2523 replies to this topic

[Turnbuckle]

Talk about deja vu!  Here are some quotes from "C60 Toxicity Concerns" from 2016 where the question of the spacing of niacinamide and C60 consumption came up:

 

 

 

 

 

 

 

How much spacing between the C60 and niacinamide is optimal? Might the present protocol be cutting it a little too close for those of us using commercial C60 oils? Would there be any cost to delaying the fission until 36 or even 48 hours after the C60?  

 

These days I use fusion/proliferation on day one, then fission/differentiation on days 2-4. I then allow a week or more before the next round.

[Empiricus]

These days I use fusion/proliferation on day one, then fission/differentiation on days 2-4. I then allow a week or more before the next round.

 

Leaving a week or more between protocols addresses the problem of the NR/N+R remaining for over 24 hours.  (Although this issue remains something people like me who regularly take B-complex, NAD+ supplements, or even multivitamins might want to be vigilant about).

 

However, it doesn't address the likelihood of C60 persisting in the body well into Day 2 after you've taken the niacinamide (as per the protocol). Can you see any issues that might arise if the fission day is put off significantly longer?  For example:

 

Day 1 - fusion

Day 2 - break (or fission supplements other than niacinamide)

Day 3-5 - fission with N+R

Edited by Empiricus, 15 July 2022 - 12:59 PM.

[Empiricus]

This post of mine from 2016 recounts possible adverse effects from having taken C60 in too close proximity to NR.  What it showed was that 

- 2 weeks between C60 and NR = very good results

- 2.5 days between C60 and NR = bad results

Based on this data, and my more recent experience that 1 day is not at all sufficient, I'm thinking perhaps I should do fusion on Day 1 and fission on Days 7-9.   Is there any reason to believe stretching it out this much wouldn't accomplish much the same thing as a more compact protocol?

 

Edited by Empiricus, 15 July 2022 - 02:14 PM.

[resveratrol_guy]

Turnbuckle, one thing I don't understand is how this SC protocol interacts with your fission/fusion protocol. You've mixed references to both in this thread, and it's not clear if they're running in parallel or intermittantly in series. What schedule do you use?

 

Also, the brownie step seems rather complicated and labor-intensive. I personally have no problem with foul-tasting supplements that are worth taking, so is there are a shorter version (with a dosing latency shorter than 3 hours, for that matter) if one uses GMS instead of stearic acid, and just throws everything into a blender instead of making brownies?

 

By the way, I assume that alpha ketoglutarate is equivalent to alpha ketoglutaric acid, yes?

 

Finally, what does the C60 really contribute, considering that the stearic acid or GMS should do the heavy lifting for fusion? Does it merely block mitochondrial pores and thus enhance energy for a couple of days? Or is there some deeper connection to SCs? I seem to recall a theory that it's a fusion promoter in its own right, but is that really needed here in light of the other ingredients? To put it another way, what would one lose by eliminating it from the protocol? Just some temporary performance boost that one could get from NMN, for example? Or something more?

[Turnbuckle]

Turnbuckle, one thing I don't understand is how this SC protocol interacts with your fission/fusion protocol. You've mixed references to both in this thread, and it's not clear if they're running in parallel or intermittantly in series. What schedule do you use?

 

Also, the brownie step seems rather complicated and labor-intensive. I personally have no problem with foul-tasting supplements that are worth taking, so is there are a shorter version (with a dosing latency shorter than 3 hours, for that matter) if one uses GMS instead of stearic acid, and just throws everything into a blender instead of making brownies?

 

By the way, I assume that alpha ketoglutarate is equivalent to alpha ketoglutaric acid, yes?

 

Finally, what does the C60 really contribute, considering that the stearic acid or GMS should do the heavy lifting for fusion? Does it merely block mitochondrial pores and thus enhance energy for a couple of days? Or is there some deeper connection to SCs? I seem to recall a theory that it's a fusion promoter in its own right, but is that really needed here in light of the other ingredients? To put it another way, what would one lose by eliminating it from the protocol? Just some temporary performance boost that one could get from NMN, for example? Or something more?

 

If C60 were a fusion agent, then you would not need another one. But clearly it isn't, as the Moody group discovered with they tried to repeat the rodent experiment. C60 failed to do anything re life extension. Blocking the pores of quiescent SC mitochondria with C60 wakes them up, and when they wake up they will either differentiate or proliferate. A state of fusion directs them to the latter, which increases their numbers. A state of fission is required for apoptosis of senescent cells that you want to replace.

 

For fusion, GMS is fine, and DHM is fine. DHM has the advantage of penetrating the BBB.

[Turnbuckle]

This post of mine from 2016 recounts possible adverse effects from having taken C60 in too close proximity to NR.  What it showed was that 

- 2 weeks between C60 and NR = very good results

- 2.5 days between C60 and NR = bad results

Based on this data, and my more recent experience that 1 day is not at all sufficient, I'm thinking perhaps I should do fusion on Day 1 and fission on Days 7-9.   Is there any reason to believe stretching it out this much wouldn't accomplish much the same thing as a more compact protocol?

 

Those were the days before we began using fusion, so probably not relevant.

[Empiricus]

Those were the days before we began using fusion, so probably not relevant.

 

With the exception of the fusion day of Cycle 3, my first three cycles on this protocol were not particularly pleasant, and my experience points to the most likely explanation being the spacing of the C60 and niacinamide.  The potential for nasty interactions between C60 and NAD+ supplements were discussed on this forum several years ago. (I had forgotten all about this risk, even though I had posted about it back in the day.)

 

Anyway, the experiences of anyone who took C60 and NAD+ supplements--whether taken together or spaced out by hours or days--ought to be relevant to preventing reoccurrence of the setback I experienced, whether or not they had used fusion.  

 

For example, here's another case report from the "pre-fusion days" I came across just today:  

 

I forgot to mention I'm doing niacin/C60 cycles like Turnbuckle's protocol. I'm taking 3-4gr niacin daily (I'm a severe overmethylator) and when I plan to take C60 I stop taking it for 24 hours, then I take the C60 and I don't take again niacin after 36-48h (if I do it I get a bad reaction).

 

Gestur found that after dosing C60, he needed to wait at least 36-48 hours before taking niacin to avoid "a bad reaction."  

 

Turnbuckle's current protocol establishes Day 1 for fusion, followed by Days 2-4 for fission. Would this work for Gestur? Doesn't sound like it to me.

 

Nevertheless, Turnbuckle has documented success taking niacinamide within 24 hours of taking C60 with fusion. Likely one reason it's working for Turnbuckle is that older people have less NAD+, and so supplemental N+R compensates for their natural deficit, meaning there is less NAD+ available to form theorized toxic adjuncts with C60.  

 

There are no studies proving how long C60 persists in humans. So for many of us, to know how soon it's OK to take NAD+ supplements, it will be helpful to examine a variety of reported experiences. 

 

C60EVOO and Nicotinamide Riboside interaction

https://www.longecit...de-interaction/

 

Nicotinamide Riboside and C60 Olive oil dosage help

https://www.longecit...il-dosage-help/

Edited by Empiricus, 16 July 2022 - 07:14 PM.

[resveratrol_guy]

If C60 were a fusion agent, then you would not need another one. But clearly it isn't, as the Moody group discovered with they tried to repeat the rodent experiment. C60 failed to do anything re life extension. Blocking the pores of quiescent SC mitochondria with C60 wakes them up, and when they wake up they will either differentiate or proliferate. A state of fusion directs them to the latter, which increases their numbers. A state of fission is required for apoptosis of senescent cells that you want to replace.

 

For fusion, GMS is fine, and DHM is fine. DHM has the advantage of penetrating the BBB.

 

Thanks, Turnbuckle. I guess the next question would be: do we need to awaken the SCs at all? What if we don't? Will they still proliferate sufficiently well? What I'm getting at is this: is it possible to drop C60 and still have a useful regimen, albeit one that shows effects over a longer period of time?

 

I'm also still wondering how you schedule this regimen with your fission/fusion protocol. They sound so functionally similar, yet have a rather different bill of materials.
 

[Turnbuckle]

Thanks, Turnbuckle. I guess the next question would be: do we need to awaken the SCs at all? What if we don't? Will they still proliferate sufficiently well? What I'm getting at is this: is it possible to drop C60 and still have a useful regimen, albeit one that shows effects over a longer period of time?

 

I'm also still wondering how you schedule this regimen with your fission/fusion protocol. They sound so functionally similar, yet have a rather different bill of materials.
 

 

You need to wake them up. As for the mito protocol, I suggest doing that one first.

[resveratrol_guy]

You need to wake them up. As for the mito protocol, I suggest doing that one first.

 

OK so we still need C60. But what does it mean to do the mito protocol first? What's the schedule? 3 days of mito fission, one day of mito fusion, a week of break, then this other completely different definition of fission and fusion? (We need some separate vocabulary so as not to confuse fission with fission and fusion with fusion.) And how many reps of each, etc?

 

Scheduling is paramount. As with any regimen, doing it too often or not often enough is a serious problem. Please provide some details, even though I'm sure we all realize that it's subject to future optimization.

Edited by resveratrol_guy, 17 July 2022 - 03:54 PM.

[kurt9]

It would make sense to do the mito protocol first as this protocol would work better with functional mitochondria.

[Turnbuckle]

OK so we still need C60. But what does it mean to do the mito protocol first? What's the schedule? 3 days of mito fission, one day of mito fusion, a week of break, then this other completely different definition of fission and fusion? (We need some separate vocabulary so as not to confuse fission with fission and fusion with fusion.) And how many reps of each, etc?

 

Scheduling is paramount. As with any regimen, doing it too often or not often enough is a serious problem. Please provide some details, even though I'm sure we all realize that it's subject to future optimization.

 

 

The mito protocol can be found on another thread. See: https://www.longecit...ndpost&p=903440

[Kelvin]

I would avoid blueberries because they contain pterostilbene.

Pterostilbene belongs to the resveratrol family of compounds. Resveratrol’s effect on telemorase can rescue older cells that are approaching senescence but this protocol is better used if older cells are pushed into senescence a bit earlier than normal so that senolytics induce apoptosis and Newly created stem cells can take their place.

But not too rapidly. If too many older cells are pushed into senescence at once there might be too many openings for stem cells to find target cells to replace them.

I used 300 mgs of fisetin on 1 C60 fission day, per cycle, to give apoptosis an extra jolt on any aging cells I had.

If people are having issues with niacin or nicotinamide perhaps they should use NMN as their NAD+ booster?

I have been using NR-chloride and NMN (UltraHealth brand) for 3 years as my NAD+ boosters with no niacin-flush like symptoms.

[johnhemming]

I did not know that blueberries contain pterostilbene.  However, I personally take pterostilbene in preference to resveratrol.   Resveratrol is a cox-1 inhibitor which I consider to be a bad thing.

 

My view on senescence is that getting cells to function properly is better than killing them off.  Some cells are partially senescent or dedifferentiated and I would prefer that they were properly differentiated.

 

 

[Kelvin]

Suit yourself but you may want to take pterostilbene when not on the cycle because the purpose of the protocol is at odds with preserving older cells.

I’m not sure what role, if any, anthocyanins could play. But if one is looking for a high source of anthocyanins then the best supplement source is the aronia berry species aronia melanocarpa.

Aronia has by far the most anthocyanin content of any other type of berry. It also tastes great.

[Turnbuckle]

My view on senescence is that getting cells to function properly is better than killing them off.  Some cells are partially senescent or dedifferentiated and I would prefer that they were properly differentiated.

 

 

Then you will not be interested in the protocols of this thread. 300 billion cells are replaced every day, and the techniques presented here are directed to improving that maintenance process.

[johnhemming]

I do intend to try this protocol when I have finished testing various other things (which are currently going well).   My current test results appear to imply that cells are re-entering the cell cycle if badly rather than dying off.

 

Cells last varying times

https://www.sciencef...ve-the-longest/

 

"On average, the cells in your body are replaced every 7 to 10 years. But those numbers hide a huge variability in lifespan across the different organs of the body."

 

Which to me implies that it is best to try to ensure a cell functions rather than killing it off even if killing of cells is better than leaving cells to poison other cells with IL-10.

[johnhemming]

I’m not sure what role, if any, anthocyanins could play. But if one is looking for a high source of anthocyanins then the best supplement source is the aronia berry species aronia melanocarpa.

Aronia has by far the most anthocyanin content of any other type of berry. It also tastes great.

There is an argument that Ferulic acid is the active metabolite from the anthocyanin pathway.  I take that ... and pterostilbene. 

[Kelvin]

What is debatable is how frequently the C60 protocol should be used based on age and any preexisting health problems.

Frequency should be a function of how full stem cell pools are and what percent of the body consists of aged (or damaged) cells.

In theory the older one is the more frequently one should use the protocol because they have more aged cells that need to be replenished with any available stem cells. Of course this is a simplification because different cells have different lifespans, but I’m just doing a back of the envelope calculation here.

BUT it may not need to be very frequent even for the elderly because the protocol doubles stem cell pools with every cycle until the pool reaches 100% capacity. Also, no pool can exceed 100% capacity without the surplus stem cells being destroyed by homeostatic mechanisms.

Exponential growth means that a stem cell pool at 1% capacity would only need 6 cycles to reach 64% capacity and a 7th to hit 100%.

Lets say that only 6 to 10 cycles are needed to get an elderly persons available stem cell pools up to 100% full.

Then how often would they need to use C60 to replenish their pools to 100%?

There wouldn’t be much point using the cycle if the pools are depleted to 90% because they cannot be doubled to 180% capacity. The person would be better off waiting until the pools dipped below 50% and then taking 1 or 2 cycles to bring it back to 100%.

Maybe they could judge when they are in need of another cycle if they see their skin begin to age since skin cells use stem cells more rapidly than other types of cell?

[Kelvin]

Potentially even those over 65 might not need to use the cycle more than once or twice a year.

In my case I am still noticing measurable, ongoing health improvements from the 6 C60 cycles I tried for the first time ever in February and March of this year. Caveat is that I am only 42.

These are in addition to the other health benefits I had written about previously such as reduced sleep requirements.

Four months later I am still seeing weekly, gradual, improvements to my skin smoothness. Right now my skin looks like it did in my early 30s. Wound healing times have been reduced significantly and I am seeing older scars start to smooth and fade.

I noticed 18 months ago rapidly graying hair. As of today my gray hairs look they have been reduced by at least two thirds, possibly more like a reduction in grayness of 75%.

I also can keep building more muscle than ever before. My body type is ectomorphic and I never could buildup much bicep, abdominal, or pectoral strength.

But now my normal routine of weight training once or twice a week is improving my athletic build without any other changes.

My biceps can keep more muscle mass and my pecs and abs are more toned than ever, even compared to my 20s, without any additional exercise.

This has given me a leaner, more athletic look than I have ever had.

These ongoing benefits make me think that I do not to refill the pools until they dip below 50%. Instead it may only be neccessary for me to take senolytics by themselves to clear out any aged cells.

Of course, once again, someone older than me might require a more frequent useage.

[johnhemming]

Wound healing is a useful test.  Because I do weekly blood tests I can monitor how quickly the needle puncture disappears and to what extent there is any scarring.   I think this works as a measurement for any protocol that has real effects.

 

 

[Kelvin]

Surprisingly, it took longer to notice skin improvements than for the other benefits which were obvious early on.

More youthful skin only became apparent over the last two to three weeks.

Initially, when I was underwhelmed by how my skin looked, I tried to accelerate apoptosis with of the senolytics supplements and more fisetin.

But senolytics didn’t seem to hurry the process along either. Apparently at 42 I didn’t have enough aged cells that could be kicked into apoptosis by senolytic supplements.

Now I can see that skin cells are being created from the extra reservoir of stem cells I created months ago.

I’m going to refrain from restarting the C60 protocol for a few more months to test if the reserves dry up, or if the benefits seems like it can keep going with what I already created with C60.

If the gains holdup then I may only need to do 1 cycle every 6 months or per year to keep my stem cells pools full.

[Female Scientist]

Is anyone using this company for their epigenetic testing? I’m looking around for the best price for the quality test we need to monitor progress on Turnbuckle’s protocol. I see reference on this thread to 2 other testing companies but this one seems cheaper. Anyone with insight into this? https://epiagingusa.com/

[Turnbuckle]

Is anyone using this company for their epigenetic testing? I’m looking around for the best price for the quality test we need to monitor progress on Turnbuckle’s protocol. I see reference on this thread to 2 other testing companies but this one seems cheaper. Anyone with insight into this? https://epiagingusa.com/

 

The Trume TruAge test has gone up by $10 to $110, but is still cheaper.

[Bike_to_120]

Whew! Just read all 1884 posts!

 

I was looking into placental stem cell treatments and the high cost got me searching when I found this thread. I have degenerated discs in my neck and jaw and thought that stem cells may help. It seems that most of the focus here has been on epigenetic age reduction so I am not sure if this will work, but the price is right!

 

I am 69 and except for the disc issues, in very good health. Been taking intermittent doses of rapamycin the last 3 years which had a profound effect on kidney function, and lowered my epigenetic age 12 years. I measure about 20 biometrics daily as well as twice yearly full blood workups.

BP 104/64

BG 84

BMI 19

I mountain bike and hike quite a bit and if not for chronic neck/jaw pain I feel like I'm 30.

 

If anyone has had improvements with degenerated discs, I'd appreciate knowing.

thanks

[Turnbuckle]

Whew! Just read all 1884 posts!

 

I was looking into placental stem cell treatments and the high cost got me searching when I found this thread. I have degenerated discs in my neck and jaw and thought that stem cells may help. It seems that most of the focus here has been on epigenetic age reduction so I am not sure if this will work, but the price is right!

 

I am 69 and except for the disc issues, in very good health. Been taking intermittent doses of rapamycin the last 3 years which had a profound effect on kidney function, and lowered my epigenetic age 12 years. I measure about 20 biometrics daily as well as twice yearly full blood workups.

BP 104/64

BG 84

BMI 19

I mountain bike and hike quite a bit and if not for chronic neck/jaw pain I feel like I'm 30.

 

If anyone has had improvements with degenerated discs, I'd appreciate knowing.

thanks

 

I blew out a disk about twenty years ago,  and the pain was always there. About 2-3 years after beginning the protocol, it disappeared. So you can expect improvement, but it won't be as fast as some other changes.

[Kelvin]

Whew! Just read all 1884 posts!

I was looking into placental stem cell treatments and the high cost got me searching when I found this thread. I have degenerated discs in my neck and jaw and thought that stem cells may help. It seems that most of the focus here has been on epigenetic age reduction so I am not sure if this will work, but the price is right!

I am 69 and except for the disc issues, in very good health. Been taking intermittent doses of rapamycin the last 3 years which had a profound effect on kidney function, and lowered my epigenetic age 12 years. I measure about 20 biometrics daily as well as twice yearly full blood workups.
BP 104/64
BG 84
BMI 19
I mountain bike and hike quite a bit and if not for chronic neck/jaw pain I feel like I'm 30.

If anyone has had improvements with degenerated discs, I'd appreciate knowing.
thanks

Given your circumstances you may want to avoid using the senolytic and fission part of the protocol for the first few cycles. Fission will destroy damaged cells, but since you probably have a larger amount of disc damage fission would end up destroying more than stem cells would have time to replace.

The damaged cells would be useful to serve as targets for a restored stem cell poll to send in reserves. As time goes on you could gradually introduce fission supplements to speed on the process. Just don’t rush with introducing fission.

[Kelvin]

One other thing is to get a large supply of lysine and methionine because you will be using a lot of them on the protocol to feed the new stem cells.

When Turnbuckle said not taking lysine and methionine would lead to drowsiness he wasn’t joking.

I would say have at least 500 capsules of lysine (500 mgs per cap) and the same number and dose of methionine capsules on hand before you start.

[Empiricus]

Given your circumstances you may want to avoid using the senolytic and fission part of the protocol for the first few cycles. Fission will destroy damaged cells, but since you probably have a larger amount of disc damage fission would end up destroying more than stem cells would have time to replace.

The damaged cells would be useful to serve as targets for a restored stem cell poll to send in reserves. As time goes on you could gradually introduce fission supplements to speed on the process. Just don’t rush with introducing fission.

 

In the past, I suspect my use of fisetin, a senolytic, may have made an injury worse and not supported its recovery.  So avoiding senolytics until an injury is repaired makes sense to me. I described this possible side-effect of fisetin here and here. 

 

But I'm uncertain why the same precaution would apply to fission. I've never perceived such an issue with fission.  After all, fission eliminates weak mitochondria and I imagine it isn't helpful for cells of any age to keep these around.

Edited by Empiricus, 21 July 2022 - 12:12 PM.

[Turnbuckle]

In the past, I suspect my use of fisetin, a senolytic, may have made an injury worse and not supported its recovery.  So avoiding senolytics until an injury is repaired makes sense to me. I described this possible side-effect of fisetin here and here. 

 

But I'm uncertain why the same precaution would apply to fission. I've never perceived such an issue with fission.  After all, fission eliminates weak mitochondria and I imagine it isn't helpful for cells of any age to keep these around.

 

 

Fission does more than expose damaged mtDNA to QC. It's also necessary for apoptosis.

 

Prior to, or simultaneous with, cytochrome c release and upstream of caspase activation, mitochondria fragment into multiple small units. Blocking of this mitochondrial fission inhibits cytochrome c release and delays cell death, linking the morphogenesis machinery of this organelle to cell death induction.

https://www.ncbi.nlm...les/PMC2732420/

 

 

However, fission is also necessary for stem cell differentiation and replacement of senescent cells. Niacinamide improves knee pain for instance, likely via such a process of apoptosis and replacement.

 

Conclusion: This study indicates that niacinamide may have a role in the treatment of osteoarthritis. Niacinamide improved the global impact of osteoarthritis, improved joint flexibility, reduced inflammation, and allowed for reduction in standard anti-inflammatory medications when compared to placebo. More extensive evaluation of niacinamide in arthritis is warranted.

https://pubmed.ncbi....ih.gov/8841834/

 

 

From my own experience of being injured by fission/resveratrol and by fission/quercetin + Azithromycin and another antibacterial, I don't use senolytics anymore, just nicotinamide plus ribose. I expect that removing too many cells at one time is the problem. Azithromycin by itself can be very efficient--

 

As a consequence of this streamlined screening strategy, we identified Azithromycin and Roxithromycin as two novel clinically-approved senolytic drugs. However, Erythromycin – the very closely-related parent compound – did not show any senolytic activity, highlighting the dramatic specificity of these interactions. Interestingly, we also show that Azithromycin treatment of human fibroblasts was indeed sufficient to strongly induce both aerobic glycolysis and autophagy. However, the effects of Azithromycin on mitochondrial oxygen consumption rates (OCR) were bi-phasic, showing inhibitory activity at 50 μM and stimulatory activity at 100 μM. These autophagic/metabolic changes induced by Azithromycin could mechanistically explain its senolytic activity. We also independently validated our findings using the xCELLigence real-time assay system, which measures electrical impedance. Using this approach, we see that Azithromycin preferentially targets senescent cells, removing approximately 97% of them with great efficiency. This represents a near 25-fold reduction in senescent cells. 

 

 

Removing is one thing. Replacing them properly during a wholesale removal is another. Removing them too fast may cause injury by overwhelming the system.