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The following was posted by Dave J on the forum and is reproduced here by his permission/encouragement.

LEF is hyping PQQ as the new hot anti-aging "vitamin", and of course other manufacturers of nutritional supplements have rapidly followed suit. The salespitch looks pretty good. Maybe most of us get enough in our diet anyhow, but that wouldn't make for very good marketing press. 

The thing that's bothered me the whole time is that new mitochondria don't appear out of thin air, they (like their bacterial ancestors)reproduce by fission. 

So if you've got a mitochondrion that's a bit worn out but still functioning, and it's possibly even acquired some genetic defects along the way, what do you get if it fissions? Two new mitochondria neither of which is functional? 

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I'll now almost contradict myself. 

Mitochondria do appear out of thin air. A bunch of chromosomes encode 'em from a single fertilized egg, right?

Wrong. The first mitochondria come from the egg only. 

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Therefore the problem of mitochondrial aging is this: where can we find good mitochondria from which to make copies by fission?

Is this a question to which stem cells have the answer? 

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Stem cell research has a long history of falling on its face badly. It started with the hope that you could just take some stem cells, pull the right trigger, and get a new whatever tissue or organ you wanted. 

In the specific case of motor neuron disease, the original idea was that the primary disease process was death of motor neurons, and that stem cells would grow new motor neurons. In the case of classic ALS, to restore leg function that would require two new neurons nearly a meter long each, knowing where they needed to go to meet up, and (given that little problem of lateral sclerosis) find some way to create new spinal ganglia that incorporate sensory neurons as well. That's just about like Google expecting their self-driving car to make a successful round trip to Uranus. Google's smart enough not to put that objective on their agenda. 

Then the idea shifted to maybe the shorter and less complex paths involved in bulbar were possible. There were a few reports of limited success, but doubts have been raised that the favorable therapeutic reports had anything to do with replacing dead motor neurons with new ones. 

Nowadays the mainstream of the leading edge seems to be that stem cells secrete substances favorable to neuron survival. This is in agreement with an emerging realization that in "ALS" type motor neuron disease, the development of symptoms is not driven by death of neurons, it's driven by failure of neuron functionality, and that actual neuron death is a considerably downstream event. Partial recovery of the patient is possible if the alive but nonfunctional neuron can be restored to function. 

It is widely accepted these days that neuron death is driven by the death of motor neuron mitochondria. The failing mitochondrion releases molecules (pro-apoptotic caspases) that signal glial cells to target the neuron involved for destruction ("neuroinflammation") since the neuron no longer works and should be gotten out of the way. (Too bad that adjacent neurons catch fallout, accelerating the neurodegenerative cascade. It's important to treat ALS early and aggressively!

Motor neurons are almost unique in that the body cannot replace them past some point in embryonic development, because the information on how to get from Point A to Point B has gotten out of range. This is one reason why research based on anything resembling embryonic conditions (for example in vitro) usually leads to completely wrong conclusions regarding therapeutic potential. The problem faced in embryonic development with all the rapid multiplication of cells going on, is how to recognize and get rid of motor neurons that are failing to get connected right!

Now that we're adults, we have this problem: the whole biological pile we've got now is based on general principles that for the sake of simplicity don't do a good job of recognizing that motor neurons are a special case that should be treated gently. And,(like it or not) Darwin's Law dictates that we really have to sacrifice our butts and get the hell out of the way so that the next generation can do their jobs without us getting in the way. When you look at the whole thing from an evolutionary perspective, the surprising thing is that motor neuron disease isn't more common. 

Looking into it more deeply from an evolutionary perspective, the mitochondrion is a specialized organelle the job of which hasn't changed much since the Precambrian. It's protected from getting screwed up by inheritance through the egg (maternal line), exempting it from the rapid evolution (and vast array of genetic mistakes) produced by sexual reproduction. What I just described isn't 100% true, but it's a very useful explanation. Without the bacterial contribution to genome but lurking outside the path of sexual reproduction, no animals: animation requires energy, and it was a bacterium that provided the key that unlocked efficient high-intensity redox.

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A supposed therapeutic that incites a severely stressed mitochondrion to fission, will likely kill the mitochondrion and accelerate the disease process. That's why I'm wary of PQQ as a motor neuron disease therapeutic. Whaddayawanna bet that some antibiotics kill off bacterial infections in just this way-- by forcing fission under conditions that are unfavorable to fission? 

On the other hand, suppose that stem cells could either secrete factors that restore stressed motor neuron mitochondria to health, or better yet inject newfangled progenitor mitochondria into motor neurons? Can stem cells do such things? I don't know, but at least now we're talking about actually curing a key aspect of motor neuron disease, and not just propping up a failing system for a few more weeks or months.