#41

That’s the approach I’ve gone for. I now subscribe to Gold Collagen Forte Ageless https://www.gold-collagen.com/uk/forte-ageless/

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#42

Testing for mtDNA is hard. Mitix do it for themselves. I have discussed with others doing it, but not got any progress. I think testing acid base balance may be an easier option, but has issues.

In the end i monitor function and watch hair follicles. .

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#43

With acid-base balance, do you mean an Arterial Blood Gas (ABG) Analysis to assess acid-base status, measuring parameters like pH, pCO2 and bicarbonate (HCO3−HCO3−​) in an arterial blood sample?

For funcion, is measuring VO2 max and lactid acid on a test bike the thing to do? Hair follicles - meaning monitoring hair density?

The ratio between lactate and pyruvate from blood is supposed to be a measure of mitochondrial health, but my ratio at less than 3;1, typically reflects efficient mitochondrial oxidative metabolism and will hardly be further reduced. . Instead, I assume improvements in mitochondrial health - which surely there is a scope for at my age despite a strict health regimen - would likely manifest in other ways, such as increased energy production (ATP)

#44

Yes that plus measuring serum krebs metabolites.

I think VO2 max is a good metric, I am not so sure about lactate.

I haven’t got a fully worked out proposal for measuring these things. However, there are papers which look at them which give some indications.

It is actually the ATP/O efficiency we are looking for which should be replicated in mitochondrial membrane potential.

However, this will vary from mitochondrion to mitochondrion. Hence the average can be measured in some way.

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#45

Thanks, John.

Do you think there is a decent chance that the results shown in that study will hold true for humans?

I have not seen anything about a good status of mitochondria in those with hyperprolinemia, although their high proline levels are admittedly chronic which is not good.

#46

I would/will add proline to my collagen, but a this time I would not add taurine to collagen. This since taurine and glycine act on the same receptor. (The Glycine receptor).

#47

Collagen is composed of proline, so no need to add it.

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#48

Yes, I know that Collagen consists of proline. But will the proline content in Collagen be enough to produce a meaningful effect?

According to the collagen I use, it consists of 12,5 % proline and 21,2 % Glycine. Those are big numbers. But if I take 15 gr of collagen, I will only get 1,9 gr of proline and 3,2 gr of Glycine.

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#49

Oh I see.
The actual amounts needed are hard to extrapolate from studies and also depend on rest of the diet.

Personally, there is not enough evidence to compel me to add another single amino acid to the stack.
It definitely reinforces my use of daily collagen.
THere are so many helpful amino acids like taurine, l-carnitine, l-glutamine, proline, lysine, etc that it sounds to look me like we should just eat more protein period, without adding more BCAAs which are m-tor activators and should be kept in check IMO.

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#50

If one wants to try the single dose mentioned in the article, PQQ 100 mg + AAKG, how long should they wait after taking PQQ before taking AAKG? Or should they be taken at the same time?

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#51

PQQ and AKG are taken together.

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#52

Hi everyone :wave: I’ve been struggeling with low energy for a few years now, so I really wanted to try Turnbuckles mito protocol to see if it might help with that. I started with a smaller dose 3 days ago: 500 mg CaAKG on an empty stomach, followed with 40 mg PQQ 20 minutes later. I felt very good and energetic the whole day.

However, my energy levels crashed 1 day later and stayed low since then (basically I’m super fatigued and exhausted for no reason). I’m not sure if the crash is even related to the protocol, but I’ll try again in a few days. This time, I’ll take 2g AAKG along with 100 mg PQQ, so no delay between the two.

#53

I suppose 30.- 40 grams would be even more likely to make progress. Is 10 - 20 grams a trade-off to limit risk of side-effect?

Could you expand on how many days a protocol would need to likely capture hoped for benefits for mitochondria?

#54

I don’t think we really have enough information to make such a judgment reliably. I keep proline on my experimental list, however, it is not a high priority although I have now found the proline I bought.

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#55

If I remember correctly, when the cycle of fission and fusion was being discussed, followers reported a crash/low energy at the fission stage, and a recovery at the fusion stage. After several (no typical number) cycles, the crashes stopped. Some took weeks or months to experience no crashes.

That is the reason I am doing the penultimate protocol of fission/fusion.

Mito1 and Mito2 were taken on alternating days. Each dose was taken in the evening and reps of dumbbell curls to failure counted first thing in the morning — five or six hours after dosing — using the same arm.

My hypothesis was that the number of reps would reflect mito damage. With mito fusion, enzymes are shared, thus ATP production and reps would be maximum. With fission, methylated (or otherwise damaged) mtDNA produce less ATP and reps would be minimum. The difference would reflect average damage, and if the treatment worked, the difference should decline. If all damage was removed, then the difference should go to zero.

Which in fact it did. See the plot below. The y-axis shows the reps and % difference, while the x-axis shows days. The curve labeled baseline is without any treatment, and likely reflects the normal intermediate situation with mito morphology in a dynamic state. It is stable at 16 reps. The upper fusion curve is relatively flat and higher than baseline as expected, while the lower fission curve is lower than baseline, but rises to meet the fusion curve after about two weeks, and stays there. Thus the percent difference goes to zero.

Results:
Improvement in running endurance, reduced hunger, and reduced need for hypertension medication.

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#56

At the fusion stage, one can either use GMS (glycerol monostearate) or DHM (dihydromyricetin).Turnbuckle reported elevated BP with GMS, and found out that DHM is equally effective, with no BP elevation. DHM also crosses the BBB (blood brain barrier).

#57

I personally cannot understand why fusion is better than mitophagy. Mitophagy gets rid of the inefficient mtDNA. Fusion merges the inefficient mtDNA with more efficient.

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#58

Background:

Previously I posted methods of cycling mitochondrial morphology to clean up defective mtDNA, which eliminated mutations via the PINK1/Parkin QC process. The normal QC process can detect mutated mtDNA genes during fission as all mito genes are critical and thus the mito membrane potential goes to zero if just one is defective. Greatly magnifying fission and fusion with supplements will aid that process. But there is another source of mitochondrial damage that isn’t so easily eliminated — epigenetic damage. Like nDNA, mtDNA also picks up aberrant methylation with age. This methylation degrades ATP production, but the QC process doesn’t catch it unless the problem is addressed at a critical time, like during biogenesis. If a mitochondrion with one loop of methylated mtDNA runs out of enzymes while involved with replication, then membrane potential may dip to zero and it will get labeled for recycling. Thanks to methylation, it won’t have as much enzyme reserves as other mitochondria, so it will be preferentially targeted. Also, biogenesis is the best time to demethylate mtDNA as methyltransferase can’t operate while there is only one strand.

Until recently, mtDNA wasn’t even known to have methylation, and researchers are still confused as to why it is there. Some speak of mtDNA hypermethylation like it is bad while normal methylation has some purpose.

See, for instance: Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility

I don’t agree. I say all mtDNA methylation is bad. Methylated mtDNA mooches enzymes off other mtDNA, and because they don’t produce as much ATP they don’t produce as much ROS, and thus have a survival advantage as they are less prone to mutation. Eventually the cell will become full of moochers and result in fatigue and many other problems of aging.

So I say get rid of them all, mutations and methylation alike.

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#59

It is certain that we are speaking in simplistic, understandable terms rather than what is really happening…but what I’ve read is that fission / fusion is happening all the time thing with certain conditions emphasizing one over the other just a bit. It is a process, and it is the process that matters not one piece of the process.

Fusion is where Mito join together to allow for damaged mito to isolate their damaged parts from their healthy parts. The damaged parts later get fissioned off into a separate units which will be eliminated (mitophagy).

Let me know if you understand it differently.

#60

I would need to track this back to original references. Without a histone the only epigenetic issue that matter are those that relate directly to the DNA. However, I have not seen reports on mtDNA methylation.

Hence I would be interested in back track this. I have a glance at the Hypermethlation paper and that needs some focussed attention.