As we were told during high school biology: cardiovascular muscle contains vast amounts of mitochondria as compared to other muscle types. Mitochondria are good. Therefore, more and stronger mitochondria = more efficient working muscle tissue.
One of my favorite professors holds a PhD in kinesiology (exercise physiology concentration) and wrote his dissertation on the mitochondria. As he stated many times in class: if you want to have a superhuman composition, acquire more mitochondria. he was always willing to bet his kids entire college tuition funds if you could show him a pill that would produce more mitochondria.
> Activation of Rev-ErbA-α by SR9009 in mice increases exercise capacity by increasing mitochondria counts in skeletal muscle.
> Some companies are selling SR9009 online for human use as a 'research chemical'.
> "The drug [alters] the circadian rhythm (in mice) and we would need to assume in humans – and we don't know if it is beneficial or detrimental at this point."
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It has "several issues that make it unsuitable for human use".
> Firstly, it has no oral bioavailability. I know the company selling this is indicating taking it orally is ok – but it doesn't even get into the blood.
> SR9009 has some functional groups that are known to have potential toxicology liabilities and it would never be developed as a drug.
> So bottom line – I would never recommend using this compound at this point. That being said – we are still working on improved compounds with one of the potential uses being sarcopenia – loss of muscle and strength due to aging.
Well, it definitely is a meme as defined by Dawkins[0]. In general, I would say that analogies and metaphors like this one have a huge impact on normal science, and are one of the main things that change during a paradigm shift. I recall a great example in how 150 years ago people thought of the body's physiology as analogous to a steam engine with downstream effects due to pressure building up, contrasted to how in today's computer age, we tend to think of physiology in terms of signal processing.
I agree, the imagery that we use in metaphor (in speech, visually, or in conception) influences how we think about things - and a popular analogy like that about the mitochondria is certainly a meme, a "cultural information transfer".
As you pointed out, a fairly recent meme is "the brain is the computer of the body", and maybe "the Internet is the brain of humanity".
The cells would consume more energy, so you'd need more food, so in conditions of food scarcity (i.e. 99% of our [pre]history) you would be at a severe disadvantage as your tribe would starve to death in conditions when more efficient homo sapiens would still survive.
There are other cell types that have a strongly increased amount of mitochondria like brown adipose tissue. They also don't have a "need" to perform some work constantly.
As with any cell function how much work mitochondria perform is highly regulated. Just because you have a lot of them doesn't mean you can't turn their function down.
Nadia Commenci was recruited as a gymnast at age five because she was too active and breaking the furniture at home. She made the first ever perfect 10 score in the Olympics. They didn't have a way to display it. It got displayed as 1.00 because they only had three spaces on the sign.
Her best friend became a professional ballerina.
I have heard that Chuck Norris does two workouts a day and if he skips one, he makes everyone around him crazy. If he does two per day, he's calm, cool and collected and fine to be around. If he doesn't, welp, he can't sit still and he can't control his mouth and he bounces off the walls and everyone can't stand him.
I also talked about the addiction process and mitochondrial function in a different comment.
> I have heard that Chuck Norris does two workouts a day and if he skips one, he makes everyone around him crazy. If he does two per day, he's calm, cool and collected and fine to be around. If he doesn't, welp, he can't sit still and he can't control his mouth and he bounces off the walls and everyone can't stand him.
this is a common theme among people who do lot's of sports. I did plenty of marathons, trail competitions in my time and a day without exercise felt like absolute agony mentally. There is probably also a psychological effect from missing the routine. Most sports addicts I know (including and especially body builders) have the problem of not giving their body enough recovery time between workouts causing them to actually perform less well, etc
I have a son that I put in gymnastics when he was a child. One of his teachers basically told us "Put him on Ritalin" because he never sat still in class. ADHD had already been ruled out, so this "Let's skip diagnostics and go straight to just drugging your kid for my convenience" attitude really pissed off my husband.
If he was exhausted enough, he occasionally sat still. So he was in gymnastics for a time and, when he was younger, I just made sure to take him to the park and stuff a lot so he could run around some every single day. Otherwise, there was no hope he would actually sleep.
> this is a common theme among people who do lot's of sports. I did plenty of marathons, trail competitions in my time and a day without exercise felt like absolute agony mentally.
And then along comes coronavirus, and the privation for exercise addicts while under quarantine is so much less than what many are experiencing, but it's real—and no-one takes "it's hard not to exercise" seriously.
Top endurance athletes do specifically targeted workouts which significantly increase their skeletal muscle mitochondria density. They don't appear to have trouble resting; rather the opposite.
Endurance athletes do not routinely exhaust themselves during workouts. Instead they work out to build mitochondria (among other goals). Hence the popularity of polarized training programs. Exhaustion impairs proper rest and recovery. Your suggestion is not consistent with what we see happening in humans.
They don't remain endurance athletes by skipping workouts for months on end. I've seen articles where some body builder got the flu, couldn't workout for a week or so and lost significant amounts of muscle mass, like 25 pounds.
You develop capacity like that, you use it or lose it.
And maybe I'm not making my point very well, but everything I've seen in life suggests such people do have a real need to workout regularly. It's not a "nice to have" for them. It's a "must have."
There was even a woman who was eventually diagnosed with a genetic disorder whose disorder had long been de facto managed by her very active lifestyle.
But I'm going to step away from this discussion. It's starting to look like a pointless pissing contest and that's not really my cup of tea.
Losing “water weight” is a thing. Boxers do it as part of their weight management before their weigh-ins. When I am well-hydrated I lose ~1.5 lbs of water weight just by sleeping (by weighing myself before bed and right when I wake up). If I take a piss it’s an even 2. And we lose a lot of body fluids when we have the flu.
That wouldn’t account for all 25lbs (which is a significant sum to be losing in a week — is that even factual,? Did this guy weigh 350 lbs lean?), but it could account for a good amount of it over the span of two weeks if he was really sick and also not eating well due to lack of appetite, diarrhea, sore throat, etc. How quickly did he get his weight back? Did he lose any significant amount of strength?
The flu is not the same as being out of the gym for a week. Although we do know that you will begin to lose incrementally more and more muscle mass the longer you’ve been out of the gym, being out of the gym for one week shouldn’t lead a bodybuilder to lose 25 lbs, and sometimes it’s even part of good training strategy to take a one week break from the gym to let the nervous system recover, which gets taxed just like the muscles do.
Src: I studied Biological Science at university
Also, during my histology course when we covered different muscle types, we discussed the topic of fatigue in cardiac tissue, but I remember being left with a feeling that we didn’t really know the underlying physiology yet (this would have been nearly a decade ago) but the main arguments were that cardiac muscle is not the same as skeletal muscle, whose differences can be seen under a microscope, and that the heart has enough time to recover when it’s not contracting.
Here’s a similar question — does the esophagus ever get tired? How about the diaphragm? Do you ever get tired of breathing?
I really don't remember the details and the original article may not have listed weight loss. It may have listed inches around his biceps lost.
I just remember it being hyped a bit concerning "yeah, he looks amazing -- but you can't take a break at all because when he had the flu, he saw crazy declines in a short period of time." I want to say a week, but that could be wrong.
I'm seriously bad with remembering names, titles, etc.
I also remember a friend who took up weight training after giving birth. She said she lost four inches around her waistline and only lost four pounds because muscle mass is generally heavier than other tissues.
I've had similar conversations with other women who were trying to lose weight or otherwise work on their physique. Some are downright disappointed by such results because they are looking for a specific number on the scale.
Sort of tangential: I knew a woman who quit smoking. Smoking suppresses the appetite and meets oral needs. People who quit often take up snacking as a substitute and their weight shoots up.
She said she would weigh herself and cry and her husband would basically talk her out of taking up smoking again because she was so upset at the weight gain.
Anyway, my mind organizes info its own way and I'm not always happy about it and it sometimes gets me into all kinds of social hot water because it sounds like crazy talk to other people. So this is probably not going to get better from here.
It isn't physically possible to lose 25 pounds of lean muscle mass in a few weeks. That's off by an order of magnitude, check the energy and mass balance calculation.
But frequent exercise is certainly a "miracle drug" in that it effectively prevents or treats a host of different medical and psychological conditions.
Edit: I will add that I am also, no doubt, basing it off of background knowledge about cell function. For example, mitochondria change and develop greater capacity to process X if you consume a lot of it, which is part of the addiction process and part of why withdrawal is a thing. If you consume a lot of, say, alcohol, you need to ramp down gradually so that the body can make changes at the cellular level to adjust to the lesser amount of alcohol and this is part of why cold turkey is so very hard and it is generally recommended that you taper off.
I used to ask smart people with PhDs and the like a lot of questions about cell function and read what I could get my hands on that could be followed by a lay person because I have a genetic disorder that impacts cell function.
Non-repetitive weight lifting wouldn't be a good example, but neither is anything in 10s of km.
Mitochondria produce ATP as energy. You can't store much¹ ATP, therefore mitochondria must be capable of producing ATP at your near peak output (say 10s average).
I'd look at anything with high >10s peak power (probably a bonus if it's aerobic). Many bodybuilding exercises would qualify.
¹ Lactic acid is a byproduct of ATP production, therefore ATP supplies surely last less, than what it takes to start producing lots of lactic acid.
Aren't mitochondria captive cells from early evolutionary times?
I googled and from nature.com
"Mitochondria and chloroplasts likely evolved from engulfed prokaryotes that once lived as independent organisms. At some point, a eukaryotic cell engulfed an aerobic prokaryote, which then formed an endosymbiotic relationship with the host eukaryote, gradually developing into a mitochondrion."
> If the heart is a muscle, why doesn't it get tired?
Because it's illogical to assume muscles fatigue. They physically don't get to the point where they can no longer operate -- under normal everyday use and exercise.
What does happen, that may seem like fatigue, is a gradual shifting of fuel sources by muscle cells depending on exertion levels.
Suffice to say, it goes like this:
- First: Creatine Phosphate is the first energy source in your muscles, the most powerful one, and the least plentiful. It's the first to go during exercise and is partly why you focus on 1-5 reps for strength-focused lifting (that's roughly how long it takes to get used up)
- Second: Glycogen in your muscles and liver. This is fairly plentiful, fairly powerful, and rapidly mobilizeable. After your creatine phosphate stores are emptied, glycogen takes over. This is still a very powerful fuel source, but its metabolism creates a negative feedback loop on itself. You can only sustain moderate exertion (see: sprinting or 8-15 reps moderate weight) for around 60-90 seconds, before glycogen is no longer easily accessible (note: accessible, not depleted. It's almost impossible to deplete in a single workout)
- Finally: Fat. Once you've exhausted glycogen, your body turns to fatty acid oxidation. This is the least powerful but most plentiful. In normal exercise you use a mix of fat and glycogen depending on how hard you exert yourself. Harder: more glycogen. Easier: more fat. If you want to know how it feels like to run on only fat: do a marathon -- then hit the wall. What you experience is literally the complete depletion of glycogen, and a transition into "low-power" mode as your body starts running on the only fuel source it has left: fat. You have months of this fuel source on your body, you won't run out. You can keep walking for days without having eaten anything or slept, but you won't be able to run at any pace that resembles a jog. I know, because I have.
What's the point of all this? It's to illustrate that muscle "exhaustion" is a misnomer. Muscle exhaustion is, in reality, a depletion of power-generating fuels leading to a state of minimal exertion.
Coincidentally, that's the mode the heart operates in 24/7.
Coincidentally, the heart has an asinine amount of mitochondria to fuel non-stop fatty acid oxidation.
The heart doesn't fatigue because it's not physically possible. It doesn't need creatine phosphate or glycogen (very very little) to pump blood. It's not a strenuous task.
An aside: if you had as much mitochondria in all your cells, as you do in your heart's, you would waste away.
Some anecdata but, I suffered from very bad muscle injuries from one summer in 2014. I skateboarded hard for two days in a row. Ran 3-ish miles on both days. Two days later I was exhausted but took two ibuprofen and I went to a beach with friends anyway. Where I skated hard at a park for a few hours, then swam, then ran. A day or so later, after not getting the best sleep, on an hour drive home, I pull both quads. The day after I had to call out for a week. I was exhausted and my obliques, core, quads, and arms were beyond sore. I laid around for most of the week.
Your muscles may not get "exhausted" but it seems like there must be some breakdown in the cells that outpace recovery at some point.
When they work, muscles break fibers. The more intensely you work out, the more they break. So you have to rest for them to be rebuilt (and more fit to the exercise), otherwise at some point they give in. The more frequently you train, the more they can withstand.
That seems unlikely given that if he had rhabdo he’d have felt bad enough to need to go to hospital. 20% death rate due to kidney failure is not to be sneezed at.
You can't really exert yourself to the point of a heart attack unless there is some other pre-existing condition like a congenital heart defect, arterial blockage, history of cocaine use, etc.
Then I guess the obvious question a non-physiologist would ask is, why don't all our muscles already have vast amounts of mitochondria? If it's that beneficial with no major downsides then surely evolution would have stumbled on that configuration already?
Because the trade-offs are not optimal for most people. Might require huge caloric budgets not available (until now). At present, energy efficiency is actually detrimental to reproduction for most people in first world countries, so it's conceivable if we wait another million years or something, our muscles might have a lot. Assuming not getting tired leads to reproductive success, of course.
For a vast amount of human history food has been much harder to obtain and less calorie-dense than it is today, so evolution has optimized for energy efficiency rather than raw power.
Significantly, and a large part of the reason why is energy efficiency. Humans have large brains that take a lot of calories to sustain, and because of their large brains didn't have nearly as strong evolutionary pressure to maintain musculature.
Probably the wrong way to look at it. They can exert greater force for shorter periods but the great apes have far worse endurance than humans. A chimp is about a third stronger than a human of equivalent weight but we can run marathons and they can’t. We have a higher proportion of slow twitch muscle fibres compared to fast twitch than the great apes.
Think of evolution as Uncle Fester from the Addams Family.
You never know quite what you'll find him working on, but every now and again, he'll have just the thing for the job.
But by and large, it's most likely something completely insane. Evolution has no intent. No direction. It's more a descriptive statement of an ongoing process than a end to which some force is constantly seeking.
not only energy expensive but free radicals do genetic damage, and a this requires the second budget for a set of enzymes to counteract the damages and scrub out FR's
Muscle cells don't replicate past early childhood development, they just get bigger and add more nuclei. So muscle cancers are extremely rare compared to cancers of other tissues.
each nucleus contains a full genomic content.
muscles are more of a "myosynsynctium" than a group of cells.
there are cohorts of cells that are more prone to becoming cancer due to thier developmental origins and the complement of developmental mechanisms that can be reactivated.
things such as cell adhesion, and cell migration through tissue dermal cells are good at this as they do these things over the course of development.
muscles are built where they will live so these features are inhibited somewhat more completely and harder to "switch on or off"
Neat, but why don't all the cells in our body do that? What's the trade-off that goes the other way for cells most likely to get cancer (prostate, breast, lungs, lymph nodes)?
As others pointed out, an increased output would not be sustainable long term within the normal body. The physiology behind action potential[1] and refractory period[2] explains how they compliment each other to make sure our system function properly and effective.
Not unless having vast amounts of mitochondria is a competitive survival/reproductive advantage favoring natural selection of individuals in their environments
He would have lost his sons college thition then. Mitochondrial _inhibition_ is actually more correlated with longevity than the other way around.
If more mitochondria meant more efficient working muscle tissue, then that's what we would have evolved, there's always a compromise. Are you sure you can keep the same power output for a given mass and volume of muscle if you keep increasing mitochondrial numbers? Even the reddit answer clearly says that the heart muscle is rate limited by oxygenation (they have more mitochondria but are also highly vascularized to power the mitochondria). More mitochondria===more power doesn't mean it's better for us, physiology is rarely that simple.
Specifically it is due to reproductive defects in mitochondrial dna as one ages. Anti-aging researcher Aubrey de Gray has a talk on this specific issue:
But evolution didn't decide on the structure and behavior of our throw-away-cup bodies in order to make our puny minds sitting on top our puny brains happy.
For better or for worse, in humans (we are not turtles, for example, they have their own success strategy), AVERAGE 2nd generation reproductive success is the measure of our existence. The collection of strategies to maximize that are different for human men and human women. But aligned. On average. 2nd-generation reproductive success is our "purpose" in a universe made mostly out of hydrogen. Nothing more - nothing less.
One of my favorite professors holds a PhD in kinesiology (exercise physiology concentration) and wrote his dissertation on the mitochondria. As he stated many times in class: if you want to have a superhuman composition, acquire more mitochondria. he was always willing to bet his kids entire college tuition funds if you could show him a pill that would produce more mitochondria.