 months ago

A_D_E_P_T4• 12 months 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• 12 months ago

What would happen to the main and brain with "Healthy" wakefulness promoting drugs .

can16358p2• 12 months ago

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.

kbrkbr• 12 months 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.

lolive2• 12 months ago

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\

yreg2• 12 months ago

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.

eutropia• 12 months ago

TFA also acknowledges this:

  > 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!

steve1977• 12 months ago

It might have one evolutionary root cause and then got hijacked for other uses as well.

ge963• 12 months ago

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.

legohead• 12 months ago

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.

bsenftner• 12 months ago

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.

eastbound• 12 months ago

Cocaine and amphetamines, for a lot of them ;)

portaouflop• 12 months ago

They have a different gene expression which leads to them needing less sleep.

drw85• 12 months ago

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.

dboreham• 12 months ago

They could also be liars.

meindnoch2• 12 months ago

[citation needed]

DiggyJohnson• 12 months ago

Stimulants and embellishment (potentially inadvertent)

bearl• 12 months ago

We microsleep whenever we blink. Or at least that was the old science, maybe there’s a new explanation.

alphazard3• 12 months 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.

FrustratedMonky3• 12 months ago

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.

hackyhacky• 12 months ago

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.

andrewflnr4• 12 months ago

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.

maerF0x0• 12 months ago

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?

HarHarVeryFunny5• 12 months ago

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.

Symmetry3• 12 months ago

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.

nonameiguess• 12 months ago

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.

layer8• 12 months ago

"Healthy" restorative-sleep drugs might be even more useful. Would these new insights help with that?

0xbadcafebee• 12 months ago

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.

ralfd• 12 months ago

I understand some of these words. Explain like I am 15?

0xEF• 12 months ago

The mitochondria is the powerhouse of the cell. Sometimes that powerhouse needs to be tidied up.

superfrank• 12 months ago

Your brain is like a server and the way mitochondria make energy is like a slow memory leak. Sleep is like running garbage collection.

profstasiak• 12 months ago

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

llamasushi• 12 months ago

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.

CGMthrowaway2• 12 months ago

Does it explain why we need sleep? My read was it explains why we get sleepy.

Xss3• 12 months ago

Iirc it is adenosine build up that makes us sleepy

timr4• 12 months 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.

ajkjk2• 12 months ago

a completely unnecessary interjection

"might have been answered" is absolutely valid: the correct theory might have been produced

mrbungie2• 12 months ago

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.

m3kw92• 12 months ago

what about the brain flushing mechanism that won the nobel prize?

oc1• 12 months ago

Crazy. If true this solves the question why humans need sleep and could be a great direction to resolve further question about sleep diseases.

amelius• 12 months ago

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 ...

chasil• 12 months ago

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/

alphazard3• 12 months ago

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_...

omnibrain• 12 months 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• 12 months ago

As someone who has been recently floxed by antibiotics, life has become miserable for me.

geuis• 12 months ago

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.

bigDinosaur• 12 months ago

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'.

beacon294• 12 months ago

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.

phtrivier• 12 months ago

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) ?

A_D_E_P_T4• 12 months ago

Speculative: Gentle mitochondrial uncouplers that cross the BBB very well, possibly in conjunction with elamipretide, MitoQ, MitoTEMPO, or something similar.

kridsdale19• 12 months ago

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.

storus• 12 months ago

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.

kridsdale19• 12 months ago

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!

robwwilliams3• 12 months ago

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

HarHarVeryFunny5• 12 months ago

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.

beerws• 12 months ago

Happy to read that they didn't go for 'Mitochondria Are All You Need', such titles are making me tired

manmal• 12 months ago

Sleep is all you need, then?

jijijijij• 12 months ago

Mitochondria, power douse the self?

skeezyboy2• 12 months ago

i wonder if it relates to that chronic laziness disease, i cant remember what its called

skeezyboy2• 12 months ago

Fibromyalgia

qiine• 12 months ago

hu no ?

smallerfish• 12 months ago

Vibe coding

petesergeant• 12 months ago

Myalgic encephalomyelitis (ME) might be what you're thinking, although I think generally it's described as chronic _fatigue_ rather than laziness.

ck22• 12 months ago

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...

gediz• 12 months ago

ADHD?

satvikpendem3• 12 months ago

Chronic fatigue syndrome?

purerandomness• 12 months ago

ME/CFS?

robwwilliams3• 12 months ago

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

henryaj• 12 months ago

Given its role in energy transfer, does this suggest creatine might be a good supplement for improving sleep?

Aerroon• 12 months ago

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.

rafaelmn• 12 months ago

I mean there are studies that show this as well. Not the improved sleep, but help in sleep deprivation scenarios

parliament32• 12 months ago

Do you have any links? This is interesting

BiteCode_dev• 12 months ago

My sleep gets worse when I take creatine, so maybe it doesn't improve sleep, but rather helps mitochondria to get by without sleep?

ck22• 12 months ago

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

FrustratedMonky3• 12 months ago

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?

Bjartr• 12 months ago

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.

17186274403• 12 months ago

Please not, the economy will simply expand until everyone needs to work longer.

meindnoch2• 12 months ago

So we can stay up 18 hours a day, or something

That's called having a kid.

pedalpete• 12 months ago

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.

aussieguy1234• 12 months ago

Electrons are all you need

kridsdale19• 12 months ago

It’s quantum particles all The way down.

KingFelix• 12 months ago

Turtle shaped quantum particles

niemandhier• 12 months 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

the__alchemist• 12 months ago

Perhaps sand won't save you this time, but this sand will save you time.

satvikpendem3• 12 months ago

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.

brbrodude• 12 months ago

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..

satvikpendem3• 12 months ago

Perhaps in your dad's case, it's despite, not because.

JCM9• 12 months ago

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.

jajko• 12 months ago

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.

andruby2• 12 months ago

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?

soulofmischief3• 12 months ago

Maybe some people just enjoy working.

keysdev• 12 months ago

One best things about getting laid off from work is that one get to sleep as long as one want in the morning!

andruby2• 12 months ago

I don't think this person has children :P

ge963• 12 months ago

Or binge watch the entire Walking Dead series in a month

kridsdale19• 12 months ago

Yes, that’s the “lay” that you will be doing.

derbOac• 12 months ago

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.

crocowhile2• 12 months ago

It is an awful paper and I am a very expert in this area. This is science, alas.

flobosg2• 12 months ago

Not an expert, but I’d love to hear more about what makes it awful.

kridsdale19• 12 months ago

Please elaborate.

ed• 12 months ago

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

Tokumei-no-hito• 12 months ago

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?

Symmetry3• 12 months ago

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.

nialse2• 12 months ago

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.

type0• 12 months ago

there's this prion disease https://en.wikipedia.org/wiki/Fatal_insomnia

Symmetry3• 12 months ago

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.

ashoeafoot• 12 months ago

So lack of sleep damages thr little critters.

lr4444lr2• 12 months ago

When he says lack of "restorative" sleep, he means stage III NREM? I wish he were more precise.

dist-epoch• 12 months ago

The heart beats non-stop and doesn't sleep. How does this fit with this theory?

Rooster61• 12 months ago

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.

SalariedSlave• 12 months ago

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.

dbagr• 12 months ago

This has been known for a long time to those interested in the field.

boringg• 12 months ago

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.

HarHarVeryFunny5• 12 months ago

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.

baq2• 12 months ago

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)

HarHarVeryFunny5• 12 months ago

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.

pitched2• 12 months ago

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.

emsign2• 12 months ago

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.

rogerkirkness2• 12 months ago

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...

azinman22• 12 months ago

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

francisofascii• 12 months ago

Isn’t simply getting enough outdoor sunlight just as good as red light therapy.

azinman22• 12 months ago

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”.

emsign2• 12 months ago

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.

Lazare2• 12 months ago

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".

kridsdale19• 12 months ago

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.

gavinray• 12 months ago

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.

robwwilliams3• 12 months ago

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

baggachipz• 12 months 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.

_9ptr2• 12 months ago

It has nothing to do with oxygen; Yawning is caused by other people yawning in the vicinity.

williamdclt• 12 months ago

Of course not. Sympathy yawning is a thing of course, but have you never yawned by yourself with no one around?

kridsdale19• 12 months ago

This isn’t the case for my dog or infant.

searine• 12 months 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.

bluechair• 12 months ago

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?

lawlessone• 12 months ago

I wonder is this why creatine gives me more energy?

dangoodmanUT• 12 months ago

the powerhouse of the cell

m3kw92• 12 months ago

The body system is almost never one thing that drives it, especially sleep

bobafett-9902• 12 months ago

ah yes the mitochondria ... the powerhouse of the cell. thanks Ms Jeffers 7th grade bio

NoMoreNicksLeft• 12 months ago

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.

andrethegiant• 12 months ago

The mitochondria is the powerhouse of the cell

bmillare• 12 months ago

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.

pitched2• 12 months ago

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.

tgbugs• 12 months ago

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

profsummergig• 12 months ago

Mitochondria health all comes down to sleep.

kwoff• 12 months 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• 12 months ago

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.

rajnathani• 12 months 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• 12 months ago

ahh yes. the powerhouse of the cell

OrangeMusic• 12 months ago

Wait... Flies sleep?!

Sleep all comes down to the mitochondria

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