LONGECITY

Maintaining the fasting/fusion detour a little longer: out walking today I wondered why do stem cells divide symmetrically under mitochondrial fusion? The has not been discussed, as far as I am aware.

 

It seemed quite obvious. Many of us know from experience the regenerative properties of fasting; indeed Longo observed that white blood cell counts drop off during fasting, as old cells are recycled for energy, but spike on refeeding (above pre-fasting levels) - the cause? Stem cells. To borrow from Cynthia Kenyon, we clearly possess this latent capacity to live longer under CR (and or possibly fasting), so fasting would of course represent something of a short-term gain if stem-cell pools were depleted during tough times, we'd wind up burning twice as bright but half as long, so symmetric differentiation would allow the body to service its need for rejuvenation during lean times but also retain a priori levels of stem cells. Additionally, it would make a lot of evolutionary sense for mitochondria  to fuse during fasting since, depleted of energy, a fusion boost would represent a critical advantage. The mitochondrial fused state then presumably signals symmetric differentiation.     

 

If true, then it shouldn't be a problem to retain a fused state for a few weeks at a time (unless say there is some periodic forced fission during fasting to maintain the plasticity mentioned important in the article a few posts back). Certainly, there are peaks and troughs in energy-levels during extended fasts. 

 

 

I addressed the fusion/self-renewal question with a reference in the first post, but here is more lengthy excerpt--

 

At the moment I am 20 hours without sleep, so with that in mind.

 

c60 isn't required for stem cells to differentiate symmetrically though, right? This was I thought I read from previous posts of yours a condition of fusion. C60 was used to drive the proliferation, to spend the stem cells accrued, to borrow your expression. Fusion, I'm sure I read from your posts, is the mitochondrial state which drives symmetric differentiation, the stem-cell pool increases, independently of c60. During fasting I assume, no trigger is required, the cells differentiate symmetrically and spend the excess. If this assumption is wrong I will (tomorrow) re-read the early posts to re-establish a hold on the theory. So apologies in advance.

 

My other rather simplistic observation when reading of a possible signalling role for ROS in the differentiation of stem cells (above) in the presence of c60, is the uber-ROS sponge that is c60oo.

 

Anyway, I'm out for the day and thanks for the reply. I've been feeling very energised with the few days on SA, creative and clear minded too. So my plan is to certainly force fission periodically, as you have suggested, but its a question of ratio. Its been a while since I underwent a fission/fusion protocol, but fission states weren't great from recollection. I skipped an SA day and began to feel pretty tired then took some more (in hot chocolate) and picked up pretty quickly.

At the moment I am 20 hours without sleep, so with that in mind.

 

c60 isn't required for stem cells to differentiate symmetrically though, right? This was I thought I read from previous posts of yours a condition of fusion. C60 was used to drive the proliferation, to spend the stem cells accrued, to borrow your expression. Fusion, I'm sure I read from your posts, is the mitochondrial state which drives symmetric differentiation, the stem-cell pool increases, independently of c60. During fasting I assume, no trigger is required, the cells differentiate symmetrically and spend the excess. If this assumption is wrong I will (tomorrow) re-read the early posts to re-establish a hold on the theory. So apologies in advance.

 

My other rather simplistic observation when reading of a possible signalling role for ROS in the differentiation of stem cells (above) in the presence of c60, is the uber-ROS sponge that is c60oo.

 

Anyway, I'm out for the day and thanks for the reply. I've been feeling very energised with the few days on SA, creative and clear minded too. So my plan is to certainly force fission periodically, as you have suggested, but its a question of ratio. Its been a while since I underwent a fission/fusion protocol, but fission states weren't great from recollection. I skipped an SA day and began to feel pretty tired then took some more (in hot chocolate) and picked up pretty quickly.

 

Normally stem cells are quiescent due to the large numbers of UCP2 pores that leak protons and eliminate ATP production. Stem cells shut down the leakage to wake up, and C60 appears to do that that for them.

Edited by Turnbuckle, 29 May 2019 - 11:43 AM.

Normally stem cells are quiescent due to the large numbers of UCP2 pores that leak protons and eliminate ATP production. Stem cells shut down the leakage to wake up, and C60 appears to do that that for them.

 

Thanks but presumably there is an endogenic process which achieves the same effect albeit not as scaled, such as during fasting, so how is that achieved?

Edited by ambivalent, 29 May 2019 - 01:03 PM.

Thanks but presumably there is an endogenic process which achieves the same effect albeit not as scaled, such as during fasting, so how is that achieved?

 

 

You tell me. I don't know of one.

Surely its improbable that additional stem cells generated under mitochondrial fusion would only be activated in the presence of c60. Why would any fusion stem-cell boon only be utilisable under c60 stimulation? Certainly it makes sense (to me) from your explanation, that there would be additional stem-cell activity under c60, but stearic acid should still encourage stem-cell proliferation just through triggering the mito-fusion state.

Surely its improbable that additional stem cells generated under mitochondrial fusion would only be activated in the presence of c60. Why would any fusion stem-cell boon only be utilisable under c60 stimulation? Certainly it makes sense (to me) from your explanation, that there would be additional stem-cell activity under c60, but stearic acid should still encourage stem-cell proliferation just through triggering the mito-fusion state.

 

Can you link us to evidence that mito fusion stimulates stem cells? 

No, I'm merely suggesting that if additional stem cells are produced during fusion then there must be a purpose to it beyond waiting for stimulation from c60 - why increase stem-cell supplies if they aren't going to be activated? If fusion occurs under fasting then this would seem a pretty good explanation since stem cells are utilised in or after the fasted state, as Longo demonstrated. There obviously must be an endogenous method to stimulate stem cells, it would be strange if there wasn't increased stem cell activation (at some point), subsequent to an environment which increased stem-cell production. 

 

Naturally, I'm not especially concerned about taking c60 (and am keener for dramatic effects), but I am short of recommending it, if taking stearic acid and or fission/fusion gets the job slowly then that I'd not need to worry about finding an utilising an accelerated method to activate stem cells for other people. 

Edited by ambivalent, 30 May 2019 - 01:02 PM.

No, I'm merely suggesting that if additional stem cells are produced during fusion then there must be a purpose to it beyond waiting for stimulation from c60 - why increase stem-cell supplies if they aren't going to be activated? If fusion occurs under fasting then this would seem a pretty good explanation since stem cells are utilised in or after the fasted state, as Longo demonstrated. There obviously must be an endogenous method to stimulate stem cells, it would be strange if there wasn't increased stem cell activation (at some point), subsequent to an environment which increased stem-cell production. 

 

Naturally, I'm not especially concerned about taking c60 (and am keener for dramatic effects), but I am short of recommending it, if taking stearic acid and or fission/fusion gets the job slowly then that I'd not need to worry about finding an accelerated method to activate stem cells for other people. 

 

 

One last try and then I'm done: fusion and fission only bias SC division to self renewal or differentiation, respectively, if the SCs are dividing for other reasons. They don't drive SC division. I used stearic acid fusion and N+R fission for around 9 months to clear out the defective mitochondria caused by statin use, and I never saw any evidence of stem cell activity from fusion alone.

No, I'm merely suggesting that if additional stem cells are produced during fusion then there must be a purpose to it beyond waiting for stimulation from c60 - why increase stem-cell supplies if they aren't going to be activated? If fusion occurs under fasting then this would seem a pretty good explanation since stem cells are utilised in or after the fasted state, as Longo demonstrated. There obviously must be an endogenous method to stimulate stem cells, it would be strange if there wasn't increased stem cell activation (at some point), subsequent to an environment which increased stem-cell production.

Naturally, I'm not especially concerned about taking c60 (and am keener for dramatic effects), but I am short of recommending it, if taking stearic acid and or fission/fusion gets the job slowly then that I'd not need to worry about finding an utilising an accelerated method to activate stem cells for other people.

I think we're getting a little confused here because of the discussion of fusion and fasting. Fasting is when the body doesn't have a ready supply of glucose, so it starts breaking down protein in the body for necessary amino acids, and burning stored fats. This is the process of autophagy (self-eating). This is the main mechanism by which CR extends life - by preferentially breaking down damaged organelles such as mitochondria, as well as all proteins produced by the cell, it means that each cell has less damaged contents at any given time. This woukd likely clear out damaged cells as well, but also keep stem cells healthier (although they're less exposed to metabolic damage then other cells they still have some). Fasting will involve both fission and fusion depending on exactly what the body is doing, but presumably fission is upregulated overall because this is the best opportunity to recycle mitochondria.

Both the stearic acid papers posted in this thread show in vitro and in vivo that it upregulates fusion, atleast in some cells. This is not surprising given stearic acid is recognised by the body as a fat energy source (whereas palmitic acid is not).

So eating is likely going to overall balance mitochondria torwards fusion, as ATP production will be prioritised, and stearic acid will increase this.

Fasting likely is the best time for upregulating fission, as your body will be in autophagy mode (hopefully), and Nicotinamide or other autophagy induces will increase this.

So I'd take stearic acid when you break your fast. The C60 will then cause more stem cells to divide then they otherwise would (Turnbuckles posted a paper showing this happens), hopefully with a bias to symmetrical division due to the stearic acid. Of course if the body needs to replace some cells there will be assymetric division as well.

One last try and then I'm done: fusion and fission only bias SC division to self renewal or differentiation, respectively, if the SCs are dividing for other reasons. They don't drive SC division. I used stearic acid fusion and N+R fission for around 9 months to clear out the defective mitochondria caused by statin use, and I never saw any evidence of stem cell activity from fusion alone.

 

I won't drag this out, I understand that fusion doesn't drive stem-cell differentiation, but it does as you've indicate bias stem-cell division towards renewal. But such a bias is unlikely to serve a purpose beyond an opportunity to bio-hack. I'm simply thinking that if the body produces more stem cells under certain conditions, it plans to use more stem cells (now or later) - why waste the additional resource, why would I have to worry about activating them exogenously?

 

The proof of the pudding, as you've demonstrated, is in the eating and I'll leave it there.

Thanks for the post QoL. Earlier in the thread I linked to an article which stated:

 

'The researchers found that restricting the worms' diet, or mimicking dietary restriction through genetic manipulation of an energy-sensing protein called AMP-activated protein kinase (AMPK), maintained the mitochondrial networks in a fused or 'youthful' state. In addition, they found that these youthful networks increased lifespan by communicating with organelles called peroxisomes to modulate fat metabolism.'

 

So, this is why I wondered whether the increase in stem cell self renewal resulting from fusion, was encouraged and so utilised by the fasting-state (which utilises stem cells to replace those purged).  

 

Anyhow, without additional research, I've nothing more to add.

 

Thanks for the post QoL. Earlier in the thread I linked to an article which stated:

 

'The researchers found that restricting the worms' diet, or mimicking dietary restriction through genetic manipulation of an energy-sensing protein called AMP-activated protein kinase (AMPK), maintained the mitochondrial networks in a fused or 'youthful' state. In addition, they found that these youthful networks increased lifespan by communicating with organelles called peroxisomes to modulate fat metabolism.'

 

So, this is why I wondered whether the increase in stem cell self renewal resulting from fusion, was encouraged and so utilised by the fasting-state (which does utilise stem cells to replace those purged).  

 

Anyhow, without additional research, I've nothing more to add.

Edited by ambivalent, 30 May 2019 - 02:49 PM.

Thanks for the post QoL. Earlier in the thread I linked to an article which stated:

'The researchers found that restricting the worms' diet, or mimicking dietary restriction through genetic manipulation of an energy-sensing protein called AMP-activated protein kinase (AMPK), maintained the mitochondrial networks in a fused or 'youthful' state. In addition, they found that these youthful networks increased lifespan by communicating with organelles called peroxisomes to modulate fat metabolism.'

So, this is why I wondered whether the increase in stem cell self renewal resulting from fusion, was encouraged and so utilised by the fasting-state (which does utilise stem cells to replace those purged).

Anyhow, without additional research, I've nothing more to add.

I'm a little bit skeptical of these results. There are plenty of papers showing that fused mitochondria are typical of an aged state. What AMPK actually does is signal a lack of energy. In the short term this would trigger mito biogenesis to try and make up for this lack. Which is my guess of what the researchers were seeing. But long-term health requires fission and likely CR or intermittent fasting would upregulate this to extend cellular and organism lifespan.

One question here is, if C60 block UCP pores to either differentiate/proliferate potential stem cells, isn't taking curcumin or food source carotenoids on the other direction of this protocol?

 

https://www.ncbi.nlm...pubmed/26362189

 

Vegetables contain a variety of carotenoid such as lutein and zeaxanthin, which some studies say they increase the expression of UCP1.

The half life of such carotenoids is long, like days. This seems to mean that not all of your diet can be in the same way as the proposed protocol claims because it is not healthy to restrict one side of one's diet.

Edited by Graviton, 05 June 2019 - 07:22 PM.

One question here is, if C60 block UCP pores to either differentiate/proliferate potential stem cells, isn't taking curcumin or food source carotenoids on the other direction of this protocol?

 

https://www.ncbi.nlm...pubmed/26362189

 

Vegetables contain a variety of carotenoid such as lutein and zeaxanthin, which some studies say they increase the expression of UCP1.

The half life of such carotenoids is long, like days. This seems to mean that not all of your diet can be in the same way as the proposed protocol claims because it is not healthy to restrict one side of one's diet.

 

 

As long as it's not UCP2, which stem cells have in abundance. 

Any thoughts as to whether SA should help with the recovery of a burn injury in a 19 year old person (I've ruled out c60)?
Edited by ambivalent, 08 June 2019 - 11:46 AM.

$31 per kilo for c-18 doesn’t seem bad
https://www.scbt.com...c-acid-57-11-4/

$31 per kilo for c-18 doesn’t seem bad
https://www.scbt.com...c-acid-57-11-4/

 

No information about the purity. It seems that the CoA is available once the lot number is known.

No information about the purity. It seems that the CoA is available once the lot number is known.

I am going to try some.

I have been waiting awhile for a recommendation.

I'm going to assume it is safe to ingest.

Please someone summarize the last 31 pages of this topic so far?

Please someone summarize the last 31 pages of this topic so far?

 

A link to the latest protocol can always be found on my profile page.

My present thinking on this protocol is summarized below—

 

2. Filling stem cell pools produces a noticeable improvement in youthfulness, but overfilling them produces no further apparent improvement. Old cells don’t die just because new cells are available. With a pseudo-geometric progression of stem cells via fusion/C60 treatment, just a few cycles of the stem cell protocol may be all that is necessary. Three will make a difference (though it might take weeks to see it), and there may be no further improvement after a few dozen.

 

 

Hi,

 

I'm new here.  I took C60 at the advice of an acquaintance, 5ml every day from 4/2/19 - 5/16/19.  I abruptly stopped after reading about your theory (hypothesis?) that taking c60 likely depletes stem cell pools.  Taking c60 changed my life, all for the better, and I would like to start taking it again.  As a caution against stem cell depletion, I'd like to try your stem cell renewal protocol.  (I'm over 60)

 

My question is:  Do you take C60 only on the days of fusion?  Only on the days that you also take stearic acid?  If you're recommending just a few cycles, what happens after those cycles are completed?  Do you go back to taking c60 daily until such time that you feel another round of stem cell rejuvenation is necessary?

 

Thanks for your contributions here.

V

Hi,

 

I'm new here.  I took C60 at the advice of an acquaintance, 5ml every day from 4/2/19 - 5/16/19.  I abruptly stopped after reading about your theory (hypothesis?) that taking c60 likely depletes stem cell pools.  Taking c60 changed my life, all for the better, and I would like to start taking it again.  As a caution against stem cell depletion, I'd like to try your stem cell renewal protocol.  (I'm over 60)

 

My question is:  Do you take C60 only on the days of fusion?  Only on the days that you also take stearic acid?  If you're recommending just a few cycles, what happens after those cycles are completed?  Do you go back to taking c60 daily until such time that you feel another round of stem cell rejuvenation is necessary?

 

Thanks for your contributions here.

V

 

Hi Vivian, 

 

Yes, a key part of this protocol is to take C60 while in a state of fusion, and that state of fusion is induced by consuming stearic acid  - either in a brownie or in hot chocolate with lecithin. Stearic acid has some tricky absorption issues, so I suggest you read through the thread to pick up the details of consuming stearic acid. 

 

I believe Turnbuckle has stated that he recommends multiple cycles of the stem cell renewal protocol (perhaps around a dozen?), paired with the senescent cell clearance protocol, until you stop noticing benefits. At this point your stem cell pools may be full (we currently have no way to know for sure).

 

Once you reach this point, you can continue with a maintenance protocol. This maintenance protocol consists of regularly taking the senescent cell clearance protocol alongside occasional consumption of threonine to feed the stem cells. 

 

I believe you could also continue to take c60 by itself after this point, but you would want to do so responsibly, since c60 by itself would be drawing upon your stem cell pools. You can always top off your stem cell  pools with the stem cell renewal protocol as needed. 

 

 

Can you tell us a bit more about the types of effects you have noticed from your c60 consumption? 

A link to the latest protocol can always be found on my profile page.

Is that the latest?

Time 0 —

Stearic acid* (120 mg/kg)  — 10 g
Liposomal glutathione — 1 g
SAM-e — 200 mg

  

Time 3:00 —

Leucine** — 5-10 g

Curcumin** phytosome — .5-1 g

Threonine — 10 g

PQQ — 20mg

Liposomal glutathione — 1 g

C60 — 3 mg (in EVOO or MCT oil) 

 

Where do you order all the ingredients?  Do you have links by any chance?

Is that the latest?

Time 0 —

Stearic acid* (120 mg/kg)  — 10 g
Liposomal glutathione — 1 g
SAM-e — 200 mg

  

Time 3:00 —

Leucine** — 5-10 g

Curcumin** phytosome — .5-1 g

Threonine — 10 g

PQQ — 20mg

Liposomal glutathione — 1 g

C60 — 3 mg (in EVOO or MCT oil) 

 

Where do you order all the ingredients?  Do you have links by any chance?

 

Everything except C60 can be purchased from Amazon.

C60 from SESRES: https://www.sesres.c...powder/#buy_c60

 

Actually even C60 is on sale on Amazon (by SESRES): https://www.amazon.c...t/dp/B07CV7MFDF

Edited by aribadabar, 12 July 2019 - 01:23 PM.

Anybody researched the best price / quality etc....
Wonder where Turnbuckle gets his?

A link to the latest protocol can always be found on my profile page.

 

I would just like to thank you Turnbuckle, on behalf of myself and other Longecity users you have helped, for the excellent and well researched protocols you have created. You have created some really beneficial innovations and have been kind enough to share them with all of us at Longecity. As if that was not enough, you have also been very generous in your time by responding to so many questions in these threads. Thanks a bunch!!

Hi Vivian, 

 

Yes, a key part of this protocol is to take C60 while in a state of fusion, and that state of fusion is induced by consuming stearic acid  - either in a brownie or in hot chocolate with lecithin. Stearic acid has some tricky absorption issues, so I suggest you read through the thread to pick up the details of consuming stearic acid. 

 

I believe Turnbuckle has stated that he recommends multiple cycles of the stem cell renewal protocol (perhaps around a dozen?), paired with the senescent cell clearance protocol, until you stop noticing benefits. At this point your stem cell pools may be full (we currently have no way to know for sure).

 

Once you reach this point, you can continue with a maintenance protocol. This maintenance protocol consists of regularly taking the senescent cell clearance protocol alongside occasional consumption of threonine to feed the stem cells. 

 

I believe you could also continue to take c60 by itself after this point, but you would want to do so responsibly, since c60 by itself would be drawing upon your stem cell pools. You can always top off your stem cell  pools with the stem cell renewal protocol as needed. 

 

 

Can you tell us a bit more about the types of effects you have noticed from your c60 consumption? 

 

Thanks for your reply.  I appreciate your input.

 

I've read through this thread several times.  Regularly taking the senescent cell clearance protocol after stem cells are deemed to be "full" is not something I remember reading here.....hmm.  Is there a post(s) I missed?  Or maybe further information on other threads?

 

The effects I noticed while taking C60:  Mood, energy, stamina much improved. Sleep better, more restorative.  Hypo-thyroid medication was slashed.  Medication for post nasal drip no longer necessary.  Balance improved.  Skin overall much younger-looking.  Troublesome mole/old scars disappeared. 

 

After quitting C60, all the wonderful effects cascaded as quickly as they came on (darn) The only changes that seemed to stick are, the mole/old scars have stayed away.  My TSH slightly hyper with the lower medication 6 weeks after discontinuing C60. Whatever thyroid repair was done while taking C60, seemed to have stuck 6 weeks out.

 

So, my journey has been, 6 weeks on C60 and loving it.  Then 6 weeks off C60 and not loving it....  Now in middle of 2nd cycle of SC renewal protocol, and I'm back to loving it.  Mood, energy and stamina being the 3 big difference-makers for me.

 

 

 

 

 

I wonder if we might achieve a MUCH stronger senolytic action by combining fission with Azithromycin and Doxycycline. It's used here for cancer, but given the mechanism is simultaneously inhibiting Mt DNA synthesis (synergistic combination of antibiotics' off target effects) and encouraging mitochondrial biogenesis (used high dose Vit C in the paper, but I bet nicotinamide plus maybe resveratrol would be effective), I expect it would be very effective for senescent cell clearance.

https://www.ncbi.nlm...07/#!po=35.7955

Azithromycin has been touted (by same authors) as a Senolytic before, but required concentration always looked prohibitive to me. But with the combination with Doxycycline, this is solved.

Anyone dare try it?

Thanks for your reply.  I appreciate your input.

 

I've read through this thread several times.  Regularly taking the senescent cell clearance protocol after stem cells are deemed to be "full" is not something I remember reading here.....hmm.  Is there a post(s) I missed?  Or maybe further information on other threads?

 

The effects I noticed while taking C60:  Mood, energy, stamina much improved. Sleep better, more restorative.  Hypo-thyroid medication was slashed.  Medication for post nasal drip no longer necessary.  Balance improved.  Skin overall much younger-looking.  Troublesome mole/old scars disappeared. 

 

After quitting C60, all the wonderful effects cascaded as quickly as they came on (darn) The only changes that seemed to stick are, the mole/old scars have stayed away.  My TSH slightly hyper with the lower medication 6 weeks after discontinuing C60. Whatever thyroid repair was done while taking C60, seemed to have stuck 6 weeks out.

 

So, my journey has been, 6 weeks on C60 and loving it.  Then 6 weeks off C60 and not loving it....  Now in middle of 2nd cycle of SC renewal protocol, and I'm back to loving it.  Mood, energy and stamina being the 3 big difference-makers for me.

 

 

Hi Vivian, 

 

Go here to see Turnbuckle's senescent cell clearance protocol: https://www.longecit...ndpost&p=866728

 

The C60 effects you listed are very interesting. Were you suffering from hashimoto's thyroiditis by any chance? 

 

Since you have become mildly hyperthyroid while on your new reduced dose of thyroid medication, I'm cautiously optimistic that the protocol may have repaired damage to your thyroid. That would be incredible. 

 

Keep in mind that C60's mechanism of action is still speculative but can be boiled down to three main parts: (1) stem cell stimulation, (2) anti-oxidant/ anti-inflammatory, and (3) immunomodulatory.

 

Each effect appears to have a different duration in the human body.   The rejuvenation that results from the stimulation of stem cells is long lasting, while the anti-oxidant, anti-inflammatory, and immunomodulating effects are short term and eventually fade away after you stop consuming C60. For anti-aging purposes, the stem cell effect is the  most important, and this is paired with the senescent cell protocol to maximize age reversal. In your case, since it sounds like you suffer from inflammatory issues, effects 2 and 3 listed above may be most important for your current quality of life. This means that the senescent cell protocol may not be as important for you, and you may benefit from more frequent consumption of C60 than Turnbuckle. Turnbuckle appears to be using C60 exclusively for age reversal, which means he doesn't need to take C60 all that often once he has refilled his stem cell pools. By contrast, your inflammatory symptoms clearly return once you stop taking C60, so you may want to establish a regular intermittent dosing protocol of C60, while occasionally refilling your stem cell pools with Turnbuckle's protocol. Current best practice is to take C60 intermittently, rather than everyday. If at some point you want to pursue age reversal more aggressively, then you could add in the senescent cell protocol. 

 

Also, please bear in mind that none of the above is "medical advice." 

 

I hope this helps!