In these conditions it’s more likely that mitochondrial dysfunction is part of the chain of events leading to the fatigue, not necessarily the root cause of the condition.
Also I have to tread very lightly on this topic to avoid giving the wrong idea: Be a little cautious when taking statements about Long COVID and ME/CFS from individuals, as it’s not uncommon for people to present hypotheses as more concrete than the research suggests. With all due respect to Dianna Cowern, some of her past updates on the topic have blurred the lines between conjecture and fact and she’s collaborated with at least one Long COVID / ME/CFS organization that is known for having members that are sometimes less than scientific about their personal theories. It’s a very difficult and complex topic and it can be hard for patients to stay on top of all the different directions the research is looking.
In these conditions it’s more likely that mitochondrial dysfunction is part of the chain of events leading to the fatigue, not necessarily the root cause of the condition.
In other words, it could be more of a symptom than a root cause.
The #1 sign of ME/CFS is post-exertional malaise, which is a delayed crash after even mild exertion, with the crash arriving anywhere from 4-48 hours later, and lasts for days after. Exertion can be taking a shower, thinking hard, etc.
I just recently ruled out ME/CFS for me personally after figuring out that I don't have delayed crashes, but I still haven't figured out source of the fatigue (potentially MCAS?).
Feel free to ask any questions :)
Specialists who treat MCAS are overwhelmed by referrals and requests from patients who don’t meet the criteria or don’t have any basic lab work that suggests MCAS. Many of the diagnoses from primary care or self-diagnoses are from people who have been led to believe that it explains their vague symptoms. There are also a lot of people who believe they have MCAS despite negative labs, non-traditional symptoms and a non-response to medication, which is another way of saying they probably don’t have it.
So watch out. It’s trending among doctors who dabble in alternative medicine or who use it as a catch-all explanation for vague symptoms, but the social media version of MCAS has diverged from the medical definition.
Ehlers-Danlos is another self-diagnoses that is spreading in these communities. This one is so bad that actual Ehlers-Danlos specialists have difficulty sorting through referral requests because so many people and even doctors think it explains vague symptoms. It’s also trending heavily on TikTok.
CCI was briefly popular as an explanation due to a few high profile influencers. For a few years everyone was demanding imaging and sending it to one of a few doctors who specialized in it. Unfortunately those doctors were found to be excessively quick to diagnose. There were a lot of people on forums who rushed into those surgeries with no improvement at all.
Be really careful on the forums. When people start claiming they have a long list of hard to diagnose conditions (MCAS, Ehlers-Danlos, CCI, etc) all at once it’s more likely that they’ve been either self-diagnosing with each trend or they have a doctor who will confirm any vague diagnosis they suggest. These things come in waves of popularity and you can tell when some of these people joined the social media circles by their list of self-diagnoses. Sadly, so much time has been wasted on chasing dead end diagnoses that spread via social media.
> There are also a lot of people who believe they have MCAS despite negative labs, non-traditional symptoms and a non-response to medication
Will agree on non-response, but the typical blood test (tryptase) is not accurate in many cases[2]: "For example, in contrast to proliferative mastocytosis which usually drives significantly elevated tryptase levels, relatively non-proliferative MCAS usually presents with normal tryptase levels;"
> When people start claiming they have a long list of hard to diagnose conditions (MCAS, Ehlers-Danlos, CCI, etc)
Yes and no. [1] is a recent review that finds that these things really are quite comorbid with ME/CFS. All of them at once? Probably not, but a couple is common.
[1] https://www.medrxiv.org/content/10.1101/2024.11.27.24317656v...
[2] https://www.mastcellaction.org/assets/_/2021/09/18/b74c0e90-...
Couple of thoughts:
1. PEM is triggered by things that would be fine for a normal person (walking to car, standing in a line, etc). Over exercising is definitely a thing, but it's not the same as PEM
2. Does the following fatigue cause significant impairment, and does it last for a few days?
There's some other criteria, but those are the first cut.
>I still haven't figured out source of the fatigue (potentially MCAS?).
MCAS is easy to self-diagnose or at least it was in my case. Mast-cell symptoms are triggered by exercise, sun exposure, orgasms and having the connective tissue in your abdomen jiggled (e.g., by riding in a bus with bad suspension along a road with many potholes). For me it is always the same symptoms (fatigue, maybe irritability, maybe a feeling of heat on the skin) regardless of the trigger. Sometimes exposure to one of these things is not enough to trigger symptoms, but then a second exposure before the body has had time to recover from the first exposure will trigger symptoms.
Also (after you remove yourself from any triggers) if the symptoms ameliorate slowly but surely over a period of 2 to 4 hours, that is a pretty strong sign that that the symptoms were caused by mast-cell "granulation" (activation) or at least it is a strong sign in my personal case: I have other chronic conditions that can cause similar symptoms, but if one of the other conditions causes a bout of fatigue or inability to stay productive, the severity of the symptoms will increase and decrease in chaotic or unpredictable ways.
According to him, there should also be at least a couple of active symptoms, such as alternating diarrhea/constipation, edema, skin rashes or hives, foods that are high in histamine, pain while urinating, a constant feeling of being cold, hot flashes, and some others. He also encourages exercise as it helps regulate the immune system.
I certainly don't mean to invalidate your own experience—I know how hard it can be to not be understood—but perhaps there's something else that would explain it better? I'm happy to be corrected :)
I went through a bout of cronic fatigue after a nose surgery that lasted ~4 months and it was utter hell. It really feels like the life has been drained from your body and on top of that, random things go wrong with your body seemingly every day. One day you’ll have strange stomach bloating and feel nauseous, another day you’ll barely be able to stand without fainting, another day you’ll feel heart palpitations, etc.
What made it so much harder to deal with was it’s an invisible illness. Nobody knows about it, and it generally doesn’t show up on tests. The only test that showed anything significant was a tilt-table test where I fainted in the middle of it.
Otherwise I went to the hospital multiple times because I thought I was having a heart attack, I’ve had doctors get angry at me for “wasting their time”, thinking I’m faking it, and friends/family not understanding.
Not to mention having to pretend everything was fine at work. There were times I had to lie down on the bathroom floor to keep myself from fainting or due to heart palpitations. Luckily we had clean, private bathrooms.
As I said, I slowly got better over the course of months, and not everyone is that lucky unfortunately. Honestly if I didn’t get better I probably wouldn’t be here to write this…
Not to trauma dump but a lot of people don’t know about these illnesses or think they’re fake so I wanted to relay my experience.
But be honest: even the surgeons must have been tired after that: 4 months of looking down the same nose - Gaaaaah!
Does that mean in all the cells or only some? Does this damage remain as cells die and get replaced by new ones? Is this damage encoded in the DNA or caused later by COVID?
What I mainly mean is, is this damage getting replicated to new cells as your body generates new ones? AFAIK only DNA affects what new copies of cells will look like, so if it's only caused by COVID later on, what keeps this persistent?
100,000 x 6kbp == 600 million, or less than 1/5 of our genome. Difficult part is the barcoding bits, but that is not THAT hard.
Hundreds to thousands of mitochondria per cell. They also encode pretty few genes, and those genes are mainly there because they directly get injected into the membranes. There are like a thousand mitochondrial genomes per nuclear genome, each with only ~10 genes that repair each other, while the nucleus has literally thousands of mitochondrial genes in two copy. Much easier to look at that
Chloroplasts are a more interesting example of a protein shop. RuBisCO, for example, the most abundant protein on earth, is coded in chloroplasts to scale expression. It is mainly there for dynamic scaling purposes, whereas the mitos are very optimized for one thing
Mitochondria don't go back because if there is 1000 mt genomes to 1 nuclear genome it is extremely energetically desirable to have 1 copy rather than 1000 copies of any given gene.
(FYI I’m not a biologist and have no idea what I’m talking about)
Also don’t forget that mitochondria have their own genome and that it’s undeniable that the avian mito-dna lineage would also experience Darwinian (haha, apt) forces spurring the developments of these capabilities that our ancestors didn’t go through.
But how much has our mitochondria differed in that time?
Source: Boore (1999) Animal mitochondrial genomes. Nucleic Acids Res. 1999 Apr 15;27(8):1767–1780
Hyperlink: https://pmc.ncbi.nlm.nih.gov/articles/PMC148383/
i.e. mtDNA changes a lot less than our "normal" cell nucleus nDNA
Mitochondria Are More Than Powerhouses–They're the Motherboard of the Cell
For efficient respiration, you need to have the translation/transcription of certain ATP synthase genes near to the membrane for basically JIT-ing them when ready to maintain membrane potential, and hence energy generation. Otherwise, the membrane potential falls apart. This simple need is why there are zero multicellular bacteria and multicellularity evolved 6 times in eukaryotes. By decoupling the rest of the genome from the JIT bits (ie, mitochondrial DNA), you can scale energy independently of genetic information. So if you need 1000x the energy, you need like 5% more DNA (mitochondrial DNA) instead of 1000x more DNA in your genome.
Some estimates say that our eukaryotic genes are in charge of 5000x more energy than the equivalent bacterial gene. Hence, our genomes can inflate that much and its fine. And they have. All that inflation lets us have bullshit hang around in our genome, and hey, sometimes evolution figures out something to do with all that bullshit. We evolved 1000x more complexity than bacteria because we decoupled the performance code from the rest of the code.
On the one hand, sure, it's interesting, and the article digs in and is interesting in general -- but that phrase feels off and trite, similar to saying "We were amazed that cheetahs can run over 60mph, while most humans can't manage 10mph" or "We were amazed that sperm whales can hold their breath for 90 minutes while most humans can't manage a minute"
parpfish•8mo ago
neogodless•8mo ago
Too late.
tim333•8mo ago
neogodless•8mo ago
https://www.porsche.com/usa/models/taycan/taycan-models/tayc...
m3kw9•8mo ago
762236•8mo ago
kridsdale1•8mo ago
CGMthrowaway•8mo ago
jchw•8mo ago
I'm not sure most people knew what a turbocharger was to begin with.
nh23423fefe•8mo ago
imagine if i said something like, "after removing all extraneous weight and safety features, my car has been turbocharged."
kinda nonsensical imo, if someone said this i'd just assume they lacked a thesaurus
neogodless•8mo ago
So this isn't too terrible. It's a bit more like overclocking than turbocharging.
A typical ICE turbocharger is a recycler - the exhaust gases are used to spin the turbo which in turn forces air/oxygen into the combustion chamber (cylinder) at a faster rate, which can be tuned alongside fuel intake for increased power.
Of course, this tends to be harder on the engine and must be accounted for in engine design. It's not free, and you don't want every engine to be turbo.
And rather than be good for endurance it's really good for bursts of power.
hinkley•8mo ago
neogodless•8mo ago
In automobiles, if they are powered by something other than exhaust (e.g. electricity) are called "superchargers."
Ah quick web search, I believe they do run off exhaust using "pre-burners" that burn before the burn.
hinkley•8mo ago
mulmen•8mo ago
The Raptor is the first operational Full Flow Staged Combustion rocket engine. https://en.m.wikipedia.org/wiki/Staged_combustion_cycle#Full...
MalbertKerman•8mo ago
SpaceX's advance was going from oxygen rich (where all of the oxidizer and a fraction of the fuel run through the preburner and turbine, as used in the Soviet/Russian engines) or fuel rich (vice versa, used in the Space Shuttle) to full flow (which has both oxygen- and fuel-rich preburners and all of the propellants flow through one turbine or the other).
MalbertKerman•8mo ago
There is one type that comes closer to a turbocharger's operation: the "tap-off cycle" runs the turbine on gas drawn from the main combustion chamber rather than using a separate combustor. Tap-off cycle engines aren't common but Blue Origin and Firefly are using them.
zardo•8mo ago
There are many ways you can make an engine faster. To me the choice of "turbocharger" implies some parallel to the turbochargers actual function, extracting energy from a waste product to process input material at a higher rate.
hinkley•8mo ago
nh23423fefe•8mo ago
we put a turbo in your turbo
hinkley•8mo ago
kridsdale1•8mo ago
Biology is crazy, man.
nh23423fefe•8mo ago
SoleilAbsolu•8mo ago
hinkley•8mo ago
Split the turbocharger into a recovery unit, genset, a supercharger and a battery and no more lag.
MadnessASAP•8mo ago
There are better things you could do to increase engine performance that are lighter, smaller, and cheaper.
Also of you really really want to defeat turbo lag. The easiest way is to seriously delay ignition timing so the fuel is still burning as it enters the turbine leaving more energy for it to extract and therefore staying spooled up.
edit: Not to say your idea wouldn't work, indeed I'd love to see it. Its just not a practical solution. Not that In ever let practicality stop me.
Edit to the edit: https://dieselnet.com/tech/engine_whr_turbocompound.php
https://www.eere.energy.gov/vehiclesandfuels/pdfs/deer_2004/...
So, ya know, disregard everything above.
hinkley•8mo ago
Part of it is that there’s another reason besides a turbo to have a little extra energy left in the exhaust: thermal catalysis of noxious chemicals in the exhaust flow. So there’s a bit of unburned fuel going to the cat for emissions control and people have wondered if we can take some of it back after the converter. For a while every time there was a breakthrough in solid state heat recovery someone mentioned vehicle exhaust.
xeonmc•8mo ago
speedbird•8mo ago
mrguyorama•8mo ago
Like, producing 1 bar of boost for a 2L engine is somewhere between 30-70 hp! Turbos extract that energy from otherwise wasted, extremely hot exhaust gases, which is what makes them efficient. That's also what made them an improvement over supercharging for the majority of applications, because in a supercharger that energy cost comes direct from your usable power.
What "fixed" turbolag in any engine that isn't an 8L diesel is things like variable geometry, lightweight turbines, better bearings, better engine management, and just smaller turbos for the same boost.
It's also massively impacted by driving behavior. My GTI with a teensy tiny turbo still has a half second or so of lag if you try to go from no throttle to full throttle, like if you are really bad at "launching", but if you know what you are doing you will be holding some revs such that the ECU can slap open the throttle plate and dump fuel in just a few cycles and get full 1 bar of boost by the time your clutch is fully engaged. I have done this accidentally more times than I would like to admit, which tends to spin the tires :/
Formula 1 adopted the exact system you are describing, but it's stupid expensive for minimal benefit and I would bet is used more for energy recovery from waste exhaust gasses than actual lag reduction, since F1 cars should be able to almost never be in a regime that would result in lag, and if you have spare joules, you can just throw them directly at the wheels instead of the turbo. It's called the MGU-H system.
gherkinnn•8mo ago
- https://en.wikipedia.org/wiki/Turbo_Pascal
- https://www.specialized.com/il/en/turbo-levo-4-pro/p/4218703...
- https://turbo.hotwired.dev (Drifts right back to turbo charger, but using one as the logo)
Or it can be used to amplify as in "Turbo Clippy":
https://news.ycombinator.com/item?id=42865194
hinkley•8mo ago
jonplackett•8mo ago
acdha•8mo ago
hinkley•8mo ago
hinkley•8mo ago
But we all have stories of a friend whose machine was slow because they hit the button not understanding what it does. For them it did become the turbo button.
burnt-resistor•8mo ago
magicalhippo•8mo ago
Kept it on except for one ninja game which was unplayable on turbo, using fixed cycle count as delay mechanism. So all enemies and movements were crazy fast on turbo.
burnt-resistor•8mo ago
(The turbo button slowed the clock rate down for old games and some ISA cards that didn't like faster clock rates.)
coolcase•8mo ago