2284 replies to this topic

[aribadabar]

I've done 15 cycles of the original protocol, so it will be interesting to see how what this new version contributes.

 

Yes, hopefully Turnbuckle can suggest if come cycling between the two versions of the protocol is better or start with original and then switch to the latest and then stay on it or going straight to the latest ( skipping the original altogether) is OK?

[mike20g]

Just finished reading 59 pages of forum. Very interesting. I am middle-aged, not sure how many broken mitochondria I have, but guess I will see it quickly once I start the process. Any advice for the beginner would be greatly appreciated.

 

I would also like to try "Stem cell self-renewal with C60" after I do Mito protocol and after I take a baseline age test (by the way in Post 1 " C60 dosing and an epigenetic theory of action" , I would point to an embedded link "Baati rat study" - it needs correction, at this time it points to "thematic adult website" .)

 

Question that I had is if anyone knows if Mito protocol showed any improvements in hypothyroid patients? I would think it may be very beneficial for them. From what I heard from endocrinology doctors is that hypothyroidism is considered untreatable, but I have observed very good results with using herbs from traditional Chinese medicine. Mito protocol may be very beneficial as well. 

 

[userCK]

Looks like many of us can not find pure un-buffered, fast digesting AKG, neither in the US nor in Europe. Is there an alternative for it @Turnbuckle? How about if we took AAKG couple of hours before taking PQQ and Niacinmide and d-Ribose?

Edited by userCK, 20 February 2021 - 08:38 AM.

[PAMPAGUY]

Looks like many of us can not find pure un-buffered, fast digesting AKG, neither in the US nor in Europe. Is there an alternative for it @Turnbuckle? How about if we took AAKG couple of hours before taking PQQ and Niacinmide and d-Ribose?

https://www.evitamin...man-labs-104882, located in Michigan, I believe.  I ordered and paid to ship to Spain

[Turnbuckle]

For those asking:

 

The old protocol is no longer needed. With the new protocol, mutated mtDNA will be removed first just as in the old one, as their membrane potential will zero out first, before the epimutated. It was my expectation that if epimutations were not eliminated, the experimental curves might never intersect. But they did.

 

Results will vary according to your damage level. If you have a lot of damage, it could take a lot longer. If you have none, you will see no difference between fission and fusion. To know when you're done, keeping track of it numerically will work better than vague subjective feelings.

 

As for AKG, I used the simplesa liquid for the greatest bioavailability. You could use powder too, of course, though I suggest dissolving it first. For the experiment I left the PQQ in caps and took everything else in water. Taking a few grams of AAKG an hour before would also be an option. I was looking for a unitary dose, but what's the worst that could happen if you don't get that part right? It just won't work as well, I expect. And if you are monitoring your progress numerically, you will see it.

Edited by Turnbuckle, 20 February 2021 - 01:38 PM.

[kurt9]

I am currently chelating with ALA (for Mercury and other metals). I finish this by June. I will try this new Mitochondrial fission/fusion routine once I finish chelation. 

 

I am not nearly "geriatric" enough to do the senolytics with stem cell replacement routine. But its nice to know that it is an option for whenever I do need it as some point in the future.

[userCK]

For those asking:

 

The old protocol is no longer needed. With the new protocol, mutated mtDNA will be removed first just as in the old one, as their membrane potential will zero out first, before the epimutated. It was my expectation that if epimutations were not eliminated, the experimental curves might never intersect. But they did.

 

Results will vary according to your damage level. If you have a lot of damage, it could take a lot longer. If you have none, you will see no difference between fission and fusion. To know when you're done, keeping track of it numerically will work better than vague subjective feelings.

 

As for AKG, I used the simplesa liquid for the greatest bioavailability. You could use powder too, of course, though I suggest dissolving it first. For the experiment I left the PQQ in caps and took everything else in water. Taking a few grams of AAKG an hour before would also be an option. I was looking for a unitary dose, but what's the worst that could happen if you don't get that part right? It just won't work as well, I expect. And if you are monitoring your progress numerically, you will see it.

 

Thanks!

[Advocatus Diaboli]

re: Simplesa

 

Do a Google Earth (or similar) "street view" search on Simplesa's address to see the businesses at their 4850 SW 72nd Avenue, Miami, FL 33155 address.

 

Also, do a tineye search on Simplesa's building .png given on this page. Note the transmogrification evident between their building image on their website, and the building that appears on Google Earth.

 

In addition, click the certificate-of-analysis link, found here, in order to not see a certificate of analysis.

 

caveat emptor

[PAMPAGUY]

For those asking:

 

The old protocol is no longer needed. With the new protocol, mutated mtDNA will be removed first just as in the old one, as their membrane potential will zero out first, before the epimutated. It was my expectation that if epimutations were not eliminated, the experimental curves might never intersect. But they did.

 

Results will vary according to your damage level. If you have a lot of damage, it could take a lot longer. If you have none, you will see no difference between fission and fusion. To know when you're done, keeping track of it numerically will work better than vague subjective feelings.

 

As for AKG, I used the simplesa liquid for the greatest bioavailability. You could use powder too, of course, though I suggest dissolving it first. For the experiment I left the PQQ in caps and took everything else in water. Taking a few grams of AAKG an hour before would also be an option. I was looking for a unitary dose, but what's the worst that could happen if you don't get that part right? It just won't work as well, I expect. And if you are monitoring your progress numerically, you will see it.

Turnbuckle, I have a known supplier here in Spain that sells me 50mg. PQQ.  Would it hurt the protocol to take 50 mg. vs 20 mg.?

[yz69]

if you follow the google map steet view, you will find that the sign on the building 4850 SW 72nd Ave is actually  "Wilma Schumann" which is "Wilma Schumann Skin Care". A little further search you will find "Simplesa" and "Wilma Schumann" share the same owner.

[Advocatus Diaboli]

re: post 1780

 

Yeah, yz69, Pedro has had 10 or so companies. As an internet mountebank, I suspect he has hit the jackpot with this latest venture of his. He is a slubberdegullion preying on poor souls with ALS, Parkinsons, and other neurodegenerative diseases. If you look in the Simplesa website, you'll find some CoA's (certificates of analysis--for those unfamiliar with the abbrev.) that are a complete joke.

 

For those who didn't drop the "Simplesa building" image into tineye, here's what you get.

 

 

 

[PAMPAGUY]

For those asking:

 

The old protocol is no longer needed. With the new protocol, mutated mtDNA will be removed first just as in the old one, as their membrane potential will zero out first, before the epimutated. It was my expectation that if epimutations were not eliminated, the experimental curves might never intersect. But they did.

 

Results will vary according to your damage level. If you have a lot of damage, it could take a lot longer. If you have none, you will see no difference between fission and fusion. To know when you're done, keeping track of it numerically will work better than vague subjective feelings.

 

As for AKG, I used the simplesa liquid for the greatest bioavailability. You could use powder too, of course, though I suggest dissolving it first. For the experiment I left the PQQ in caps and took everything else in water. Taking a few grams of AAKG an hour before would also be an option. I was looking for a unitary dose, but what's the worst that could happen if you don't get that part right? It just won't work as well, I expect. And if you are monitoring your progress numerically, you will see it.

What is the relationship between this NAD enhancing protocol and Cellular Senescence?  Not sure, if I understand it, but important to know.  Thanks

[nadaepeu]

Dear Turnbuckle,

 

do you think astaxanthin can be a useful addition to the fission part of the protocol?

 

Based on https://www.research...al_fission#pf11, astaxanthin significantly decreased the ratio of fused mitochondria/fissional mitochondria in the TGF-b1-activated A549 and MRC-5 cells

[sub7]

Hi Turnbuckle,

 

I have started using Red Light Therapy to accelerate recovery after workouts. The literature on Red Light Therapy specifically and Photobiomodulation in general (Photobiomodulation being the broader term that encompasses all types of light therapy using other spectrums of light such as blue) is absolutely enormous. 

Now when we shine red light on tissues -as you have also explained in one of your prior threads about using red light to accelerate fat loss- it will penetrate the superficial tissues of the skin and reach essentially all tissues. Red light is absorbed by cytochrome oxidase and kicks mitochondria into high gear; as long as the mitochondria is functional it will produce more ATP after exposure to red light. According to your thesis in this thread, doing this repeatedly should increase the accumulation of damaged mitochondria, no? And this would accelerate aging, would it not?

 

Now, I am not going to tell anyone that red light will reverse aging and I am certainly no expert on it. However, there are around 7,000 papers on Photobiomodulation and I just about drove myself mad reading abstracts of very many and full texts of some. Long term use of red light therapy appears to be very beneficial and it appears very unlikely that its use would accelerate aging. This thought occurred to me after I was done reading said papers or else I would have gone over them with an eye towards "effect of red light on mitochondrial quality" which I did not do. But again, looking back at all that I have read, even aggressive and long term use of red light does not accelerate aging. Many Alzheimer and Parkinson patients are deriving enormous benefits from it and some have been using it for a very long time now with extremely impressive results.

 

Does the above prove that red light does not adversely impact mitochondria quality? No it does not. While rather a far-fetched idea, it could be that red light reduces mitochondria quality a little bit, while improving tissue function in various other ways and the net result is positive. But that appears a little unlikely.

I would be most glad to hear your valued opinion. 

[ortcloud]

For those asking:

 

The old protocol is no longer needed. With the new protocol, mutated mtDNA will be removed first just as in the old one, as their membrane potential will zero out first, before the epimutated. It was my expectation that if epimutations were not eliminated, the experimental curves might never intersect. But they did.

 

@Turnbuckle

 

Can we use Urolthin A instead?

 

https://www.nature.c...467-017-00525-4

 

This article talks about urolithin mitophagy, fission, fussion, exercise capacity, longevity.

 

"However, the relevant autophagic cargo in the context of aging remains elusive. Mitochondrial autophagy (mitophagy) is a type of cargo-specific autophagy^{6, 7}, which mediates the removal of dysfunctional mitochondria. The molecular mechanisms of mitophagy have been elucidated in some detail in recent years⁸. Upon loss of inner mitochondrial membrane potential, PINK1, a mitochondrial kinase, is selectively stabilized on the surface of the dysfunctional mitochondrion, leading to the recruitment of the E3 ubiquitin ligase Parkin⁹. Upon mitochondrial recruitment, Parkin ubiquitinates mitochondrial outer membrane proteins^{10,11,12,13,14} and induces the autophagic elimination of the dysfunctional mitochondrion^6,7,8.

Recent studies in mammals, including humans, have reported an age-related decline in mitophagy^{15, 16}. Moreover, impairment of mitophagy recapitulates the age-related accumulation of mitochondria in Caenorhabditis elegans ¹⁷. These findings suggest that the mitophagy pathway may represent a therapeutic target to counteract aging. Consistent with this idea, overexpression of Parkin delays the onset of molecular markers of aging and prolongs lifespan in Drosophila ¹⁸. Furthermore, dietary urolithin A (UA) treatment induces mitophagy, prevents the age-related accumulation of dysfunctional mitochondria and prolongs C. elegans lifespan¹⁹. UA treatment also improves exercise capacity in rodent models of age-related decline of muscle function¹⁹. Together, these findings support the idea that impaired mitophagy is a significant underlying factor in the accumulation of dysfunctional mitochondria in aged animals contributing to organismal health decline and mortality. However, a major unanswered question remains: why does mitophagy decline in aged animals?

Mitochondrial dynamics (fission and fusion) and mitophagy are closely related^{7, 8, 20, 21}. Mitochondrial fission and fusion processes are both mediated by large guanosine triphosphatases (GTPases) in the dynamin family^{22, 23}. Mitofusin (Mfn) proteins mediate fusion of the mitochondrial outer membrane, while mitochondrial fission, conversely, requires Dynamin-related protein 1 (Drp1)^{22, 24}. Several studies indicate that an important event preceding mitophagy is the Parkin-mediated turnover of Mfn leading to a shift in the balance of mitochondrial dynamics toward decreased fusion/increased fission^{7, 20}. In yeast, the mitochondrial fission protein, Dnm1, homologous to Drp1, is required for certain forms of mitophagy^25,26,27. Together, these findings support the model that mitochondrial fission can promote the segregation of damaged mitochondria and facilitate their clearance by mitophagy^{7, 11, 12, 28, 29}. Critically, however, the interplay between mitochondrial dynamics and mitophagy during aging remains poorly understood.

The anti-aging effects of Parkin overexpression in Drosophila ¹⁸ and UA treatment in C. elegans ¹⁹ are both associated with an increase in mitochondrial fission. Critically, however, the question of whether an increase in mitochondrial fission alone is sufficient to prolong lifespan and/or improve mitochondrial function in an aged animal has not been addressed. Here, we show that inducing Drp1-mediated mitochondrial fission, in midlife, increases lifespan and improves multiple markers of health in aged Drosophila. Remarkably, we show that a transient induction of Drp1, for 7 days, in midlife is sufficient to prolong lifespan. Studying aging flight muscle, we find that a midlife shift toward a more elongated, less circular mitochondrial morphology is linked to the accumulation of dysfunctional mitochondria. Short-term, midlife Drp1 induction restores mitochondrial morphology to a youthful state, improves mitochondrial respiratory function and reduces mitochondrial reactive oxygen species (ROS) levels. Importantly, midlife Drp1 induction facilitates mitophagy and improves proteostasis in aged flies. Finally, we show that disruption of Atg1, a core autophagy gene, inhibits the anti-aging, prolongevity effects of midlife Drp1 induction. Our findings indicate that transient, midlife interventions that promote mitochondrial fission could delay the onset of frailty and mortality in aging mammals"

[Turnbuckle]

If anyone wants to try something different, by all means try it and report back. 

[stephen_b]

Anecdotal report. I did the original mitochondrial protocol for 15 cycles. I got to the point where the niacinamide/d-ribose combination had no subjective effect on me.

 

I have done one fusion and one fission cycle using the updated protocol. I experienced a strong reaction to the fission day (the same low energy I had at the start of the original protocol), so I guess there is some demethylation needed there.

 

The gram of GMS on the fusion day brought my blood pressure up to about 137/80. I can't say that my endurance on a 4 mile run the next day was any better. I'll do some more cycles and continue to monitor.

[muntjac]

I've taken the GMS and PQQ and found it more effective than stearic acid, sulforaphane, PQQ, and leucine. The old protocol had diminishing effects around the fourth cycle for me, they're now recurring. This brings me to a topic which has not been discussed much: what are the psychological effects of this protocol?

 

During the first two cycles of the old protocol, on fusion days, I experienced loose associations while falling asleep, and hypomania during the day. I did not suspect a link with the protocol at the time, now that it's recurred I did a literature search and found several papers on the role of mitochondria in psychiatric conditions.

 

Neurobiological basis of bipolar disorder: Mitochondrial dysfunction hypothesis and beyond

Novel Complex Interactions between Mitochondrial and Nuclear DNA in Schizophrenia and Bipolar Disorder

Mitochondrial dysfunction and pathology in bipolar disorder and schizophrenia

Mitochondrial Involvement in Mental Disorders: Energy Metabolism and Genetic and Environmental Factors

 

I'd suggest caution for those with a history of mania, this new protocol might be too effective to start out with.

[Turnbuckle]

I've taken the GMS and PQQ and found it more effective than stearic acid, sulforaphane, PQQ, and leucine. The old protocol had diminishing effects around the fourth cycle for me, they're now recurring. This brings me to a topic which has not been discussed much: what are the psychological effects of this protocol?

 

During the first two cycles of the old protocol, on fusion days, I experienced loose associations while falling asleep, and hypomania during the day. I did not suspect a link with the protocol at the time, now that it's recurred I did a literature search and found several papers on the role of mitochondria in psychiatric conditions.

 

Neurobiological basis of bipolar disorder: Mitochondrial dysfunction hypothesis and beyond

Novel Complex Interactions between Mitochondrial and Nuclear DNA in Schizophrenia and Bipolar Disorder

Mitochondrial dysfunction and pathology in bipolar disorder and schizophrenia

Mitochondrial Involvement in Mental Disorders: Energy Metabolism and Genetic and Environmental Factors

 

I'd suggest caution for those with a history of mania, this new protocol might be too effective to start out with.

 

 

Are you using the disodium salt of PQQ? If so and that proves a problem for anyone, they might switch to regular PQQ, which supposedly has a harder time crossing the BBB. 

[sub7]

Anecdotal report. I did the original mitochondrial protocol for 15 cycles.....

This a a very large number of cycles. Have you noticed any significant anti-aging / rejuvenation effects that you believe will be relatively long lasting -ı.e. effects that appear likely to continue at least for a while, even if you were to do no more cycles from here on?

 

[Phoebus]

Okay so what is the latest protocol then? 

 

which post should I read? thanks! 

[aribadabar]

Okay so what is the latest protocol then? 

 

which post should I read? thanks! 

 

Post #1739

[Danniel]

Maybe each protocol should get its own thread. The previous protocols should be closed with a link to the upgrade or to Turnbuckle's profile where he has  updated links to the newest versions.

[Turnbuckle]

[15 cycles] This a a very large number of cycles. 

 

 

 

How many cycles you need with the original protocol will  depend on your initial level of damage. If you look at Fig. 1 (A) of the second paper cited in the OP, you will see that cells cultured continuously with 5 mM NAM lost 20% of their mito mass in 24 hours, after which the loss rate much declined. This is a much higher NAM concentration than the protocol will create. How much mitochondrial mass is lost per cycle is speculative, but let's optimistically say it's 10%, and let's say you have 90% initial damage and that the PINK1/Parkin process is perfect, only getting rid of mutated mitochondria. So you lose 10% mitochondria in the first 24 hours, then increase the total back to 100% with PQQ. Since both good and bad mitochondria are increased by the same factor, you have now increased your initial good mitochondria to (10% / .9), or 11.1%. If you work this out on a spreadsheet, you will see that it takes 23 cycles to eliminate all mutated mitochondria. The actual number of cycles is very sensitive to the initial load. If you started with 75% damage, it would take you 15 cycles. If you started with 10%, it would take one cycle.

 

You may think 90% damage is very high and that you couldn't survive with that much, but it's not as bad as it seems. There are 37 genes in mtDNA, and every one of thousands of mtDNA in a cell could have one of those genes randomly mutated, and yet the cell get along with only a slight to moderate decline due to enzyme sharing with other mtDNA. If every one is genetically damaged, however, there is no coming back. With 100% epigenetic damage, it can come back, at least with the new protocol.

 

 

Edited by Turnbuckle, 25 February 2021 - 12:57 PM.

[Aman]

How many days of the mito1 and mito2 do you consider 1 cycle?

[userCK]

How many days of the mito1 and mito2 do you consider 1 cycle?

Aman. 1 cycle = Mito 1 + Mito 2. So, you're doing 1 cycle every 2 days.

[sub7]

How many cycles you need with the original protocol will  depend on your initial level of damage. If you look at Fig. 1 (A) of the second paper cited in the OP, you will see that cells cultured continuously with 5 mM NAM lost 20% of their mito mass in 24 hours, after which the loss rate much declined. This is a much higher NAM concentration than the protocol will create. How much mitochondrial mass is lost per cycle is speculative, but let's optimistically say it's 10%, and let's say you have 90% initial damage and that the PINK1/Parkin process is perfect, only getting rid of mutated mitochondria. So you lose 10% mitochondria in the first 24 hours, then increase the total back to 100% with PQQ. Since both good and bad mitochondria are increased by the same factor, you have now increased your initial good mitochondria to (10% / .9), or 11.1%. If you work this out on a spreadsheet, you will see that it takes 23 cycles to eliminate all mutated mitochondria. The actual number of cycles is very sensitive to the initial load. If you started with 75% damage, it would take you 15 cycles. If you started with 10%, it would take one cycle.

 

You may think 90% damage is very high and that you couldn't survive with that much, but it's not as bad as it seems. There are 37 genes in mtDNA, and every one of thousands of mtDNA in a cell could have one of those genes randomly mutated, and yet the cell get along with only a slight to moderate decline due to enzyme sharing with other mtDNA. If every one is genetically damaged, however, there is no coming back. With 100% epigenetic damage, it can come back, at least with the new protocol.

 

I must humbly and respectfully submit that the above is so wildly speculative that it cannot be used as the basis of any analysis at all, let alone actual, implementable treatment protocol. There are so many numerical assumptions as well as such an extreme assumption of repeatability as well as linearity that the above is just wholly unusable. 

 

Instead of this sort of theoretical approach, it would be much more helpful to hear the experiences of the poster who did the very many cycles. 

Again, your work is very much appreciated and your contributions are undeniable. The above though is not useful and carries the paternal to be extraordinarily misleading. 

[Turnbuckle]

I must humbly and respectfully submit that the above is so wildly speculative that it cannot be used as the basis of any analysis at all, let alone actual, implementable treatment protocol. There are so many numerical assumptions as well as such an extreme assumption of repeatability as well as linearity that the above is just wholly unusable. 

 

Instead of this sort of theoretical approach, it would be much more helpful to hear the experiences of the poster who did the very many cycles. 

Again, your work is very much appreciated and your contributions are undeniable. The above though is not useful and carries the paternal to be extraordinarily misleading. 

 

 

The numerical assumptions are merely a way of showing that it can take many cycles. Do you have any arguments with the following?

 

That mitochondrial damage builds up with time in spite of cellular QC and can contribute to disease and aging.

That ATP output is reduced by mtDNA mutations and methylation.

That the natural process of fission/fusion is used to eliminate mutated mtDNA by the PINK1/Parkin process.

That the natural process can be enhanced by forcing fission/fusion in a cyclic manner.

That the capacity for eliminating mutated mtDNA via mitophagy in a singe cycle is limited by lysosomal capacity.

That methylated mtDNA cannot be removed in this fashion as the membrane potential does not go to zero during fission.*

That methylated mtDNA can be reduced during replication by exposure to TET enzymes (demethylase).*

That during fusion, biogenesis does not distinguish between damaged and undamaged mtDNA. Thus both are replicated at the same rate. 

 

*Not relevant to the original protocol.

 

So then the variables are --

 

The initial level of damage, which will vary widely between individuals, and even in the cells and organs of one individual (and will vary in damage type as well).

The actual value of lysosomal capacity (which will likely vary among individuals), and the fraction of it used per cycle with a given level of NAM.

 

I showed experimental results of a cyclic treatment in post 1739, and I've reproduced that here. It only took 7 cycles this time (compared to an expected 8 by the argument I made in post 1794 just above), but I had already used the previous protocol some years ago. And that time it took months, as my mitochondria had been severely damaged by statin use, and even after years I had only partially recovered via natural QC. The previous protocol wasn't efficient, but I expect the new one would still have taken rather more than 7 cycles.

 

You speak of assumptions, but you told user stephen_b that 15 cycles was "a very large number of cycles." What was your basis for that statement?

Attached Files

•  Mito trial.png   476.47KB   0 downloads

Edited by Turnbuckle, 26 February 2021 - 12:07 PM.

[sub7]

Thank you for the answer Turnbuckle. Let me try and briefly respond. 

 

Please see the parts from your messages that I bolded (especially what I underlined):

How many cycles you need with the original protocol will  depend on your initial level of damage. If you look at Fig. 1 (A) of the second paper cited in the OP, you will see that cells cultured continuously with 5 mM NAM lost 20% of their mito mass in 24 hours, after which the loss rate much declined. This is a much higher NAM concentration than the protocol will create. How much mitochondrial mass is lost per cycle is speculative, but let's optimistically say it's 10%, and let's say you have 90% initial damage and that the PINK1/Parkin process is perfect, only getting rid of mutated mitochondria.

...

 If you work this out on a spreadsheet, you will see that it takes 23 cycles to eliminate all mutated mitochondria.  

 

Where do we get the 10% from? Absolutely totally pulled out of thin air. As someone deeply familiar with non-linear, complex systems, I have repeatedly observed that such systems have several unpredictable "kinks" and waves in the dose-response relationship graphs and these sorts of exercises, where we make estimates as you do, tend to be wildly inaccurate. I have operated in exactly this sort of fashion myself when dealing with complex systems and made exactly these sorts of "best effort" or "optimistic" or "pessimistic" assumptions and have simply walked away with the impression that these approaches tend to be far more often very wrong than to be even remotely right.

 

Just to demonstrate my argument with a totally hypothetical example: It could very well be that increasing the concentration of the "trigger" by 4.8 fold (a random number to demonstrate a principle) above baseline may result in 20% reduction in defective mitochondria, while increasing the same substance by 2.4 fold in the same tissue may eliminate almost no defective mitochondria at all. 

The far bigger assumption is that as we repeat this over and over again, we will attain the same result despite dramatically declining number of defective mitochondria. Again, seems very unlikely. Based on what? based on nothing concrete; based only on my observations of biological systems.... just a personal opinion of someone who has no recognized degree or published work in the field. I only would like to state that biological systems almost always present roadblocks as you repeat the same intervention over and over. I would very much expect -again based on no concrete data whatsoever- that possibly the various defective mitochondria will exhibit varying degrees of resistance to elimination/clearance, making each round less effective at some point and then almost completely ineffective at a later stage at some point. To continue to be equally successful in removing them at each pass appears very likely.

 

I showed experimental results of a cyclic treatment in post 1739...

You did not. To attach the term "experimental results" to what you have presented just demonstrates a totally unwarranted degree of confidence in your casual, personal observations. My passion for biology comes from my involvement in athletics. I have been around very ambitious athletes for a very long time. People (referring to not you or anyone on this forum, but making a general statement) live in a fantasy world and are under the impression that simple interventions exist to boost endurance or other athletic outcomes in a short amount of time -some of such interventions being legal and some banned in international sports. The reality is that boosting endurance with any sort of intervention -except of course specific exercise regimens- is extremely hard. If only you guys saw how little benefit such famous doping substances as EPO or cortisol provide, you'd be shocked (strength output BTW is a little different and can be elevated relatively more easily in the short term -albeit the results will likely not be long-lasting).

The results that you keep posting in this as well as other threads are so outrageous that they are simply not credible in the least and erode almost all credibility. Increasing endurance measurably with just a few cycles of the above??? People commenting that you actually look younger after 2 weeks of something??? In another thread regarding the use of red light, you posting that with the use a very weak light source, immediately feeling a reduction in hunger and then seeing dramatically accelerated fat loss on top of that? These claims are so outrageous that they are simply impossible to take seriously, thus also casting an unfavorable light on the rest of the discussion. 

 

You speak of assumptions, but you told user stephen_b that 15 cycles was "a very large number of cycles." What was your basis for that statement?

 

True, simply reading my previous comment, one can be left feeling that I too am making arbitrary assumptions about how quickly these interventions should or should not work. Let me rephrase my earlier question to stephen_b as follows. This will far better illustrate my position:

Stephen,

Throughout this thread, it appears that some people are seeing some kind of perceivable/observable results from these cycles after far fewer than 15 rounds; at least, that has been my impression thus far. If someone did the cycle 15 times, I would be inclined to think that the person has felt something along the way, thus continuing to stay motivated to carry on. Having read the user feedback on this thread, had I done 10 cycles without observing any benefit, I would perhaps have stopped the experiment as I would have concluded that "if this was going to work, it would have worked by now."

...................................................

 

With all that being said, you may then ask "well, then get the heck out of this thread; why are you still reading this?"
I am reading this, because you have an absolutely astounding degree of commitment to this cause. You dig out information and present it generously here. This much valuable information one would have to spend months, if not years to compile. The depth and breadth of information here just boggles the mind. It is merely some of the conclusions you draw that I have issues with.

If this is something that you don't mind answering in broad and vague terms, where does such dedication and attention to detail come from -as in what is your original profession / background? Because lemme tell ya, if I can serially produce a hundred Trunbuckles and put them to good use, I am sure we can land a spaceship on a planet at the far end of the milky way in a decade. 

 

[Turnbuckle]

 

 

Where do we get the 10% from? Absolutely totally pulled out of thin air.

 

 

Those researchers saw 20% with a continuous NAM molarity that would take 5-10 times as much oral NAM, and even that would reach a peak after an hour or so and then decline. Thus it would have to be somewhere between 0% and 20%. I chose a number in the middle to indicate how the reduction of damaged mtDNA varied in a non-linear fashion. It's very slow at first, and then accelerates toward the end.

 

Just to demonstrate my argument with a totally hypothetical example: It could very well be that increasing the concentration of the "trigger" by 4.8 fold (a random number to demonstrate a principle) above baseline may result in 20% reduction in defective mitochondria, while increasing the same substance by 2.4 fold in the same tissue may eliminate almost no defective mitochondria at all. 

 

There is always some natural fission, and that will increase with the level of NAM. There is certainly some NAM level beyond which no further advantage is obtained. That isn't a problem, as the cell can only deal with so much recycling in one day. Lysosomes have limited capacity and can take up to a day to digest mitochondria.

 

I would very much expect -again based on no concrete data whatsoever- that possibly the various defective mitochondria will exhibit varying degrees of resistance to elimination/clearance, making each round less effective at some point and then almost completely ineffective at a later stage at some point. To continue to be equally successful in removing them at each pass appears very likely.

 

Did you mean very unlikely? If that were true, then the fusion and fission curves would never intersect. But they did. I didn't use this test with the first protocol, and I expect that they would not have intersected, as the first protocol depended entirely on PINK1/Parkin removal, which doesn't label mitochondria with methylation damage as it isn't severe enough. ΔΨm doesn't go to zero, which the QC process depends on. So in that case, I would expect your last two sentences to reflect what would happen.

 

I showed experimental results of a cyclic treatment in post 1739...You did not. To attach the term "experimental results" to what you have presented just demonstrates a totally unwarranted degree of confidence in your casual, personal observations.

 

It was a real experiment. I didn't use rats and I didn't use a group of subjects, but it was an actual experiment. Those in the athletic supplement business use these sort of experiments frequently. 

 

The reality is that boosting endurance with any sort of intervention -except of course specific exercise regimens- is extremely hard.

 

So you haven't had success before. That doesn't mean someone else won't. Thus not an argument.

 

The results that you keep posting in this as well as other threads are so outrageous that they are simply not credible in the least and erode almost all credibility. Increasing endurance measurably with just a few cycles of the above???

 

What other results do you refer to? That my epigenetic age dropped by 20 years? Just because for thousands of years we've never been able to age backwards doesn't mean it's impossible. And in fact, it's not really that difficult.

 

People commenting that you actually look younger after 2 weeks of something???

 

Actual epigenetic tests, before and after. 

 

In another thread regarding the use of red light, you posting that with the use a very weak light source, immediately feeling a reduction in hunger and then seeing dramatically accelerated fat loss on top of that? These claims are so outrageous that they are simply impossible to take seriously, thus also casting an unfavorable light on the rest of the discussion. 

 

Other people have seen it too. And nothing magic about it. Stimulating the release of a small amount of triglycerides into the blood can make a substantial difference in one's ability to deal with hunger. By itself it achieves little or nothing for weight loss, but combined with fasting and exercise, it can be quite effective. (I expect you're throwing in that red light thread as the kitchen sink.)

 

 

 

Edited by Turnbuckle, 26 February 2021 - 03:18 PM.