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Manipulating mitochondrial dynamics

nad nad+ c60 mito fission fusion stearic acid mtdna methylene blue

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#211 StanG

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Posted 02 July 2017 - 01:11 PM

I use Stearic in hot green tea but I don't make it too hot or it will form a slick surface on top. At times I put a small ice cube in the tea. I also use Splenda. I swish around my mouth with cold water several times while drinking this to rinse away the granules that seem to hide in my mouth. I prefer to do this on an empty stomach and wait 1 1/2 hours to eat any food.    

 

P.S. My English teacher would give this an "F" for using "I" to start too many sentences.


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#212 RWhigham

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Posted 02 July 2017 - 06:28 PM

 
This article begins by showing a couple of mitochondria which fused over a period  of 20 seconds after being stimulated with 2 photons from a laser.
 
The fused state lasted for about 1-2 minute during which the best and worst respiration elements evidently segregated to opposite ends of the fused pair.
 
After 1-2 minutes the fused pair fissioned into a daughter with high membrane potential and a daughter with low membrane potential.
 
It was shown that some daughters with low membrane potential recover membrane potential after a couple of hours, while others never recover.
 
In another experiment, fusion was stimulated in a large assemblage of mitochondria.
 
Fusion was quickly followed by fission with 65% fissioned just 2 minutes after the fusion, 75% fissioned 5 minutes after fusion, the rest approaching 100% fissioned asymptotically.
 
Fusion was observed to begin again spontaneously after a minute or so in the fissioned state. After 20 minutes 25% of the mitochondria had fused again but the rate of fusion had  dropped to approximately zero leaving 75% of the mitochondria in a fissioned state.
 
It was shown that the fissioned mitochondria that did not regain membrane potential could never fuse again and became targets of  phagosomes.
 
Mitophagy was shown to preferentially eliminate the mitochondria with low membrane potential. It takes 24 hours or longer for this to occur.
 
Inhibiting fission or inhibiting phagosomes prevented mitophagy and reduced respiration by 50% after 5 days.
 
Daily quality control seems to be the way respiration is maintained, else it can decline very rapidly. It requires 
  • Fusion and segregation of strong and weak respiration elements to opposite ends
  • Fission into healthy and defective daughters, and
  • Mitophagy over a 24 hr or longer period to eliminate the defective daughters (which are excluded from the fusible population)
Mitochondria appear to have a harsh internal environment and require this constant on going cleanup.  
 

Edited by RWhigham, 02 July 2017 - 06:37 PM.

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#213 zorba990

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Posted 03 July 2017 - 12:41 AM

At this point I feel comfortable with taking fission enhancers at 5am, workout at about 6 and nothing but some whey and electrolytes until about 10am 3x a week. Then a small meal with antioxidants and some of the fusion enhancers but no stearic acid until around 5pm. But if I can eat it hot then I'll probable have the stearic acid sooner.

I am using super strict form and slow negatives which is helping me use less weight. But I still plan on slowly increasing weights just micro loading for now. I feel that there has to be some kind of progressive overload for improvement to continue kaatsu is interesting. By I'm not sure about the "decrease in vascular function" being a good thing

https://www.ncbi.nlm...les/PMC2903220/

"Conclusion
These data indicate that forearm exercise training combined with restricted venous blood flow results in a significant increase in muscular strength, coupled with a significant decrease in vascular function (reduced vasodilation). The contrasting change in vascular function following exercise training with venous blood flow restriction in the forearm may, in part, be the consequence of significant alterations in blood flow patterns during handgrip exercise."

#214 RWhigham

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Posted 04 July 2017 - 05:12 AM

 

 
This article begins by showing a couple of mitochondria which fused over a period  of 20 seconds after being stimulated with 2 photons from a laser.
 
The fused state lasted for about 1-2 minute during which the best and worst respiration elements evidently segregated to opposite ends of the fused pair.
 
After 1-2 minutes the fused pair fissioned into a daughter with high membrane potential and a daughter with low membrane potential.
 
It was shown that some daughters with low membrane potential recover membrane potential after a couple of hours, while others never recover.
 
In another experiment, fusion was stimulated in a large assemblage of mitochondria.
 
Fusion was quickly followed by fission with 65% fissioned just 2 minutes after the fusion, 75% fissioned 5 minutes after fusion, the rest approaching 100% fissioned asymptotically.
 
Fusion was observed to begin again spontaneously after a minute or so in the fissioned state. After 20 minutes 25% of the mitochondria had fused again but the rate of fusion had  dropped to approximately zero leaving 75% of the mitochondria in a fissioned state.
 
It was shown that the fissioned mitochondria that did not regain membrane potential could never fuse again and became targets of  phagosomes.
 
Mitophagy was shown to preferentially eliminate the mitochondria with low membrane potential. It takes 24 hours or longer for this to occur.
 
Inhibiting fission or inhibiting phagosomes prevented mitophagy and reduced respiration by 50% after 5 days.
 
Daily quality control seems to be the way respiration is maintained, else it can decline very rapidly. It requires 
  • Fusion and segregation of strong and weak respiration elements to opposite ends
  • Fission into healthy and defective daughters, and
  • Mitophagy over a 24 hr or longer period to eliminate the defective daughters (which are excluded from the fusible population)
Mitochondria appear to have a harsh internal environment and require this constant on going cleanup.  

 

According to the above, mitochondria can cycle several times an hour between fission and fusion.
During each cycle damaged elements are purged.
 
I'm having a hard time reconciling the above article with the Turnbuckle Protocol. Any insight would be appreciated.
 
In the above article, after the post fission stimulus, the % of fused mitochondria rose to 25% and then quit changing, At that time the rates of fusion and fission were balanced. 
    let N be the total number of mitochondria
    Then (0.25)(N) is the number fused, and (0.75)(N) is the number fissioned.
 
   fissions/sec = (0.25)(N)/T1 where T1 is how long it takes a fission to occur
   fusions/sec = (0.75)(N)/T2  where T2 is how long it takes a fusion to occur.
 
    fissions/sec = fusions/sec  in steady state
    (0.25)(N)/T1 = (0.75)(N)/T2
           T2/T1 = 3 
So these mitochondria spent 3 times longer fissioned than fused - ball park 20 minutes fissioned and 7 minutes fused, completing a quality control cycle every 27 minutes on average.
 
"The fraction of mitochondria that are fused depends on the relative rates of fission and fusion."  The fusion/fission ratio changes with circumstances (and in different  tissues). Starvation (AMPK CR) increases fusion. Unintuitively low-level toxins increase fusion even though mitochondrial damage increases fission. This  following proteins control fission/fusion
  Fission - Drp1
  Outer membrane fusion -  Opa1 (and cardiolipin)
  Inner membrane fusion - either  Mfn1, MFn2, or both (and cardiolipin)
 

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#215 stephen_b

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Posted 04 July 2017 - 07:53 AM

From :

"Astaxanthin-potentiated mitophagy and fusion would link to decreased energy expenditure in wild type mice.” Having something that increases mitophagy could be useful in this protocol.

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#216 Advocatus Diaboli

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Posted 04 July 2017 - 08:02 AM

Your fission equation uses the number of fused mitos (0.25N) and your fusion equation uses the number of fissioned mitos (0.75N).

I can't find the text of your quote "The fraction of mitochondria that are fused depends on the relative rates of fission and fusion." in either of the main texts of the hyperlinks in your post (#214). I didn't check text in figures, etc. Where is the quote from? I didn't fully read the texts, just did a simple ctrl-f search, so I may have missed it.

There doesn't seem to be enough information to understand how a steady state can be reached with a presumably static number, N, of mitos. If after each fission there is a certain number of the low-membrane-potential daughter products that can't re-fuse then the number of fissioned mitos available for fusion will diminish over time with each fission in the fission-fusion cycle.

Do the authors mention any type of "mass-balancing" to keep the total number of mitos, N, a constant number? Perhaps they found a way to re-establish favorable membrane potential, or whatever the governing factor is, in daughters that otherwise would not re-fuse?



#217 Andey

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Posted 04 July 2017 - 09:01 AM

 

 
I'm having a hard time reconciling the above article with the Turnbuckle Protocol. Any insight would be appreciated.
 
 

 

  

   Apparently the intervention itself is working but rationale is a bit simplistic.

Look at Fafner55`s rationale for 5 days NAD increasing protocol http://www.longecity...e-2#entry791908. Its not speculative and underlying study shows clear net result in mitochondrial dynamics.

  Turnbuckle uses shorter cycles with enhanced metabolic damage (sports science term) from exercise. Its not too far stretched and no brainer if you want to include exercise benefits and muscle hypertrophy. On the other hand its more risky from longevity perspective as too much exercise speedup aging and optimal spot for it is quite low. (around 2.5 hours light jogging a week per Copenhagen heart study). 


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#218 Turnbuckle

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Posted 04 July 2017 - 09:35 AM

 

Fission and selective fusion govern mitochondrial segregation and elimination by autophagy - This article contains a wealth of material.

 
...Mitochondria appear to have a harsh internal environment and require this constant on going cleanup.  

 

 
According to the above, mitochondria can cycle several times an hour between fission and fusion.
During each cycle damaged elements are purged.
 
I'm having a hard time reconciling the above article with the Turnbuckle Protocol. Any insight would be appreciated.

 

 

In a normal healthy state, defective mitochondria are purged continuously and the population remains healthy as long as the machinery works as it's supposed to and as long as pathological mitochondria do not appear that don't produce ATP but resist elimination. See these two posts from last year, regarding zombie mitochondria--

 

http://www.longecity...ndpost&p=772985

http://www.longecity...ndpost&p=772828

 

If the mito machinery always worked perfectly then we would have youthful vitality for a lot longer than we do. So this protocol is intended as a spring cleaning, clearing out virulent and defective cellular machinery so that normal maintenance processes can function once again. A secondary purpose is to increase the effectiveness of exercise as in Exercise Like a Girl.


Edited by Turnbuckle, 04 July 2017 - 10:26 AM.

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#219 RWhigham

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Posted 04 July 2017 - 02:20 PM

Your fission equation uses the number of fused mitos (0.25N) and your fusion equation uses the number of fissioned mitos (0.75N).

This is correct, the number of fused mitos are the ones fissioning, and the number of fissioned mitos are the ones fusing.

 

I can't find the text of your quote "The fraction of mitochondria that are fused depends on the relative rates of fission and fusion." in either of the main texts of the hyperlinks in your post (#214). I didn't check text in figures, etc. Where is the quote from? I didn't fully read the texts, just did a simple ctrl-f search, so I may have missed it.

I should not have used quotes. A bad mistake on my part. A proper quote from the abstract is "The lengths of mitochondria and the degree to which they form closed networks are determined by the balance between fission and fusion rates."  The point I wanted to make is that during any short time period there is a balance between fission and fusion rates, It is a dynamic balance that is easily changed.  I believe it's self evident that the fractions of fused mitos and fissioned mitos is determined by the balance between these two rates. 

 

There doesn't seem to be enough information to understand how a steady state can be reached with a presumably static number, N, of mitos. If after each fission there is a certain number of the low-membrane-potential daughter products that can't re-fuse then the number of fissioned mitos available for fusion will diminish over time with each fission in the fission-fusion cycle.

In the experiment referenced, after fissioning all the mitos, the number of fused mitos grew to 25% over a period of 20 minutes. A curve showing the increase with time was given.  At the end of 20 minutes the curve had gone flat and the fraction of fused mitos was no longer increasing. I assume a balance between fission and fusion was reached at that point in time - a quasi steady state. Steady state does not apply over longer periods of time.

 

Do the authors mention any type of "mass-balancing" to keep the total number of mitos, N, a constant number? Perhaps they found a way to re-establish favorable membrane potential, or whatever the governing factor is, in daughters that otherwise would not re-fuse?

The total number of mitos were not monitored.

They did not investigate the internal workings of daughters that regained membrane polarity.

 


Edited by RWhigham, 04 July 2017 - 02:55 PM.


#220 HighDesertWizard

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Posted 04 July 2017 - 02:33 PM

Apparently, mitochondrial dynamics can be manipulated in at least one context by Vagus Nerve stimulation...

 

Vagal nerve stimulation improves mitochondrial dynamics via an M3receptor/CaMKKβ/AMPK pathway in isoproterenol‐induced myocardial ischaemia


Edited by HighDesertWizard, 04 July 2017 - 02:33 PM.

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#221 RWhigham

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Posted 04 July 2017 - 03:28 PM

If the mito machinery always worked perfectly then we would have youthful vitality for a lot longer than we do. So this protocol is intended as a spring cleaning, clearing out virulent and defective cellular machinery so that normal maintenance processes can function once again. A secondary purpose is to increase the effectiveness of exercise as in Exercise Like a Girl.

Turnbuckle I'm thankful for this thread.

I surely want to reverse the lifelong decline in my cellular respiration.

 

VO2 max can show a person's respiration age. Do you think this would be a valid measure of success?

Google "VO2 max testing <your locale>".  $99 where I live.

 

I can use calories/min and heart rate from my fitbit for a less accurate measurement, possibly for before and after comparisons,

   See post #100 in this thread  - I don't know how to link directly to another post


Edited by RWhigham, 04 July 2017 - 04:05 PM.


#222 BigLabRat

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Posted 04 July 2017 - 05:31 PM

 

 

Mechanisms of Mitochondrial Fission and Fusion "The fraction of mitochondria that are fused depends on the relative rates of fission and fusion."  The fusion/fission ratio changes with circumstances (and in different  tissues). Starvation (AMPK CR) increases fusion. Unintuitively low-level toxins increase fusion even though mitochondrial damage increases fission. This  following proteins control fission/fusion
 
 

 

Interesting, and rather odd.

 

I looked up the paper and found this: "Two opposing trends in fission and fusion rates are used to counter different levels of stress: increased fusion and/or decreased fission helps overcome low levels of stress, whereas decreased fusion and/or increased fission occurs with high levels of stress. Low levels of stress are seen with starvation, during which mitochondrial fission is inhibited to protect cells from excessive autophagosomal degradation of mitochondria (Gomes et al. 2011; Rambold et al. 2011)."

 

​We seem to be getting contradicting reports on fasting.

 

​This might be consistent with Longo's reports of fasting protecting healthy cells during chemotherapy. 

 

​But I'm getting confused by the seeming contradictions regarding calorie intake and fission/fusion.

 

Thoughts, anyone?



#223 zorba990

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Posted 04 July 2017 - 05:56 PM

Fasting plus high intensity exercise is likely to be different from fasting and resting. For me, I am trickling in electrolytes and carbs during mid to end of the workout in order to keep up the stress levels (even though I have cut the volume down already) but really once the niacinamide and ribose kicks in I can feel the added stress.

I'm starting to think that withholding fusion enhancers is missing a critical post weights exercise window for fusion. This is fine for short term detox but longer term I think I'll just go back to post workout shakes with lots of antioxidants and fusion enhancers shortly after loading butyrate. If this has worked I should be able to hit new prs even with slow strict form (although it may take a few months) time will tell.....

#224 Shai Hulud

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Posted 04 July 2017 - 08:43 PM

 

 

 

Mechanisms of Mitochondrial Fission and Fusion "The fraction of mitochondria that are fused depends on the relative rates of fission and fusion."  The fusion/fission ratio changes with circumstances (and in different  tissues). Starvation (AMPK CR) increases fusion. Unintuitively low-level toxins increase fusion even though mitochondrial damage increases fission. This  following proteins control fission/fusion
 
 

 

Interesting, and rather odd.

 

I looked up the paper and found this: "Two opposing trends in fission and fusion rates are used to counter different levels of stress: increased fusion and/or decreased fission helps overcome low levels of stress, whereas decreased fusion and/or increased fission occurs with high levels of stress. Low levels of stress are seen with starvation, during which mitochondrial fission is inhibited to protect cells from excessive autophagosomal degradation of mitochondria (Gomes et al. 2011; Rambold et al. 2011)."

 

​We seem to be getting contradicting reports on fasting.

 

​This might be consistent with Longo's reports of fasting protecting healthy cells during chemotherapy. 

 

​But I'm getting confused by the seeming contradictions regarding calorie intake and fission/fusion.

 

Thoughts, anyone?

 

 

 I think fasting should protect healthy cells in chemotherapy, because it will reduce the ROS produced my mitochondria.

Even all healthy mitochondria with a body in perfect shape and optimal levels of nutrients should reach a point, where

they can't neutralize the super oxide produced in complex I - might be pretty normal under realistic conditions. 

The oxidative stress is essential for the chemotherapy, because you want the cancerous cells to die from it (or more easily),

but of course, it's an side effects affecting all the healthy cells, too.

 

The high NAD+/NADH ratio means energy shortage and will uncouple OXPHOS and (from what I understand) is so effective, because it is normally a signal of very high effort. The exercise amplifies this. 

Is it possible ratios are high are normally very hard to reach? Could be possible, as the amounts of precursors (NAA, ribose) are pretty high, especially on an empty stomach with activation of NAMPT (through SIRT1). If high ratio means low energy, does this especially high ratio also signalize there's generally an excellent provision of food and it's time for fission? Or do they do it to re-couple OXPHOS?

 

As both conditions (coupling/uncoupling) go hand in hand with voltage of the membrane, a newly fissioned mitochondrion which is damaged, regarding it's DNA or membrane condition, won't be able to effectively re-couple OXPHOS and thus the membrane potential will stay low (or vice versa).  

 

This mechanism is also used by the cell for the innate immune response (actually they are pretty much the same) Pathogens entering the cell will uncouple OXPHOS, by quickly changing membrane potential. Influx of nutrients (I think also other things)into mt will be disturbed, changing the important ratios. The quicker the pathogen acts, the more it will disturb the happenings in the cytosol and the faster ratios  in mt will change. As a result, uncoupling will be stronger and ROS generation also more strong. Best case, the ROS kill the pathogen(s), before apoptosis is initiated. In this case the cell will repair itself. I guess the fission is also the cell's/mitochondria's way to modulate oxidative load. If mitochondria could not fission in this situation, their re-coupling would be much harder, while some of the damage could never be undone. 

This is the oldest weapon of the immune system and at it's core it's the same for all stress (physical, chemical, bacterial, viral...).

It fights the stressors, but it can also damage the body and will, if the stress is too strong and/or doesn't end. 

Has the best cost-benefit relation in better adapting tissue like muscle (which as one reason, can divide), but is less good in nervous tissue, which is very dependent on energy and harder to repair.

 

Also the reason I didn't try it yet: As described by others  it seems to does work fine for muscles (and other tissues as it sounds), but what will be happening in already weakened neurons or astroglia?

 

I think this paper gives a good idea of the described: http://www.sciencedi...567724913002390


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#225 BigLabRat

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Posted 05 July 2017 - 06:20 AM

Fascinating. But what puzzles me are the previous references to fission being inhibited by being in the 'fed" state.

 

The situation with nutrition and exercise strike me as being vitally important to our overall strategy here...



#226 hotbit

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Posted 05 July 2017 - 07:21 AM

Fascinating. But what puzzles me are the previous references to fission being inhibited by being in the 'fed" state.

 

The situation with nutrition and exercise strike me as being vitally important to our overall strategy here...

 

 

I've already mentioned here and here that feeded state leads to fission, not fusion. I don't remember anyone to state otherwise. The goal of forcing fission in fasting state is to enhance autophagy (mitophagy), i.e. eliminate defective mitochondria.

 

Worth to read through the thread again, as topic is so difficult and easily confusing, plus it's work in progress - anyway, some questions are already answered.

 

Hope it helps.


Edited by hotbit, 05 July 2017 - 07:30 AM.


#227 Empiricus

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Posted 05 July 2017 - 06:18 PM

I did 2 days of fission, followed by 2 days of fusion.  Now I'm onto another day of fission.  One thing I have noticed is reduced appetite.  For example, I decided I would eat plenty of chocolate to get my stearic acid during fusion, but I practically had to force myself to eat it.  Have others noticed reduced appetite on this protocol?  


Edited by Empiricus, 05 July 2017 - 06:24 PM.


#228 Shai Hulud

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Posted 05 July 2017 - 10:10 PM

Not wanna go too far OT, but has anyone ever tried intermittent intermittent hypoxia-hyperoxia training (IHHT)?

 

They have been researching this In Russia and other Eastern European states for many years and seem to have used it for training of astro-/cosmonauts.

Some doctors are now offering it here in Germany, through the machines are pretty expensive and thus you'll leave a lot of many there if you need many sessions.

 

Unfortunately, most research is only available in Russian, so it's not so easy to get all the information.

Here's one paper Adaptations following an intermittent hypoxia-hyperoxia training in coronary artery disease patients: a controlled study;

 

I imagine Turnbuckle's protocol to be cheaper (if you don't already have a machine) and also more effective,

though I could imagine a combination of IHHT and supplements would be better. Plus, IHHT could be useful in cells

that aren't easy to actively use, contrary to large muscles.


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#229 Andey

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Posted 06 July 2017 - 04:05 AM

Not wanna go too far OT, but has anyone ever tried intermittent intermittent hypoxia-hyperoxia training (IHHT)?

 

They have been researching this In Russia and other Eastern European states for many years and seem to have used it for training of astro-/cosmonauts.

Some doctors are now offering it here in Germany, through the machines are pretty expensive and thus you'll leave a lot of many there if you need many sessions.

 

Unfortunately, most research is only available in Russian, so it's not so easy to get all the information.

Here's one paper Adaptations following an intermittent hypoxia-hyperoxia training in coronary artery disease patients: a controlled study;

 

I imagine Turnbuckle's protocol to be cheaper (if you don't already have a machine) and also more effective,

though I could imagine a combination of IHHT and supplements would be better. Plus, IHHT could be useful in cells

that aren't easy to actively use, contrary to large muscles.

 

 I imagine its quite easy to try with something like Frolov breathing trainer(easy to DIY device) or simple apnea training for hypoxia and holotropic breathing for hyperoxia (kinda an essense of Wim Hof method)


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#230 hsibai

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Posted 06 July 2017 - 06:50 AM

I did 2 days of fission, followed by 2 days of fusion. Now I'm onto another day of fission. One thing I have noticed is reduced appetite. For example, I decided I would eat plenty of chocolate to get my stearic acid during fusion, but I practically had to force myself to eat it. Have others noticed reduced appetite on this protocol?

I also noticed decreased appetite for food. Might be useful in shedding off some of that abdominal fat for me at least.

So if Mito can change from fission to fusion state in minutes why are the fission/fusion protocols not being done on the same day?

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#231 Shai Hulud

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Posted 06 July 2017 - 12:09 PM

 

Not wanna go too far OT, but has anyone ever tried intermittent intermittent hypoxia-hyperoxia training (IHHT)?

 

 

 

 I imagine its quite easy to try with something like Frolov breathing trainer(easy to DIY device) or simple apnea training for hypoxia and holotropic breathing for hyperoxia (kinda an essense of Wim Hof method)

 

 

 

As I see you are from Ukraine, do you have any experiences with this or know how exactly this works?

I've read some threads on German forums from people with similar plans, but the consensus seemed to be it's

not the same. Someone bought a machine from an Australian company (as far as I remember).

The fast changes seem to be important.

 

Here's an link to a German company selling the machines to doctor's here. The doctor behind has a pretty impressive professional vita,

but not sure if he somehow switched to the dark side in recent years (now also has a beauty clinic).


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#232 zorba990

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Posted 06 July 2017 - 11:36 PM

I did 2 days of fission, followed by 2 days of fusion. Now I'm onto another day of fission. One thing I have noticed is reduced appetite. For example, I decided I would eat plenty of chocolate to get my stearic acid during fusion, but I practically had to force myself to eat it. Have others noticed reduced appetite on this protocol?



Yes, reduced appetite, close to saying reduced need for sleep but still tracking on that one...

#233 hsibai

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Posted 10 July 2017 - 08:04 PM

This silence is very unusual for this thread. Are we due for taking stock of what we have? Perhaps a summary post of findings / conclusions?

I personally think we are nowhere near the end of this thread. Please share your experience so we can all benefit.

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#234 RWhigham

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Posted 10 July 2017 - 11:46 PM

The protocols in this thread are based on the premise that increasing NAD+ "increases fusion". I've been thinking about what it means to "increase fusion" and arrived at the following possibility:
 
A mitochondria typically spends 7 sec fused and 21 sec fissioned, and completes a housekeeping cycle every 28 sec. Once things have equilibrated, a snapshot at any given point in time will show 75% of the mitochondria fissioned and 25% fused.
 
Now if a mitochondria spends less time fissioned, say 7 sec, a complete cycle will take just 14 sec. Once things have equilibrated, a snapshot at any given point in time will show 50% of the mitochondria fissioned and 50% fused. An observer would say "fusion has increased".
 
We know that low-level toxins "increase fusion". If the mitochondria are trying to detox, then it seems plausible that they would increase the rate of housekeeping cycles per second, which as we have seen,  "increases fusion".
 
If you badly damage a lot of mitochondria, the number of defective daughters would rise so high it would appear as "increased fission". But if we could only look at the mitos still participating in housekeeping cycles, we would likely see "increased fusion", as the cycle rate maxed out trying to fix things.
 
Thus it's possible that our protocol of increasing NAD+ to "increase fusion" has the primary effect of increasing the rate of fusion/fission cycles per minute, possibly doubling them.
 
Andey's post  #217 references a protocol of raising NAD+ with Niagen. It reduced total mitochondrial mass by 50% after 5 days. This also seems to indicate the housekeeping cycles were running faster and biogenesis could not keep up.
 
This thread is actually based on NAD+ increasing fission. RWhigham misspoke.  - Max Watt

Edited by maxwatt, 23 July 2017 - 12:49 AM.

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#235 Advocatus Diaboli

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Posted 11 July 2017 - 04:26 PM

RWhigham, thanks for mentioning VO2 Max https://en.wikipedia.org/wiki/VO2_max in post #221. I checked for the availability of testing sites in the area I live in and found a place for $100--which was significantly cheaper than at other facilities in my area.

 

In addition to the VO2 Max they offer RMR https://en.wikipedia..._metabolic_rate and DEXA  https://en.wikipedia..._absorptiometry scanning for body fat, muscle, and bone. They had a package deal for $235 so I ordered the package online and went in for the tests last Saturday.

 

I think the differences (if any) between my "baseline" measurements and the measurements I will have taken 5 or 6 months from now will be interesting to look at because, for one, I'll be using one of Turnbuckle's fission-fusion protocols in the intervening time.


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#236 Advocatus Diaboli

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Posted 11 July 2017 - 08:34 PM

RWhigham, I just read your post #100 in this thread and the numbers you present are truly impressive for heart rate, heart-rate recovery, and for estimated VO2 Max.

By using a simple 220-age formula for determining estimated max heart rate, your calculated  max heart rate would be about 142 and that would be a for a full-bore exertional effort.

You mention a "very fast" walk, but if you had any extra "steam" to pile on, by running at times during the walk for example, perhaps you could have gotten your heart rate even higher. If your Fitbit is accurate and you did, at times, peak at 180bpm, then your max heart rate at that time was about 127% of the max rate expected for your age--absolutely awesome.

Your impressive estimated VO2 Max would seem to be consistent with your max heart-rate measurements as well as the phenomenal heart-rate recovery you mention--"immediately" dropping to 75 at the conclusion of your walk.

 

Which begs the question of your resting heart rates before and after you had been on your fission fusion protocol for some time--how long were you on a fission-fusion protocol before the walk mentioned in post #100?

 

And, do you currently have any results of recent 5-mile walks, etc., which may indicate that the type of result you reported on your post #100 isn't anomalous?

Also, the following may interest you:

Oxidative DNA damage induced by a melatonin metabolite, 6-hydroxymelatonin, via a unique non-o-quinone type of redox cycle

https://www.ncbi.nlm...pubmed/15450952

I only have access to the abstract.


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#237 RWhigham

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Posted 12 July 2017 - 12:25 AM

By using a simple 220-age formula for determining estimated max heart rate, your calculated  max heart rate would be about 142 and that would be a for a full-bore exertional effort. You mention a "very fast" walk, but if you had any extra "steam" to pile on, by running at times during the walk for example, perhaps you could have gotten your heart rate even higher. If your Fitbit is accurate and you did, at times, peak at 180bpm, then your max heart rate at that time was about 127% of the max rate expected for your age--absolutely awesome.

 

The "max heart rate" formula was originated as the limit for cardiac patients that might die if pushed too hard during treadmill tests. It was basically a safety net. It caught on without any justification as a "max rate vs age for everyone".

 

Fitbit's HR measurements are sometimes erratic during exercise, but just swinging my arms quickly while walking may have been ok. I believe the calculated kcal/sec was fairly accurate.

 

I don't know if I reached VO2max, but assume I was close at 180 bpm. I was sprinting a block, then walking until I caught my breath. It took several blocks of walking to catch my breath, so most of the time I was just walking (very fast).

 

Which begs the question of your resting heart rates before and after you had been on your fission fusion protocol for some time--how long were you on a fission-fusion protocol before the walk mentioned in post #100?

 

 See post #104 and #114 for details of the 3 times I've done the protocol

 

And, do you currently have any results of recent 5-mile walks, etc., which may indicate that the type of result you reported on your post #100 isn't anomalous?

 

I have not repeated any more fission experiments after post #114. I have been studying to understand the protocol better first. Perhaps keeping NAD+ elevated for a few weeks might be the way to go. See Fafner55 posts at Protocol to Upgrade Mitochondria (Turnbuckle's previous thread)  I would adjust the amount of NAD+ elevation to avoid feeling too sick.


Edited by RWhigham, 12 July 2017 - 12:55 AM.


#238 Advocatus Diaboli

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Posted 12 July 2017 - 02:28 AM

RWhigham, you wrote in post #237: "The "max heart rate" formula was originated as the limit for cardiac patients that might die if pushed too hard during treadmill tests. It was basically a safety net. It caught on without any justification as a "max rate vs age for everyone". If you are healthy it does not apply."

 

Yeah I knew that, that's why I used the word "simple" to describe it. Easier to remember and mentally compute than HRmax = 203.7 / ( 1 + exp( 0.033 × (age − 104.3) ) ), for example.  ;)  Some of the other formulas found here range from about 150 to about 160 bpm for your age. So, for a quick and dirty estimate, 142 (and 142 might be considered auspicious in a certain manner considering the last two digits, heh heh  Douglas Adams ) isn't all that bad depending upon the range of precision one wants to embrace--with the range possibly running the gamut from Fermi to pilpul.

 

In any case, whether the max heart rate for your age is 142, 150 or even 160, hitting 180 (perhaps higher) is somewhat astonishing, as Ayn Rand might have commented upon hearing the heart rate that you obtained (those who have read "Atlas Shrugged" will understand the allusion). :-D

 

Thanks for addressing my questions. As hsibai notes in post #233 we all benefit from reading about the experiences of those who try the Turnbuckle protocols. For my own part, some equipment I'll use include a pulse oximeter to monitor So2 and heart rate, blood pressure device, and a Precor EFX 546 elliptical training machine which displays such things as METS  calories per minute, and strides per minute.

 

I have a balance board and have no problem balancing on it, but it'll be interesting to see if I can work my way up to a few seconds worth of eyes-closed-in-a-darkened-room-with-face-directed-toward-the-ceiling type of balancing in 6 months time (of course I won't know what role the protocol might have played if I see an increase in my ability to balance, but what the heck). NB--I won't be trying the balancing in an Ames Room :|o

 

I have a PC program (not currently available) that has a feature to measure simple visual reaction time. I also have downloaded an n-back variant called dual n-back to assess short-term memory (which is said to increase by virtue of playing n-back in its own right). That's some of my tools and I'd like to hear from others so I can steal your ideas! ;)

 

 


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#239 Empiricus

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Posted 12 July 2017 - 02:15 PM

I did 2 days of fission, followed by 2 days of fusion.  Now I'm onto another day of fission.  One thing I have noticed is reduced appetite.  For example, I decided I would eat plenty of chocolate to get my stearic acid during fusion, but I practically had to force myself to eat it.  Have others noticed reduced appetite on this protocol?  

 

An update on the above post.  That night, I couldn't sleep well and I imagined I was coming down with some kind of disease.   By the second day of my second round of fission, in addition to having no appetite, I felt awful.  Mentally, I felt quite depressed.  As Trump would say, I was "a low energy" person.  I wasn't sure my worsening condition had anything to do with the fission process.  I thought I was just falling apart.  

 

My fission days had entailed a combination of high dose NR + high dose niacinamide spread throughout the day.  Both afternoons, not having access to weights, I ran up and down many flights of stairs. This workout wasn't easy, but I'm not in bad shape.  Certainly by this, my second day of fission, I was feeling more "burn."   

 

By the time the hour of fusion approached, I had given up hope.  My previous 2 days of fusion had been a total disappointment. I had gotten no boost from it whatsoever.  Previously, I had chosen an organic fair-trade 70% cocoa chocolate as my source of stearic acid.  Though I had consumed several hundred grams of this chocolate, it appeared to have done nothing for me, and I had no appetite.  By this, the evening of my second day of fission, I had basically concluded the protocol didn't do anything and that I must have come down with some kind of terrible illness.  

 

When fusion hour arrived, I went to a store and bought a different brand of chocolate. It was a cheaper brand, but 80% cocoa.  I dissolved 35 grams of the chocolate into a mug.  Boom!  I began to feel strong again.  My depression lifted, my appetite returned, and I felt very energetic -- all within 30 minutes of consuming the 80% cocoa.  

 

I continued taking the same brand of 80% cocoa through several days of fusion, and I felt better and better.  It seems chocolate can do the job of kick-starting fusion, but not all brands of dark chocolate contain sufficient stearic acid.  

 

Instead of just 2 days of fusion, I tool a whole week to do fusion this time.  I entirely avoided NR and niacinamide.  In addition to the 80% cocoa, I took curcumin. The week of fusion left me feeling and looking a lot better than I have in months.


Edited by Empiricus, 12 July 2017 - 02:39 PM.

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#240 RWhigham

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Posted 12 July 2017 - 04:19 PM

hypnos said:

. That's some of my tools and I'd like to hear from others so I can steal your ideas!  ;)

 

I use a polar HR chest strap and free Elite HRV heart rate variability app from the Google play-store. I check my HRV most mornings..

 

HRV declines with age and has been suggested as a biomarker for biological age. A low HRV also indicates a sick heart. HRV is affected by how you breathe so one should use a breathing guide and breathe the same during each measurement (5 breaths/minute is standard).

 

HRV varies from day to day. Once a baseline is established, HRV programs use the daily variation to suggest when to exercise hard and when to take it easy.

 

How it works:

An HRV program measures the beat to beat interval NN over some period of time (5 minutes is standard)

  •   The average NN interval is calculated.
  •   The standard deviation of NN is calculated SDNN.
  •   Successive differences from the average are calculated (SDs).
  •   The root mean square of successive differences is calculated rMSSD.
  •   The natural log ln(rMSSD) is calculated
  •   The natural log is multiplied by a constant to get an HRV number between 0 and 100.  HRV = K x ln(rMSSD).

 

K is not standardized so HRV's are not directly comparable between programs. They don't tell you what K they use, but if they give you ln(rMSSD) you can calculate K = HRV / ln(rMSSD).

 

The Elite app saves plots of NN vs.time that you can view. It also saves all your data online. You can download your entire history of NN intervals in a comma separated file and do an HRV frequency analysis with another free program from the web. 

 

My HRV biomarker age is around 20, That makes me feel good, but it's probably an anomaly caused by an unusual beat pattern. When I downloaded 6 months worth of data and did a frequency analysis, there's a double hump in the frequency distribution that is not normal.  Also, I've been cheating by breathing slower and deeper than your are supposed to,

 

To get a valid biomarker of age, you have to get an all-day walking-around HRV instead of a 5 minute one in the morning where your watching it real time and pushing it up with biofeedback.


Edited by RWhigham, 12 July 2017 - 05:17 PM.

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