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Manipulating mitochondrial dynamics

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

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#421 Turnbuckle

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Posted 26 September 2017 - 01:08 PM

I accidentally left off another biogenesis herb--Acacia Catechu extract (which contains epicatechin) -- .5-1 g


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#422 Believer

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Posted 26 September 2017 - 03:22 PM

There's something to the nicotinic acid and carnitine combo that I can't put my finger on but it's done wonders. You probably remember what I am referring to.



#423 Nate-2004

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Posted 26 September 2017 - 03:37 PM

Turnbuckle that AMPK activator is primarily Rose Hips right? Wouldn't metformin or berberine be better? 

 

https://examine.com/...ments/rose-hip/

 

Also, a good cheddar cheese has 200mg/kg of spermidine.


Edited by Nate-2004, 26 September 2017 - 04:25 PM.


#424 Turnbuckle

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Posted 26 September 2017 - 04:51 PM

The LE AMPK product is a couple of extracts--

Serving Size 1 vegetarian capsule
Amount Per Serving
Rose hip extract [from dog rose (aerial part) std. to 5% trans-tiliroside] 373 mg
ActivAMP® gynostemma extract (leaf) 150 mg
Other ingredients: vegetable cellulose (capsule), microcrystalline cellulose, tapioca starch, dextrin, ascorbyl palmitate, silica.
Non-GMO
ActivAMP® is a registered trademark of Gencor.
 

 

 

I'm not promoting this as the only possibility. I'm only listing the supplements in my protocol.


Edited by Turnbuckle, 26 September 2017 - 04:53 PM.

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#425 hotbit

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Posted 26 September 2017 - 05:46 PM

 

 

 

I'll be (re)reading and trying to understand the original link to the mechanisms of fission and fusion but there's also the biogenesis part that I don't understand at all.

 

  • Do we have a running list of fusion/fission promoters somewhere in this thread? We should move those to a separate place or web page or wiki.
  • Is NAM+R or NR the only thing that promotes fission?
[...]

 

Good idea to re-read this thread. Some of your questions are answered in previous posts. For example cold shower also promotes fission. I don't get why to ask others on the 5th or 10th page of the thread to repeat information just because someone is too lazy to read through or is quoting 50 lines long post to comment just with one. Sorry if it sounds unfriendly, but it just makes the thread difficult and irritating to re-read when needed.

 

To gather findings in a new post or wiki page is a good idea.
 


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#426 BieraK

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Posted 26 September 2017 - 09:28 PM

This seems interesting and a bit confusing to me. Could it be a good option to activate fission and mitocohondrial biogenesis (with PQQ for example) at the same time?

With regard to reasons for the decrease in the mitochondrial content, the possibility of down-regulation of mitochondrial biogenesis was ruled out in the previous study on the basis of the finding that the mRNA levels of PGC-1α, NRF-1 TFAM, as well as the ETC proteins were by and large unaffected by NAM treatment, at least soon after the treatment (23). On the contrary, SIRT1 activation has been reported to induce mitochondrial biogenesis, which would result in an increase in the mitochondrial content. In these studies, treatment with either resveratrol (44) or SRT1720 (45) activated PGC-1α and thereby induced mitochondrial biogenesis, which in turn results in an increased aerobic capacity of primary cultured cells or mice. If both mitochondrial autophagy and biogenesis occur simultaneously in a cell, these seemingly contradictory effects of SIRT1 would play an important role in mitochondrial quality maintenance, because mitochondrial biogenesis coupled with active mitophagy would repopulate functional mitochondria, resulting in the restoration of a healthy population of mitochondria (46). However, in our study, no activator, at any concentration, increased the MMP (Fig. 7). This suggests that SIRT1 activation most probably does not induce mitochondrial biogenesis nor activate mitophagy selective for depolarized ones in vitro. It is noteworthy that in a study (47) SIRT1-activated PGC-1α up-regulated gluconeogenic genes but not mitochondrial genes during fasting.



#427 Turnbuckle

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Posted 26 September 2017 - 10:51 PM

This seems interesting and a bit confusing to me. Could it be a good option to activate fission and mitocohondrial biogenesis (with PQQ for example) at the same time?
 

 

I expect not, and here's why: In the most extreme level of fission, a mitochondrion will contain just one loop of mtDNA. Replication is known to take around one hour, and so in that time the mitochondrion will presumably not be producing the normal level of proteins for energy production. Thus it may well be marked as defective and recycled. Whereas if biogenesis occurs in a state of fusion, the mitochondrion will contain many mtDNA loops and so there is always one producing necessary proteins for ATP production. Thus you'll want to combine biogenesis with fusion, not with fission. Cells lacking the proteins that enable fusion have several problems, and are known to be deficient in mtDNA.

 

Moreover, whereas wildtype muscle shows a rapid post-natal increase in mtDNA from weeks 1 to 7, mitofusin-deficient muscle fail to increase mtDNA levels, suggesting a possible defect in mtDNA replication.

 

https://www.ncbi.nlm...les/PMC2876819/

 


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#428 Turnbuckle

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Posted 30 September 2017 - 03:19 PM

Lactate for biogenesis?

 

A high NAD+/NADH ratio promotes mitophagy and thus lowers the cellular mass of mitochondria. It also lowers lactate in vitro when added to cells treated with NAM, while adding lactate in vitro can do the reverse—

 

The [NAD+]/[NADH] ratio is reciprocally regulated by the [pyruvate]/[lactate] ratio through lactate fermentation, and when elevated, it down-regulates the conversion of pyruvate to lactate. Indeed, in the NAM-treated cells, the cellular lactate production, as determined by its concentration in the culture medium, decreased with an inverse correlation to the change in the [NAD+]/[NADH] ratio (Fig. 2A). Meanwhile, the addition of 10 mm lactate to the medium resulted in a decrease in the ratio in the control as well as the NAM-treated cells to the levels well below those of the mock-treated cells (Fig. 2B). Surprisingly, lactate treatment resulted in an increase in the mitochondrial contents of both the control and NAM-treated cells in a dose-dependent manner (Fig. 2C). This indicates that lactate itself or the lactate-induced decrease in the [NAD+]/[NADH] ratio increases the mitochondrial content.

 

https://www.ncbi.nlm...les/PMC3365962/

 

See Figs. A-C.

 

 

 

 

Lactate is a reducing agent, as is ascorbic acid. However, while ascorbic acid lowers [NAD+]/[NADH], it doesn’t increase biogenesis. So like stearic acid is for promoting fusion, lactate may have a special purpose for promoting biogenesis.

 

The results of the present study show that supplementation with vitamin C does not improve but partially decreases the improvement in V̇O2max associated with exercise training in rats and in humans. Moreover, it very significantly hampers endurance capacity in animals, as a result of the decrease in mitochondriogenesis that is normally associated with exercise training.

 

http://ajcn.nutritio...t/87/1/142.long

 

 


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#429 Nate-2004

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Posted 30 September 2017 - 03:36 PM

I always avoid vitamin C and E and other antioxidants on exercise days anyway. Is there another way to get lactate to increase besides exercise? My exercise days only sometimes fall on fusion days, though I'm still sorting out how long to fission and how long to fusion. 



#430 Turnbuckle

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Posted 30 September 2017 - 04:24 PM

I always avoid vitamin C and E and other antioxidants on exercise days anyway. Is there another way to get lactate to increase besides exercise? My exercise days only sometimes fall on fusion days, though I'm still sorting out how long to fission and how long to fusion. 

 

 

I've ordered magnesium lactate to try it out. Note that in Fig. 2C, the resultant mitochondrial content at 10mM lactate for 3 days is truly massive--350% of control. It would be hard to take that much, however. I figure around 6g of magnesium lactate to get just a 1mM level in an 80kg human, and the half life of lactate is rather short, around 20 minutes. However, it might be useful in knocking down the NAD+/NADH ratio.


Edited by Turnbuckle, 30 September 2017 - 04:40 PM.

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#431 Nate-2004

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Posted 30 September 2017 - 05:57 PM

There is evidence that ketones may stimulate mitochondrial biogenesis.

 

I'm only 7 days into the keto diet, my ketone blood test yesterday said I was at 3.0 which is pretty high for being only 7 days in. 

 

I still continue to test lower than 10 milli-g's as far as my tremor goes, but this is only at certain points of the day. At other points it is still up to 150 at times. That said, as I mentioned before I never went below 10 or even 30 on the previous couple months of testing. The overall peak average, however, has dropped over the past several days though. It's hard to know whether this is the protocol or keto without stopping one or the other. It could be both, but given the significant change, it's definitely one or both.

 

I plan to stop keto in about 3 weeks. We'll see then.

 

By the way I added PQQ to my fusion protocol. I've never taken the stuff before. Between fission and fusion, I'm not sure what point into fusion is the best time to take it.



#432 able

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Posted 30 September 2017 - 06:50 PM

Great to hear Nate.

 

I've been doing a version of turnbuckles protocol also, although sometimes using NR instead of N+R.  

 

I've been making a lot of progress lately as far as inflammation, joint pain, more energy ( a lot), better times in sprinting, more weight at gym etc.

 

I've been keto over a year, but tightened it up lately.  And changed the HIIT routine a bit - less often, sprinting instead of other stuff.

 

I believe most of my progress has been lowering blood sugar (keto) to lower inflammation.  But also think their is good synergy with the protocol.

 

I keep thinking I should take something out to better judge if its one thing, or all, but like you, don't want to stop the progress.

 

Is great to hear your results,  since you have a less subjective metric.

 

I will go out on a limb and predict more success for you over the next 3 weeks.  I'd also bet after you stop keto, it will take a week or 2 for the benefit to fade.

 

btw, what is your fasting blood glucose?


Edited by able, 30 September 2017 - 06:52 PM.

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#433 Nate-2004

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Posted 30 September 2017 - 08:18 PM

btw, what is your fasting blood glucose?

 

How do I test this? I have a glucose meter but not sure how long to fast before testing.

 

Something else to note: Grass fed beef and cheeses contain better FA profiles including more stearic acid and 66% less Omega 6, and 4 times more omega 3. I would look at getting some grass fed beef in on the fusion days.

 

Eat more cheddar cheese and soy beans on fission days.

 

Eat more kale, spinach and broccoli of course on fusion days.

 

So far I'm thinking:

 

2 days fission: NR, Fisetin and Berberine

 

4 days fusion: Stearic Acid, PQQ, ascorbic acid and Broccomax

 

Then perhaps either 1 day ramp up to fission... or wind down to fusion... I dunno

 

Also remember that Tryptophan leads to NAD+ but also both melatonin and serotonin when there is no inflammation, but kynurinine if you've got any inflammation (5:45 min mark) which is not good and unfortunately for me, more serotonin means worse tremor.


Edited by Nate-2004, 30 September 2017 - 08:19 PM.

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#434 Nate-2004

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Posted 01 October 2017 - 08:50 PM

 

 

My only concern is that on a high fat low carb diet I'm probably going to end up getting stearic acid from all the food on fission days. What to eat on fission days is definitely something I need to figure out. That smoothie has a lot of antioxidants which may not be good during fission. I could just try to fast mostly but that's tough to do more than once a week.

I would not bother with it as it could be the exact opposite. Overall connection between dietary fat intake and blood levels are quite complex as liver quickly suck all dietary nutrients trough portal vein and actual blood levels depend more on internal production.

 

"– Eating less carbohydrate will make less saturated fat appear in your blood between meals, even if you do eat more saturated fat, and this is most true for the lauric acid and myristic acid in your diet."

https://profgrant.co...-low-carb-diet/

 

 

If this is true, this means that quite possibly, stearic acid has a much shorter half life than 17 hours when on a low carb diet. This may mean I don't worry about going from fusion to fission in one day.



#435 APBT

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Posted 01 October 2017 - 11:51 PM

 

btw, what is your fasting blood glucose?

 

How do I test this? I have a glucose meter but not sure how long to fast before testing.

 

Typically, this is an overnight fast; 8 - 12 hours.  Test when you get up in the morning. 


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#436 Nate-2004

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Posted 02 October 2017 - 01:52 PM

 

 

btw, what is your fasting blood glucose?

 

How do I test this? I have a glucose meter but not sure how long to fast before testing.

 

Typically, this is an overnight fast; 8 - 12 hours.  Test when you get up in the morning. 

 

 

I've taken my glucose twice when fasted, one time it was 90 the other time it was 109 (this morning). I read that 109 isn't good but then read this explanation. Apparently keto can lead to a higher fasted bg rating which is why A1C is a better measure. Wish I had a meter for that. Guess I'd need my own lab for that.

 

My shaking is down even more today, it's a fission day but the end of 3 good fusion days. Typically the most improvement I see is at the end of the first day of fission. It could be because ATP is depleted after a tough workout, who knows? 



#437 able

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Posted 02 October 2017 - 02:26 PM

Yeah, I had some similar variation in bg levels when I first started keto, but it dropped and got more constant on normal day.

 

Congrats on more success with your protocol/diet - hope it continues.


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#438 Turnbuckle

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Posted 03 October 2017 - 12:04 PM

For some time I believed that fission and fusion should be well separated. then more recently I began experimenting with daily fission/mitophagy with fusion/biogenesis inserted almost as an afterthought. Now I’m going back to my first idea—that these things ought to be well separated. This comes from my realization that it’s possible to increase mitochondrial mass far beyond what I expected, and mitochondrial mass (if healthy) is key to cellular health and potential rejuvenation of both the cells and the body.

 

Previously I referenced an in vitro experiment where cells exposed to elevated levels of lactate (10 mM) for three days showed an increase of mitochondria mass of 350% of control. (See Fig. 2C) This is interesting, if not astounding. Also interesting is that the NAD+/NADH ratio is inversely proportional to the lactate/pyruvate ratio (Fig. 2A). High lactate (and low NAD+) appears to be a strong signal for mitochondrial biogenesis. Thus exercise promotes health through all tissues by increasing blood levels of lactate/lactic acid. One minute of extreme exercise can pump up lactate to levels higher than the 10 mM of the in vitro cellular experiment for fifteen minutes (Fig. 6).  Similar levels can be achieved for hours by supplementation, but very high doses of lactate are needed. (See Chart 1, an experiment in rabbits where mg/cc of the y-axis can be converted to mM by multiplying by 11.)

 

 

So the bottom line:

 

1.    For the protocol, 3 or 4 days of fission, then 3 or 4 days of fusion, then at least one day off (esp. if stearic acid is used for fusion).

2.    For fusion/biogenesis, NAD+/NADH should be lowered and the lactate/pyruvate ratio raised (these are inversely linked), and thus the best lactate-raising exercise is high intensity for short periods.

3.    Adding several grams of lactate to the fusion/biogenesis stack is likely helpful.
 

 

Another takeaway from the first paper referenced above, is that the amino acid asparagine is as good as nicotinamide at reducing mito content in vitro.

 

 

 

The cytosolic conversion of NADH to NAD+ can be promoted by an increase in the concentration of aspartate, which can be achieved by the addition to the culture medium of asparagine that is readily converted to aspartate by cytosolic asparaginase (29). We treated cells with 20 mm asparagine or NAD+ (treatment included as a positive control), and the effects on the mitochondrial content and MMP were monitored. Treatment of Asn caused a decrease in the mitochondrial content, with the kinetics being similar to that induced by NAD+ or NAM. For 3 days, nearly 40% reduction in the mitochondrial content was observed in both cases of Asn and NAD+ (Fig. 2D).

 

https://www.ncbi.nlm...les/PMC3365962/

 

 


Edited by Turnbuckle, 03 October 2017 - 12:36 PM.

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#439 Fafner55

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Posted 03 October 2017 - 03:23 PM

 

...mitochondrial mass (if healthy) is key to cellular health and potential rejuvenation of both the cells and the body.

 

No doubt healthy mitochondrial mass is essential to cellular health, but what is the relationship between that and rejuvenation (cellular and organisimal)?



#440 Turnbuckle

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Posted 03 October 2017 - 04:55 PM

 

 

...mitochondrial mass (if healthy) is key to cellular health and potential rejuvenation of both the cells and the body.

 

No doubt healthy mitochondrial mass is essential to cellular health, but what is the relationship between that and rejuvenation (cellular and organisimal)?

 

 

 

A strange question. Do think it would be possible to rejuvenate the cells of the body and not rejuvenate the body as a whole?


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#441 Fafner55

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Posted 03 October 2017 - 05:07 PM

 

A strange question. Do think it would be possible to rejuvenate the cells of the body and not rejuvenate the body as a whole?

 

 

I should have been more clear. I was looking for your definition of rejuvenate. For instance, were you referring to stepped up metabolism, or perhaps an epigenetic change to a more youthful state, or specific tissue regeneration, telomere length homeostasis, etc? What exactly is rejuvenated?


Edited by Fafner55, 03 October 2017 - 05:08 PM.

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#442 Turnbuckle

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Posted 03 October 2017 - 06:01 PM

 

 

A strange question. Do think it would be possible to rejuvenate the cells of the body and not rejuvenate the body as a whole?

 

 

I should have been more clear. I was looking for your definition of rejuvenate. For instance, were you referring to stepped up metabolism, or perhaps an epigenetic change to a more youthful state, or specific tissue regeneration, telomere length homeostasis, etc? What exactly is rejuvenated?

 

 

 

It's nothing magical. We are looking at the same sort of rejuvenation you get from exercise, or that Live Extension claims for PQQ. It has the same source--the increase of ATP by way of increased mito mass. The advantage here is that defective mitochondria are removed,with the goal of producing more healthy mitochondria than can be obtained with either exercise or single agents like PQQ. Clearance of mitochondria doesn't happen with exercise or with PQQ--not any more than it does normally by way of the cell's mito QC processes. The normal QC process (which depends on fission and fusion) work for years, but then begin to decline and the reduction of ATP accelerates the process in a death spiral. Defective mitochondria build up. Zombie mitochondria appear that can be compared to an infection or even cancer within individual cells. By separating fission from fusion and driving them to the limit, the goal is to restore youthful functioning to a degree that cannot be otherwise obtained.

 

When normal mitophagic organelle elimination is suppressed by Parkin insufficiency, abnormal undead or zombie mitochondria accumulate and (as zombies will do) contaminate the normal mitochondrial population by fusing with normal organelles. Mitochondrial fusion that is ordinarily protective, therefore, becomes the mechanism for a general contagion of mitochondrial dysfunction. Interrupting mitochondrial fusion prevents contamination of functionally normal mitochondria by virulent zombie mitochondria, sequestering abnormal mitochondria that can then be removed by alternate, albeit almost certainly less efficient, elimination pathways.
 
 
 

 

 

As for the other things you mentioned, such as telomere length, mitochondrial dysfunction certainly increases the rate of erosion, and thus improving mito heath should slow that down. Studies comparing twins who exercise with those that don't show that effect. Is it possible to lengthen telomeres by restoring mito health to a degree that exercise cannot? That's an open question. There are a lot of open questions.


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#443 Heisok

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Posted 03 October 2017 - 07:23 PM

Turnbuckle, I hope the portion I pasted here is enough.

 

" So the bottom line:

1.    For the protocol, 3 or 4 days of fission, then 3 or 4 days of fusion, then at least one day off (esp. if stearic acid is used for fusion).

2.    For fusion/biogenesis, NAD+/NADH should be lowered and the lactate/pyruvate ratio raised (these are inversely linked), and thus the best lactate-raising exercise is high intensity for short periods.

3.    Adding several grams of lactate to the fusion/biogenesis stack is likely helpful. "

 

Does this mean 3 or 4 days practicing fission supporting methods every day, followed by 3 or 4 days practicing fusion supporting methods? I do not expect you to write the whole supplement/exercise breakdown, as you have mentioned all the possibilities so far, and it is not static. I can not follow any of your complete protocols, but am simply trying to stack the odds in favor of fission on some and fusion on other days. The high intensity proposal by you seems to support what some emphasize about high intensity interval training only being needed 1 or 2 days maybe 3 a week maximum. On your exercise less intensely days, do you think the lifting even at much lower than normal weight produces much Lactic acid? (I use less intensely instead of "like a girl" , because  most girls work harder than me to start with :-D :-D)

 

  I believe my 6 interval cycles of 45 seconds of  high intensity followed by 20 seconds of lower intensity "rest" might be close enough to 1 minute.



#444 Turnbuckle

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Posted 03 October 2017 - 07:51 PM

Turnbuckle, I hope the portion I pasted here is enough.

 

" So the bottom line:

1.    For the protocol, 3 or 4 days of fission, then 3 or 4 days of fusion, then at least one day off (esp. if stearic acid is used for fusion).

2.    For fusion/biogenesis, NAD+/NADH should be lowered and the lactate/pyruvate ratio raised (these are inversely linked), and thus the best lactate-raising exercise is high intensity for short periods.

3.    Adding several grams of lactate to the fusion/biogenesis stack is likely helpful. "

 

Does this mean 3 or 4 days practicing fission supporting methods every day, followed by 3 or 4 days practicing fusion supporting methods? I do not expect you to write the whole supplement/exercise breakdown, as you have mentioned all the possibilities so far, and it is not static. I can not follow any of your complete protocols, but am simply trying to stack the odds in favor of fission on some and fusion on other days. The high intensity proposal by you seems to support what some emphasize about high intensity interval training only being needed 1 or 2 days maybe 3 a week maximum. On your exercise less intensely days, do you think the lifting even at much lower than normal weight produces much Lactic acid? (I use less intensely instead of "like a girl" , because  most girls work harder than me to start with :-D :-D)

 

  I believe my 6 interval cycles of 45 seconds of  high intensity followed by 20 seconds of lower intensity "rest" might be close enough to 1 minute.

 

 

What might be best for an individual depends on where they are with mito damage. If they are just starting out and think their mitochondria might not be in good shape (the reason they'd want to try this to begin with), they might not want do three days in a row of anything. Damaged mitochondria do have to be digested and there's limited cellular capacity for that. And it can take more than a day. As for exercise, I find fission goes well with weights and fusion with high intensity. I can get a more substantial burn during fission with less weight than I can during fusion. In fact, with fusion I feel that I am just wasting my time in the gym.


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#445 Heisok

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Posted 03 October 2017 - 08:41 PM

Thanks Turnbuckle. (Since I wanted to post a Thank you anyway, I will throw a comment from another thread which struck me as being supportive of yours ideas of separation of fission and fusion days. Maybe they should add fusion)

 

"This is an update on my NR supplementation. 71 yo male, who has lost at least 50% of NAD due to ageing.   I have been taking 500 mg NR daily for 2 months.  Some days, I felt great and others I have a lot less energy.  When I first started the NR, got a big boost in energy, which has steadily gone down since then.  After consulting with some very knowledgeable people that are up on NAD+ supplementation, I have decided to go on a intermediate dosing schedule of 3 X week of 500 mg., and see how I feel.  There are many people that feel that once NAD+ has been boosted in the cell it stays at high levels for a few days.  It could be that NAD levels in the cell stay at a high levels 48-72 hours after supplementation with NR.

 

   Taking a look at what is happening in our cells, it seems logical that I would have lower energy and be tired from mitophagy when taking a daily dose as you have smaller and less mitochondria after removing damaged ones.  On this intermediate schedule, I would be going in periodically to clean out the damaged cells while boosting NAD+.  This schedule is very similar to taking Rapa once weekly.  One could do a half-life study on NR, but that doesn't tell you how much NAD is left in cell.  There are no good studies showing how long NAD+ stays in the cell after having been boosted by NR.  I know that there are other reasons for taking NR, but feel that mitophagy is the number one reason.   But I know how I feel and will keep track of that for a couple of months. "


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#446 Nate-2004

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Posted 03 October 2017 - 09:33 PM

 

For some time I believed that fission and fusion should be well separated. then more recently I began experimenting with daily fission/mitophagy with fusion/biogenesis inserted almost as an afterthought. Now I’m going back to my first idea—that these things ought to be well separated. This comes from my realization that it’s possible to increase mitochondrial mass far beyond what I expected, and mitochondrial mass (if healthy) is key to cellular health and potential rejuvenation of both the cells and the body.

 

Previously I referenced an in vitro experiment where cells exposed to elevated levels of lactate (10 mM) for three days showed an increase of mitochondria mass of 350% of control. (See Fig. 2C) This is interesting, if not astounding. Also interesting is that the NAD+/NADH ratio is inversely proportional to the lactate/pyruvate ratio (Fig. 2A). High lactate (and low NAD+) appears to be a strong signal for mitochondrial biogenesis. Thus exercise promotes health through all tissues by increasing blood levels of lactate/lactic acid. One minute of extreme exercise can pump up lactate to levels higher than the 10 mM of the in vitro cellular experiment for fifteen minutes (Fig. 6).  Similar levels can be achieved for hours by supplementation, but very high doses of lactate are needed. (See Chart 1, an experiment in rabbits where mg/cc of the y-axis can be converted to mM by multiplying by 11.)

 

 

So the bottom line:

 

1.    For the protocol, 3 or 4 days of fission, then 3 or 4 days of fusion, then at least one day off (esp. if stearic acid is used for fusion).

2.    For fusion/biogenesis, NAD+/NADH should be lowered and the lactate/pyruvate ratio raised (these are inversely linked), and thus the best lactate-raising exercise is high intensity for short periods.

3.    Adding several grams of lactate to the fusion/biogenesis stack is likely helpful.
 

 

Another takeaway from the first paper referenced above, is that the amino acid asparagine is as good as nicotinamide at reducing mito content in vitro.

 

 

 

The cytosolic conversion of NADH to NAD+ can be promoted by an increase in the concentration of aspartate, which can be achieved by the addition to the culture medium of asparagine that is readily converted to aspartate by cytosolic asparaginase (29). We treated cells with 20 mm asparagine or NAD+ (treatment included as a positive control), and the effects on the mitochondrial content and MMP were monitored. Treatment of Asn caused a decrease in the mitochondrial content, with the kinetics being similar to that induced by NAD+ or NAM. For 3 days, nearly 40% reduction in the mitochondrial content was observed in both cases of Asn and NAD+ (Fig. 2D).

 

https://www.ncbi.nlm...les/PMC3365962/

 

 

 

This is good stuff.

 

I wish I could do fission for 3 days but since I'm on keto, and insulin plays a role in the recycling of vitamin C, I should probably play it safe till after I go back on a more regular diet. I have to get a lot more vitamin C on keto so going 1.5 days at the most on fission is probably sufficient for now... or I might get scurvy or at best lose collagen.

 

I will definitely be doing more HIIT exercise on fusion days though and more of my bodyweight lifting on fission days (or just deadlifts if I can manage those). Doesn't lactate only build up in muscle when you exercise or other places as well?

 

I looked on Amazon, magnesium lactate is expensive.


Edited by Nate-2004, 03 October 2017 - 09:48 PM.


#447 Nate-2004

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Posted 04 October 2017 - 01:58 AM

I meant to ask regarding ATP, would creatine do anything to help if taken during fusion?



#448 Turnbuckle

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Posted 04 October 2017 - 11:06 AM

I don't know what creatine would do, so I encourage to try it both ways and report back.

 

As for my comments in post 438 above--

 

1.    For the protocol, 3 or 4 days of fission, then 3 or 4 days of fusion, then at least one day off (esp. if stearic acid is used for fusion).

 

 

 

 

Ultimately that day off should become several days, then weeks, then maybe months. The goal is to return the body to a more youthful state, and presumably cellular mito QC will return to a more youthful state as well. Then you can coast along as you did when you were younger.


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#449 Nate-2004

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Posted 04 October 2017 - 06:16 PM

Since lactic acid builds up during intense exercise, this leads me to conclude that Beta Alanine might be better on fission days, or avoided altogether, since this counters lactic acid build up... Unless I'm misunderstanding this. 

 

 


Out of the multiple mechanisms of systemic buffering (including proteins and amino acids, bicarbonate, and phosphates), carnosine contributes to intracellular buffering due to the imidazole structure of its histidine residue.[3] Large amounts of histidine dipeptides can be stored in cells with no apparent adverse effects. Theses stores explain why the synthesis or intake of beta-alanine, not histidine, is the rate-limiting step in the production of carnosine. The benefits of beta-alanine are highly associated with how much beta-alanine and carnosine (two buffering agents) are present in a muscle cell prior to contraction.[100]

Due to this buffering, beta-alanine can reduce acidosis without influencing oxygen uptake.[101]Although lactate (lactic acid) does not appear to inhibit muscular contraction per se, it is correlated. This may be due to an accumulation of H+ ions eventually inhibiting muscle contraction and glycolysis.[102] Many studies have noted that buffering acidity in vivo leads, via either direct or indirect mechanisms, to increases in performance in short-term high-intensity exercise.[103]

https://examine.com/...s/beta-alanine/

 

 


Edited by Nate-2004, 04 October 2017 - 06:17 PM.


#450 Heisok

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Posted 04 October 2017 - 10:32 PM

Turnbuckle, that is great news!!!!!! I think that at this stage, I can experiment with just the exercise protocol once a week.

 

Turbuckle wrote:

"As for my comments in post 438 above--

Quote

1.    For the protocol, 3 or 4 days of fission, then 3 or 4 days of fusion, then at least one day off (esp. if stearic acid is used for fusion).

 

 

Ultimately that day off should become several days, then weeks, then maybe months. The goal is to return the body to a more youthful state, and presumably cellular mito QC will return to a more youthful state as well. Then you can coast along as you did when you were younger."







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