331 replies to this topic

[solarfingers]

With regard to the possibility that C60 is promoting stem cell differentiation--from reports of the disappearance of scars, the regrowth of hair, and the apparent re-stimulation of a knee injection of stem cells--there isn't any obvious reason why C60 would also promote stem cell proliferation. And you need both proliferation and differentiation otherwise you could deplete them. So my protocol is now a single dose of C60 a week, and during the off days, several doses of supplements that promote proliferation. These are fucoidan, l-theanine, and blue-green algae, along with the astragalus I was already taking.

There are stem cell stimulating supplements on the market that contain these ingredients and others, but I am avoiding them because they contain resveratrol, which gives me joint pain.

I have been pondering this question today Turnbuckle. It sounds possible but would the survival of the Baati rats make your speculation not probable? Mainly, what would prevent them from suffering the malady of stem cell depletion?

From what I can tell adult stem cells suffer the same types of calamities as do ordinary cells. Mainly, they gather damaged or abnormal intracellular molecules through generations of division and they likely experience the degrading of mitochondria with replicative aging. What would be the effect on the rats should differentiation deplete the undifferentiated stem cells? Would it not result in the death of tissue cells since they would no longer be able to be repleted by stem cells?

It is reported that by the age of 50 we lose about 50% of our adult stem cells and 90% by age 65. It seems to me it is more likely stem cells are experiencing the same kinds of benefits as do other cells with c60. c60 is likely caring away unwanted intruders and possibly regenerating mitochondria and or preventing ROS. As we age we heal more slowly because we have a reduction of stem cells. Is this also the same reason we age? We age mainly because we can not regenerate cells. It does not seem logical to me that stem cells would suddenly start to just differentiate and produce no children. It is likely we have a limited set and they just degrade over time yet the new science points in a different direction. So, it is just as likely that c60 is stimulating a proliferation of new healthy stem cells that are differentiating thus resulting in faster healing.

On any account, I admit my ignorance yet felt the need to chime in (If not for the pure purpose of needing clarification).

Thanks...

Edited by solarfingers, 02 June 2013 - 05:47 AM.

[Turnbuckle]

With regard to the possibility that C60 is promoting stem cell differentiation--from reports of the disappearance of scars, the regrowth of hair, and the apparent re-stimulation of a knee injection of stem cells--there isn't any obvious reason why C60 would also promote stem cell proliferation. And you need both proliferation and differentiation otherwise you could deplete them. So my protocol is now a single dose of C60 a week, and during the off days, several doses of supplements that promote proliferation. These are fucoidan, l-theanine, and blue-green algae, along with the astragalus I was already taking.

There are stem cell stimulating supplements on the market that contain these ingredients and others, but I am avoiding them because they contain resveratrol, which gives me joint pain.

I have been pondering this question today Turnbuckle. It sounds possible but would the survival of the Baati rats make your speculation not probable? Mainly, what would prevent them from suffering the malady of stem cell depletion?

From what I can tell adult stem cells suffer the same types of calamities as do ordinary cells. Mainly, they gather damaged or abnormal intracellular molecules through generations of division and they likely experience the degrading of mitochondria with replicative aging. What would be the effect on the rats should differentiation deplete the undifferentiated stem cells? Would it not result in the death of tissue cells since they would no longer be able to be repleted by stem cells?

It is reported that by the age of 50 we lose about 50% of our adult stem cells and 90% by age 65. It seems to me it is more likely stem cells are experiencing the same kinds of benefits as do other cells with c60. c60 is likely caring away unwanted intruders and possibly regenerating mitochondria and or preventing ROS. As we age we heal more slowly because we have a reduction of stem cells. Is this also the same reason we age? We age mainly because we can not regenerate cells. It does not seem logical to me that stem cells would suddenly start to just differentiate and produce no children. It is likely we have a limited set and they just degrade over time yet the new science points in a different direction. So, it is just as likely that c60 is stimulating a proliferation of new healthy stem cells that are differentiating thus resulting in faster healing.

On any account, I admit my ignorance yet felt the need to chime in (If not for the pure purpose of needing clarification).

Thanks...

Stems cells are like cancer cells, their mitochondria are shut down and they rely on glycolysis rather than oxidative processes for energy. Radicals are not a problem for them since they are not producing many. (That's not to say they don't pick up mtDNA errors anyway, but that is another story, having to do, most likely, with the absence of mitophagy.) My main concern is the depletion of the population of stem cells, and if C60 is stimulating the differentiation of stem cells by turning on mitochondria, then a user might see significant positive effects initially, but later on these effects might fade and he might even age more rapidly. So a complete longevity protocol would need an additional supplement that increases the body's population of stems cells. The Baati rats don't prove anything in this regard, because they don't live long enough. And when you say "It does not seem logical to me that stem cells would suddenly start to just differentiate and produce no children," a stem cell with active mitochondria is no longer a stem cell. Stem cells can reproduce into stem cells, stem cells and somatic cells, or only somatic cells, so if a supplement only promotes the last possibility, the body's store of stem cells would be rapidly depleted.

Edited by Turnbuckle, 02 June 2013 - 11:28 AM.

[solarfingers]

Stems cells are like cancer cells, their mitochondria are shut down and they rely on glycolysis rather than oxidative processes for energy. Radicals are not a problem for them since they are not producing many. (That's not to say they don't pick up mtDNA errors anyway, but that is another story, having to do, most likely, with the absence of mitophagy.) My main concern is the depletion of the population of stem cells, and if C60 is stimulating the differentiation of stem cells by turning on mitochondria, then a user might see significant positive effects initially, but later on these effects might fade and he might even age more rapidly. So a complete longevity protocol would need an additional supplement that increases the body's population of stems cells. The Baati rats don't prove anything in this regard, because they don't live long enough. And when you say "It does not seem logical to me that stem cells would suddenly start to just differentiate and produce no children," a stem cell with active mitochondria is no longer a stem cell. Stem cells can reproduce into stem cells, stem cells and somatic cells, or only somatic cells, so if a supplement only promotes the last possibility, the body's store of stem cells would be rapidly depleted.

That is indeed very interesting. I'm not aware as to the level of free radicals but I am aware that stem cells are weakened over their lifetime of subsequent divisions because of them. My interest was in the way that stem cells were depleted and my assumptions concerning c60 were derived from this statement I found in this study (link follows).

"However, as serial transplantation experiments subject stem cells to excessive rounds of cell division, it remains to be determined whether replicative aging alone is sufficient to contribute to the decline of stem cell function in long-lived mammals during normal aging. Adult stem cells are also susceptible to the kinds of age-related changes, namely chronological aging, that occur in nondividing cells, such as neurons and cardiomyocytes. These changes include the accumulation of damaged macromolecules, such as proteins, lipids, and nucleic acids, some of which may, in fact, aggregate and form stable, long-lived complexes that are toxic to the cell."

It makes sense to me that c60 would attract these macromolecules (if not their aggregates) and hopefully perpetuating the stem cell. I do not understand the chemistry involved here.

I was also unaware of the role of the mitochondria in stem cells which was assumptive of me. I did a quick Google search to find more information on the subject and ran across this discovery (link follows). Firstly, it isn't because the mitochondria in stem cells is inactive that they do not make energy through ATP but rather the mitochondria is active yet serving a different role.

"Surprisingly, the UCLA researchers discovered that pluripotent stem cell mitochondria respire at roughly the same level as differentiated body cells — but they produce very little energy, thereby uncoupling the consumption of sugar and oxygen from energy generation. Rather than finding that mitochondria matured with cell differentiation, as was anticipated, the researchers uncovered a mechanism by which the stem cells switch from glucose fermentation to oxygen-dependent respiration to achieve full differentiation potential."

and "... the molecular complexes responsible for respiration in the mitochondria of pluripotent stem cells — known as the electron transport chain — were functional."

"... a protein called uncoupling protein 2 (UCP2) was highly expressed in the stem cells. He also found that UCP2 blocked respiration substrates derived from sugar from gaining access to the mitochondria, instead shunting them to the glycolytic and biosynthesis pathways located in the cytoplasm. This inhibited the stem cells' ability to respire as a method of generating energy."

This would lend me to believe that c60 can have nothing to do with turning on mitochondria in stem cells. I cannot see why c60 would have any affect upon the UCP2 protein to short circuit their normal functioning either. c60 does not seem to react with any form of protein that we know of. What affect on mitochondrial aging might c60 play if any? Would resetting mitochondrial age be of benefit to stem cells?

Manifestations and mechanisms of stem cell aging

Scientists uncover mechanism that regulates human pluripotent stem cell metabolism

[ClarkSims]

With regard to the possibility that C60 is promoting stem cell differentiation--from reports of the disappearance of scars, the regrowth of hair, and the apparent re-stimulation of a knee injection of stem cells--there isn't any obvious reason why C60 would also promote stem cell proliferation.

Well I should add myself to the list of people with scar reduction. I had keloid scaring on my chest from an infected pimple. It really bothered me when I was doing a lot of outdoor running, swimming and triathlons back in 2009. I even started putting scarex on it.

I regret that I didn't photograph it before I started taking C60. I totally forgot about it in the last few years, because I have been running around the country doing consulting.

But anyway, the scar is almost completely gone now.

I pulled up this article on wikipedia

http://en.wikipedia.org/wiki/Keloid
My scare was not nearly so large, but it would often itch. This article is the first time I read that other people had issues with itching keloid scars.

Wikipedia states:

Histologically, keloids are fibrotic tumors characterized by a collection of atypical fibroblasts with excessive deposition of extracellular matrixcomponents, especially collagen, fibronectin, elastin, and proteoglycans.

I am guessing the tumors must be correlated with oxidative stress, and the C60 OO, stops the vicious cycle of tumor by stopping the oxidative stressl

I have also cut out almost all of the methionine in my diet, and have been taking methelyne blue. I bet the fibratic tumors have been going through apoptosis because of lack of methionine.

Edited by ClarkSims, 02 June 2013 - 03:45 PM.

[Turnbuckle]

With regard to the possibility that C60 is promoting stem cell differentiation--from reports of the disappearance of scars, the regrowth of hair, and the apparent re-stimulation of a knee injection of stem cells--there isn't any obvious reason why C60 would also promote stem cell proliferation.

Exactly. If you promote differentiation without proliferation, then you're going to run out.

As for mitochondria promoting differentiation, there's this paper--

It is possible that in differentiating ESCs [Embryonic stem cells], as the cells lose their pluripotency, specific retrograde signals from the mitochondria to the nucleus is essential for the transcriptional triggering of the genes associated with early differentiation. Indeed, we found that disruption of mitochondrial function during ESC differentiation repressed transcriptional programs required for embryonic lineage differentiation, and in particular, HOX gene expression both in mouse and human ESCs.

Mitochondrial Function Controls Proliferation and Early Differentiation Potential of Embryonic Stem Cells

And this paper is interesting--

These observations strongly suggest the existence of an
interplay between mitochondrial biogenesis and stem cell
differentiation.


Mitochondrial involvement in stemness and stem cell differentiation

[solarfingers]

Exactly. If you promote differentiation without proliferation, then you're going to run out.

As for mitochondria promoting differentiation, there's this paper--

It is possible that in differentiating ESCs [Embryonic stem cells], as the cells lose their pluripotency, specific retrograde signals from the mitochondria to the nucleus is essential for the transcriptional triggering of the genes associated with early differentiation. Indeed, we found that disruption of mitochondrial function during ESC differentiation repressed transcriptional programs required for embryonic lineage differentiation, and in particular, HOX gene expression both in mouse and human ESCs.

Mitochondrial Function Controls Proliferation and Early Differentiation Potential of Embryonic Stem Cells

What I can't get is where do we get the idea that the stem cells are no longer proliferating when differentiated cells are created? When a stem cell divides it does one of two things. It creates two new stem cells or it creates a stem cell and a progenitor cell. Stem cells themselves don't just morph into differentiated cells. The only way to deplete stem cells is for it to divide into two progenitor cells. What mechanism are you suggesting that can account for this? I see nothing in the paper that suggests that the natural process is being hampered but in fact:

Our results clearly demonstrate that retarding mitochondrial activity have distinct effects in self-renewing ESCs and during early differentiation.

One has to hinder the mitochondrial's activity in order to create problems. If c60 were to hinder mitochondrial activity all bets are off. There is no hope for it to be beneficial to any kind of cell.

And this paper is interesting--

These observations strongly suggest the existence of an
interplay between mitochondrial biogenesis and stem cell
differentiation.


Mitochondrial involvement in stemness and stem cell differentiation

Yes of course the mitochondrial processes changes during stem cell differentiation. Isn't this the case in any cell division? The mitochondria in progenitor cells must have an intermediate step before becoming a fully actualized specialized cell. I have no problem with the idea that mitochondria can play a role in creating differentiated cells. They aren't just turned on all of a sudden. I just fail to see the logic that this process necessitates that stem cells behave differently than normal and divide themselves to death. Where is the science that suggests this part is true? I'm not trying to be argumentative. I just fail to see the link.

[Turnbuckle]

What I can't get is where do we get the idea that the stem cells are no longer proliferating when differentiated cells are created? When a stem cell divides it does one of two things. It creates two new stem cells or it creates a stem cell and a progenitor cell. Stem cells themselves don't just morph into differentiated cells. The only way to deplete stem cells is for it to divide into two progenitor cells. What mechanism are you suggesting that can account for this? I see nothing in the paper that suggests that the natural process is being hampered but in fact:

Stem cells can also divide symmetrically into two differentiated cells, and this is the hypothetical concern I have, if C60 is indeed turning on mitochondria and kick-starting differentiation. If it is a misplaced concern and differentiation proceeds asymmetrically, I will be happy. The turning on of mitochondria is itself an hypothesis based on the observation of better oxygen utilization and the theoretical work indicating that C60 is attracted to the groove between DNA strands where it could presumably interfere with methytransferase and thereby turn on genes of mtDNA that had been incorrectly turned off. Procaine is another molecule believed to be a methyltransferase inhibitor (PMID 12941824), binds to the DNA groove, and extends the lifespan of Wistar rats.

Edited by Turnbuckle, 02 June 2013 - 07:00 PM.

[solarfingers]

Turbuckle, you certainly have given me more to chew on. Thank you for the stimulating dialogue.

[niner]

"Surprisingly, the UCLA researchers discovered that pluripotent stem cell mitochondria respire at roughly the same level as differentiated body cells — but they produce very little energy, thereby uncoupling the consumption of sugar and oxygen from energy generation. Rather than finding that mitochondria matured with cell differentiation, as was anticipated, the researchers uncovered a mechanism by which the stem cells switch from glucose fermentation to oxygen-dependent respiration to achieve full differentiation potential."

and "... the molecular complexes responsible for respiration in the mitochondria of pluripotent stem cells — known as the electron transport chain — were functional."

"... a protein called uncoupling protein 2 (UCP2) was highly expressed in the stem cells. He also found that UCP2 blocked respiration substrates derived from sugar from gaining access to the mitochondria, instead shunting them to the glycolytic and biosynthesis pathways located in the cytoplasm. This inhibited the stem cells' ability to respire as a method of generating energy."

This would lend me to believe that c60 can have nothing to do with turning on mitochondria in stem cells. I cannot see why c60 would have any affect upon the UCP2 protein to short circuit their normal functioning either. c60 does not seem to react with any form of protein that we know of. What affect on mitochondrial aging might c60 play if any? Would resetting mitochondrial age be of benefit to stem cells?

I think this is an important point. We are wondering if c60 induces differentiation, and the mechanism that seems to make sense is one that enhances OxPhos; essentially making mitochondria more efficient. The paper being discussed in this news release (available here, including free full text) suggests that stem cells already have competent mitochondria, and that they are just being deprived of fuel through the action of UCP2, if I understand correctly. When UCP2 expression is dialed down, then the mitochondria are off to the races, at least in theory, if Teitell and coworkers are right. If this is the mechanism whereby stemness is maintained, then I don't see how c60-oo is going to break that. On the other hand, maybe the mitochondria in stem cells aren't always as fully competent as Teitell and coworkers suggest. If that were the case, it might be possible for a stem cell to attempt a differentiation, but get stuck somewhere along the line because its mitochondria were not fully functional. This would be the state that I hypothesize could be "rescued" by c60-oo.

Regarding interactions between c60 and proteins, there are some known interactions between pristine c60 and, for example, the HIV protease. There are undoubtedly other cases where proteins contain a large hydrophobic site to which pristine c60 could bind. A multiply substituted c60, on the other hand, seems less likely to find a matching site on a protein. This is not to say it couldn't happen, but it seems unlikely to me.

I think that c60-oo plays a large role in mitochondrial aging by reducing the ROS level. That results in less damage to mtDNA which means fewer mitochondria that fail in a way that circumvents mitophagy and causes the cell to go senescent. It doesn't sound like mitochondria accrue a significant amount of damage in stem cells, so I'm not sure resetting their age would help much there. However, I don't think that we have a way to reset the age of mitochondria anyway. If we did, it would be a lot more useful in differentiated somatic cells.

[solarfingers]

Niner, I was kind of thinking the same thing but I doubt I could express it as well as you did. I also like the comment you made in a previous post on page 3 of this thread:

"I don't know. In the quoted passage, they say that mitochondria may also regulate the self-renewal of stem cells. Maintaining the appropriate balance between replication and differentiation is under the control of multiple pathways, one of which is the mitochondria and associated metabotype. We have multiple observations that could be explained by stem cell differentiation, and a switch to OXPHOS is part of that. I don't know if we're seeing the rescue of failed or "stuck" differentiations, or if we're seeing an encouragement of differentiation that wouldn't otherwise have happened. If the latter, I don't think we have any way of knowing, at this point, whether it's too much differentiation or not, or if C60 might even be resulting in more replication, either directly or as a consequence of increased differentiation. I'd sure like to find some stem cell guys and get them to run a few experiments."

My gut feeling is that c60 is protecting the mitochondria and internal processes from being disturbed by unregulated ROS as well as any rogue molecular junk that has been passed along through subsequent divisions. From what I'm reading, I cannot see how methyltransferase suppression or release can stimulate stem cell mitochondria if say c60 did find home in the grooves of stem cell DNA. First, none of the tests attempted to affect the mitochondria this way and secondly, the mitochondria in stem cells does not function the same way as they do in specialized cells. I do find it intriguing the role of ATP in the process of proliferation. If anything I would think that the release of methyltransferase would only serve as fuel for stem cells. Of course I leave the standard disclosure, I am no expert. A molecular biochemist will likely dance a dirge all over my thinking.

[Turnbuckle]

"Surprisingly, the UCLA researchers discovered that pluripotent stem cell mitochondria respire at roughly the same level as differentiated body cells — but they produce very little energy, thereby uncoupling the consumption of sugar and oxygen from energy generation. Rather than finding that mitochondria matured with cell differentiation, as was anticipated, the researchers uncovered a mechanism by which the stem cells switch from glucose fermentation to oxygen-dependent respiration to achieve full differentiation potential."

and "... the molecular complexes responsible for respiration in the mitochondria of pluripotent stem cells — known as the electron transport chain — were functional."

"... a protein called uncoupling protein 2 (UCP2) was highly expressed in the stem cells. He also found that UCP2 blocked respiration substrates derived from sugar from gaining access to the mitochondria, instead shunting them to the glycolytic and biosynthesis pathways located in the cytoplasm. This inhibited the stem cells' ability to respire as a method of generating energy."

This would lend me to believe that c60 can have nothing to do with turning on mitochondria in stem cells. I cannot see why c60 would have any affect upon the UCP2 protein to short circuit their normal functioning either. c60 does not seem to react with any form of protein that we know of. What affect on mitochondrial aging might c60 play if any? Would resetting mitochondrial age be of benefit to stem cells?

I think this is an important point. We are wondering if c60 induces differentiation, and the mechanism that seems to make sense is one that enhances OxPhos; essentially making mitochondria more efficient. The paper being discussed in this news release (available here, including free full text) suggests that stem cells already have competent mitochondria, and that they are just being deprived of fuel through the action of UCP2, if I understand correctly. When UCP2 expression is dialed down, then the mitochondria are off to the races, at least in theory, if Teitell and coworkers are right. If this is the mechanism whereby stemness is maintained, then I don't see how c60-oo is going to break that. On the other hand, maybe the mitochondria in stem cells aren't always as fully competent as Teitell and coworkers suggest. If that were the case, it might be possible for a stem cell to attempt a differentiation, but get stuck somewhere along the line because its mitochondria were not fully functional. This would be the state that I hypothesize could be "rescued" by c60-oo.

Regarding interactions between c60 and proteins, there are some known interactions between pristine c60 and, for example, the HIV protease. There are undoubtedly other cases where proteins contain a large hydrophobic site to which pristine c60 could bind. A multiply substituted c60, on the other hand, seems less likely to find a matching site on a protein. This is not to say it couldn't happen, but it seems unlikely to me.

I think that c60-oo plays a large role in mitochondrial aging by reducing the ROS level. That results in less damage to mtDNA which means fewer mitochondria that fail in a way that circumvents mitophagy and causes the cell to go senescent. It doesn't sound like mitochondria accrue a significant amount of damage in stem cells, so I'm not sure resetting their age would help much there. However, I don't think that we have a way to reset the age of mitochondria anyway. If we did, it would be a lot more useful in differentiated somatic cells.

The UCP connection is very interesting. C60 cannot effect the UCP genes directly as they are in the nuclear DNA, however if it did inhibit UCP, that would explain the very fast oxygen utilization response in some people and the apparent stimulation of stem cells. And you would expect a UCP inhibitor (genipin) to show similar effects--

Aim:
Heart ischaemia is well-known damaging agent, which is more evidently performed via mitochondria. Uncoupling proteins (namely UCP2 and UCP3) are the members of inner membrane transporters family that dissipating the proton gradient. Ischaemic injury and UCPs appear to be interrelated. In this study we hypothesized that UCPs are involved in pathological processes occurred in cardiac cells during ischaemia.

Methods:
In experiments on isolated rat hearts perfused under Langendorff preparation effects of ischaemia-reperfusion and blockade of UCPs with its inhibitor genipin (50 mg/L) was studied and cardiodynamic parameters were measured. Expression of UCPs was detected by reverse transcriptional polymerase chain reaction.

Results:
It was shown that postischaemic disturbances of cardiac contractility, coronary vessels tone and heart rate are accompanied with noneffective oxygen utilization by myocardial tissue. At the same time ischaemia (20 min) as well as subsequent reperfusion (40 min) increased expression of UCPs in myocardium: mRNA levels of UCP3 were significantly higher that those of UCP2, but both higher that in control. Blockade of UCPs by genipin has, in general, positive effect: increased indexes of cardiac contractility decreased oxygen cost of myocardial work and improved non-effective oxygen utilization by the heart tissue during perfusion. However, postischaemic heart disturbances after genipin administration were higher than in control.

http://www.blackwell...ID=737&id=61147

But if UCP is not a bad thing in the long run, taking an inhibitor continuously might be counterproductive--

There is evidence to suggest that higher levels of uncoupling
are beneficial when it comes to aging. Outbred MF1 mice with
high metabolic rates live longer and have higher rates of
mitochondrial proton conductance, a difference mediated, at
least in part, by UCP3. Swiss Webster mice treated with
low doses of the uncoupling agent 3,4-dinitrophenol showed
increased mean lifespan and metabolic changes similar to those
seen in caloric restriction, the only intervention that reliably
increases lifespan.

Coupled with uncouplers: the curious case of lifespan

Edited by Turnbuckle, 03 June 2013 - 11:45 AM.

[solarfingers]

Turnbuckle,

How does taking intermittent dosages prevent c60 from causing stem cells from differentiating themselves out of existence? I'm not completely sold on the idea but that doesn't mean that I should throw all caution out into the wind. Niner is taking intermittent dosages as well yet for different reasons. You are both very astute in this area and I would be amiss not to take your thoughts and methodology into account.

[Turnbuckle]

Turnbuckle,

How does taking intermittent dosages prevent c60 from causing stem cells from differentiating themselves out of existence? I'm not completely sold on the idea but that doesn't mean that I should throw all caution out into the wind. Niner is taking intermittent dosages as well yet for different reasons. You are both very astute in this area and I would be amiss not to take your thoughts and methodology into account.

I'm taking it intermittently because I get better results that way and because the Baati study was intermittent. Also, my theory that C60 might be epigenetically modifying the DNA of mitochondria suggests that allowing time for the better mitochondria to replicate and the defective ones to be removed by mitophagy would evolve the stochastically altered cellular population to a higher level of functioning.

[solarfingers]

I'm taking it intermittently because I get better results that way and because the Baati study was intermittent. Also, my theory that C60 might be epigenetically modifying the DNA of mitochondria suggests that allowing time for the better mitochondria to replicate and the defective ones to be removed by mitophagy would evolve the stochastically altered cellular population to a higher level of functioning.

Sounds reasonable... I like the idea of removing defective mitochondria. On any course I think I will follow suite with both you and Niner and take intermittent doses. It never hurts to be cautious.

Thank you...

[randomname]

I'm taking it intermittently because I get better results that way and because the Baati study was intermittent. Also, my theory that C60 might be epigenetically modifying the DNA of mitochondria suggests that allowing time for the better mitochondria to replicate and the defective ones to be removed by mitophagy would evolve the stochastically altered cellular population to a higher level of functioning.

Sounds reasonable... I like the idea of removing defective mitochondria. On any course I think I will follow suite with both you and Niner and take intermittent doses. It never hurts to be cautious.

Thank you...

is turnbuckle still on one dose a week?

[Turnbuckle]

Another paper has recently been posted on pubmed re [hydroxylated] C60 and NAC--

The effects of N-acetyl-L-cysteine (NAC) on cytotoxicity caused by a hydroxylated fullerene [C60(OH)24], which is known a nanomaterial and/or a water-soluble fullerene derivative, were studied in freshly isolated rat hepatocytes. The exposure of hepatocytes to C60(OH)24 at a concentration of 0.1 mM caused time (0-3 h)-dependent cell death accompanied by the formation of cell blebs, loss of cellular ATP, and reduced glutathione (GSH) and protein thiol levels, as well as the accumulation of glutathione disulfide and malondialdehyde (MDA), indicating lipid peroxidation. Despite this, C60(OH)24-induced cytotoxicity was effectively prevented by NAC pretreatment ranging in concentrations from 1 to 5 mM. Further, the loss of mitochondrial membrane potential (MMP) and generation of oxygen radical species in hepatocytes incubated with C60(OH)24 were inhibited by pretreatment with NAC, which caused increases in cellular and/or mitochondrial levels of GSH, accompanied by increased levels of cysteine via enzymatic deacetylation of NAC. On the other hand, severe depletion of cellular GSH levels caused by diethyl maleate at a concentration of 1.25 mM led to the enhancement of C60(OH)24-induced cell death accompanied by a rapid loss of ATP. Taken collectively, these results indicate that pretreatment with NAC ameliorates (a) mitochondrial dysfunction linked to the depletion of ATP, MMP, and mitochondrial GSH level and (b) induction of oxidative stress assessed by reactive oxygen species generation, losses of intracellular GSH and protein thiol levels, and MDA formation caused by C60(OH)24, suggesting that the onset of toxic effects is at least partially attributable to a thiol redox-state imbalance as well as mitochondrial dysfunction related to oxidative phosphorylation.

http://www.ncbi.nlm....pubmed/23877122

I think this finding can probably be generalized to C60 in EVOO.

[niner]

I think this finding can probably be generalized to C60 in EVOO.

I don't really see it... This was run at 0.1 millimolar concentration, while a milligram of c60 is only 1.4 micromoles. This experiment appears to have been run in vitro, presumably with atmospheric O2 concentration, and possibly with UV exposure. They're observing oxidative stress, while we observe antioxidant effects. It seems to be the opposite of c60 in EVOO, if anything. Or were you referring to the idea of NAC being beneficial? After trying both NAC and acetyl glutathione with c60, I can't say that I noticed anything.

[Turnbuckle]

I think this finding can probably be generalized to C60 in EVOO.

I don't really see it... This was run at 0.1 millimolar concentration, while a milligram of c60 is only 1.4 micromoles. This experiment appears to have been run in vitro, presumably with atmospheric O2 concentration, and possibly with UV exposure. They're observing oxidative stress, while we observe antioxidant effects. It seems to be the opposite of c60 in EVOO, if anything. Or were you referring to the idea of NAC being beneficial? After trying both NAC and acetyl glutathione with c60, I can't say that I noticed anything.

If one mg of C60 is 1.4 micromoles, then 70 mg is 0.1 millimoles, so it's not that far off the doses some are taking. But you are right, I'm bringing this up because of the previous discussion of NAC as being helpful when taking C60, with my idea that C60-enhanced mitochondrial activity uses up glutathione more rapidly. NAC should be helpful, and also L-glutathione reduced.

[niner]

If one mg of C60 is 1.4 micromoles, then 70 mg is 0.1 millimoles, so it's not that far off the doses some are taking.

Well, that would be the case if the person's effective volume were one liter, since 0.1 mM is 0.1 millimole per liter. The "effective volume" of a person varies according to the chemical characteristics of the drug. In the pharmacokinetic literature, it would be called the Volume of Distribution. Highly lipophilic drugs tend to have a very large volume of distribution- even as high as thousands of liters. I don't know exactly what it would be for a c60 fatty acid adduct, but it would probably be pretty large.

[bew4lsh]

Hey guys, new to the forum, and medically uneducated but I study systems in general. With regard to the reports that people experience a 'dropping off' of the effects with prolonged daily administration, have you all considered the possibility that you're just bottlenecked at a different performance gap after a certain number of days treating?

Note that I'm a year in on my c60oo dosage, daily ~2.4mg and have never experienced any gaps or decline in effectiveness. I strength train every day, and I also take athletic greens 2x a day. I recently added PQQ to my supplements list and noticed an additional and immediate improvement in endurance, above and beyond what I originally experienced. I took 7 minutes off of my previous week's 5k time, with no prior speed training, on a random day. I only experience lethargy and maybe a little general anxiety or lessened ability to handle job related stress when I stop taking the c60oo.

I did also notice on the day I began taking PQQ a small freckle develop on my right iris. Here's hoping it's not a little baby tumor caused by photoexcitation of the c60. Tomorrow's price!

[Hebbeh]

I recently added PQQ to my supplements list and noticed an additional and immediate improvement in endurance, above and beyond what I originally experienced. I took 7 minutes off of my previous week's 5k time, with no prior speed training, on a random day

7 minutes off your 5k time virtually overnite with no increased training is huge...in the neighborhood of a 30% improvement for the average recreational trail pounder. What were your before and after times?

[RJ23_1989]

That's beyond huge, and works out to over 2min/mile of pace improvement. Doable at say 12 to 10min/mile but beyond that..?


Too bad PQQ did zilch for me and I specifically took it to improve running performance.

BTW, 7min of 5k race time can literally be the difference between a local top 30 finisher (20min) and elite national level (13min).

Sent from my SCH-I605 using Tapatalk 2



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[bew4lsh]

Oh no I hate to be a huge disappointment but my previous best was 34:36 and I was able to get it in 27:15 on tuesday, that is by far the hardest I've ever run but it felt really good, powerful runner's high at the end I think. I wanted to eat tigers. I grew up asthmatic and as such never got to build much of an aerobic base. Bear in mind this is on a treadmill in the air conditioning. I noticed that my heartrate got up above 180, but felt comfortable, whereas normally that would be an indicator that I'm out of breath. 27 years old, 205 lbs, muscular build but with somewhere between 15-18% body fat. My squat strength has also increased, 4 weeks ago I was able to push 275 6 times, on tuesday (before my run!) I got 275 for 12 reps. I don't keep a training log, but I rarely train squats or leg press for gains since I already have tree trunk legs. I personally believe my knee cartilage is over sized compared to a year ago as well. If anybody wants to supply me with some type of test training schedule I'd be happy to keep to it as long as It's not less intense than I'm used to. 5 days a week strength training, accompanied by alternating daily 1 or 3 mile runs. I work from home so I usually have lots of time for recovery.

I stated elsewhere but I'd like to drop it here too: I think c60oo's efficacy is based in its surface area, the number of electrons it can accept, structural resilience, accessible electron affinity/ionization energy, and redox recombination. All those factors together make it versatile in that it can hand off radicals to enzymes, or combine two to form a stable molecule, repeatedly and continuously. Your average vitamins C/E are only able to donate two electrons before requiring recycling, right? You're getting a different level of efficiency out of c60 than you could from other molecules. Would that mean other pieces of the system get worked harder than they're prepared to compensate for? Can we as a group discuss and consider those possibilities?

A friend of mine works for the Moffit cancer research center, she says I should stop taking this stuff as she thinks it's probably somehow killing me. I'm going for blood work on the 6th, in the mean time what do you guys think?

[RJ23_1989]

ahhh..ok! That makes sense Congrats on such a huge jump in progress. 27 is certainly a respectable time and can be a good starting point to start making some decent incremental gains. How I wish the days of easy gains were still there for me, I'd gladly take even 1 min off and jump for joy if that happened. No such luck for me though!

Indirectly C60 has helped me - not specifically in aerobic endurance, but I've found that I recover about 1/3 (sometimes 50%) faster than I normally would and this has translated into better quality runs and some lower times. I can simply train harder and recover better. Recovery / Hormone mgmt. / Inflammation mgmt. are what I spend my time managing these days. I'll be 43 next month. It definitely doesn't get any easier the older you get

[niner]

I stated elsewhere but I'd like to drop it here too: I think c60oo's efficacy is based in its surface area, the number of electrons it can accept, structural resilience, accessible electron affinity/ionization energy, and redox recombination. All those factors together make it versatile in that it can hand off radicals to enzymes, or combine two to form a stable molecule, repeatedly and continuously. Your average vitamins C/E are only able to donate two electrons before requiring recycling, right? You're getting a different level of efficiency out of c60 than you could from other molecules. Would that mean other pieces of the system get worked harder than they're prepared to compensate for? Can we as a group discuss and consider those possibilities?

That's essentially how I see it. I'm convinced that c60-oo is a potent antioxidant, but it's very different from most molecules that we think of as "antioxidants". Its ability to easily accept (and stabilize) more than one electron is both unusual and important. Its catalytic activity distinguishes it from most other common antioxidants. The c60 fatty acid adduct is very hydrophobic, but with a polar head group. This makes it likely to be incorporated into a membrane, perhaps being converted to a phospholipid. Membrane localization, particularly in mitochondrial membranes, places it right where the action is, in terms of ROS production.

There are various ways that c60 might contribute to more efficient mitochondrial function. One way is through dismutation of superoxide, which should reduce the level of damage that superoxide causes to some of the enzymes in the Electron Transport Chain. Aconitase, in particular, is a target of superoxide. I haven't looked at this enough to know if aconitase function is in any way rate limiting, but there may be other enzymes similarly affected. Another possibility would make use of the ability of c60 to easily accept and donate electrons. Could it be occupying a space in the membrane between two ETC enzymes that allows it to pass an electron between them without requiring a diffusion / collision event? I don't know, but there's certainly a lot of biochemical bench work that could be done here to sort it all out.

A friend of mine works for the Moffit cancer research center, she says I should stop taking this stuff as she thinks it's probably somehow killing me. I'm going for blood work on the 6th, in the mean time what do you guys think?

Hmm. It certainly didn't hurt Baati's rats. They are very cancer-prone animals, but upon necropsy, none had any evidence of cancer. Rats certainly aren't humans, but they are mammals, which is a hell of a lot better than the usual cells, worms, or fruit flies that people get excited or terrified about. On the basis of what I know about the main c60-oo producers, I'd estimate that it's been in five to ten thousand humans by now. There haven't been any reliable reports of harm than I'm aware of. On the other hand, we're seeing a profusion of reports that suggest it is very good for people and other animals. You might ask your friend what she bases her belief on.

[free10]

With regard to the possibility that C60 is promoting stem cell differentiation--from reports of the disappearance of scars, the regrowth of hair, and the apparent re-stimulation of a knee injection of stem cells--there isn't any obvious reason why C60 would also promote stem cell proliferation. And you need both proliferation and differentiation otherwise you could deplete them. So my protocol is now a single dose of C60 a week, and during the off days, several doses of supplements that promote proliferation. These are fucoidan, l-theanine, and blue-green algae, along with the astragalus I was already taking.

There are stem cell stimulating supplements on the market that contain these ingredients and others, but I am avoiding them because they contain resveratrol, which gives me joint pain.

I have been pondering this question today Turnbuckle. It sounds possible but would the survival of the Baati rats make your speculation not probable? Mainly, what would prevent them from suffering the malady of stem cell depletion?

From what I can tell adult stem cells suffer the same types of calamities as do ordinary cells. Mainly, they gather damaged or abnormal intracellular molecules through generations of division and they likely experience the degrading of mitochondria with replicative aging. What would be the effect on the rats should differentiation deplete the undifferentiated stem cells? Would it not result in the death of tissue cells since they would no longer be able to be repleted by stem cells?

It is reported that by the age of 50 we lose about 50% of our adult stem cells and 90% by age 65. It seems to me it is more likely stem cells are experiencing the same kinds of benefits as do other cells with c60. c60 is likely caring away unwanted intruders and possibly regenerating mitochondria and or preventing ROS. As we age we heal more slowly because we have a reduction of stem cells. Is this also the same reason we age? We age mainly because we can not regenerate cells. It does not seem logical to me that stem cells would suddenly start to just differentiate and produce no children. It is likely we have a limited set and they just degrade over time yet the new science points in a different direction. So, it is just as likely that c60 is stimulating a proliferation of new healthy stem cells that are differentiating thus resulting in faster healing.

On any account, I admit my ignorance yet felt the need to chime in (If not for the pure purpose of needing clarification).

Thanks...

Stems cells are like cancer cells, their mitochondria are shut down and they rely on glycolysis rather than oxidative processes for energy. Radicals are not a problem for them since they are not producing many. (That's not to say they don't pick up mtDNA errors anyway, but that is another story, having to do, most likely, with the absence of mitophagy.) My main concern is the depletion of the population of stem cells, and if C60 is stimulating the differentiation of stem cells by turning on mitochondria, then a user might see significant positive effects initially, but later on these effects might fade and he might even age more rapidly. So a complete longevity protocol would need an additional supplement that increases the body's population of stems cells. The Baati rats don't prove anything in this regard, because they don't live long enough. And when you say "It does not seem logical to me that stem cells would suddenly start to just differentiate and produce no children," a stem cell with active mitochondria is no longer a stem cell. Stem cells can reproduce into stem cells, stem cells and somatic cells, or only somatic cells, so if a supplement only promotes the last possibility, the body's store of stem cells would be rapidly depleted.

I wouldn't say radicals/ros are not a problem for stem cells, if they exist where normal cells do. The body fills up with more and more senescent cells until we are dead, and those cells have major impacts on surrounding non senescent cells, as the senescent cells spew forth their poisons/radicals, and they can change normal cells into also being senescent cells. C60 may help with this.

[cuprous]

A friend of mine works for the Moffit cancer research center, she says I should stop taking this stuff as she thinks it's probably somehow killing me. I'm going for blood work on the 6th, in the mean time what do you guys think?

Watch the Baati interview (google it) on c60. One point he is emphatic about is that c60 is non-toxic. Could there be deliteruous effects from long-term usage? Possibly. But in the mean time the only negatives I'm reading about are just conjecture (e.g., c60 might cause your stem cell pool to differentiate quickly thereby cause you to have a big bounce in terms of health benefits followed by something worse). Is your friend at all knowledgeable about fullerene? Her comments sounds like offhand dismissal.

[mikey]

A friend of mine works for the Moffit cancer research center, she says I should stop taking this stuff as she thinks it's probably somehow killing me. I'm going for blood work on the 6th, in the mean time what do you guys think?

Watch the Baati interview (google it) on c60. One point he is emphatic about is that c60 is non-toxic. Could there be deliteruous effects from long-term usage? Possibly. But in the mean time the only negatives I'm reading about are just conjecture (e.g., c60 might cause your stem cell pool to differentiate quickly thereby cause you to have a big bounce in terms of health benefits followed by something worse). Is your friend at all knowledgeable about fullerene? Her comments sounds like offhand dismissal.

He also said that it was not toxic when taken long term later in the video.

Edited by mikey, 10 September 2013 - 06:05 AM.

[mait]

http://nextbigfuture...gave.html#more:

Researchers took a naturally occurring mitochondrial transcription factor called TFAM, which initiates protein synthesis, and engineered it to cross into cells from the bloodstream and target the mitochondria.

Aged mice given modified TFAM showed improvements in memory and exercise performance compared with untreated mice. "It was like an 80-year-old recovering the function of a 30-year-old," says Rafal Smigrodzki, also at Gencia, who presented the results at the Strategies for Engineered Negligible Senescence conference in Cambridge this month.

Targeted mitochondrial therapeutics in aging (SENS 6)

http://www.sens.org/...apeutics-aging:

Mitochondrial dysfunction in aging consists of relative suppression of oxidative phosphorylation and frequently an increase in glycolysis. This metabolic imbalance is triggered by progressive biochemical processes, including accumulation of mitochondrial mutations, and changes in the expression and function of nuclear-encoded mitochondrial proteins. Our group developed methods for mitigation of mitochondrial suppression through mitochondria-targeted therapeutics. We observed that stimulation of mitochondrial activity both in vitro and in vivo significantly improves cellular function, suppresses neoplastic growth and inflammation, improves aged animal cognition and resolves in vivo metabolic derangements. One of our therapeutics, an engineered mitochondrial transcription factor, prolonged survival in wild-type aged animals. We expect that mitochondrial stimulation will be an important part of future aging therapies.

[tintinet]

Oh no I hate to be a huge disappointment but my previous best was 34:36 and I was able to get it in 27:15 on tuesday, that is by far the hardest I've ever run but it felt really good, powerful runner's high at the end I think. I wanted to eat tigers. I grew up asthmatic and as such never got to build much of an aerobic base. Bear in mind this is on a treadmill in the air conditioning. I noticed that my heartrate got up above 180, but felt comfortable, whereas normally that would be an indicator that I'm out of breath. 27 years old, 205 lbs, muscular build but with somewhere between 15-18% body fat. My squat strength has also increased, 4 weeks ago I was able to push 275 6 times, on tuesday (before my run!) I got 275 for 12 reps. I don't keep a training log, but I rarely train squats or leg press for gains since I already have tree trunk legs. I personally believe my knee cartilage is over sized compared to a year ago as well. If anybody wants to supply me with some type of test training schedule I'd be happy to keep to it as long as It's not less intense than I'm used to. 5 days a week strength training, accompanied by alternating daily 1 or 3 mile runs. I work from home so I usually have lots of time for recovery.

I stated elsewhere but I'd like to drop it here too: I think c60oo's efficacy is based in its surface area, the number of electrons it can accept, structural resilience, accessible electron affinity/ionization energy, and redox recombination. All those factors together make it versatile in that it can hand off radicals to enzymes, or combine two to form a stable molecule, repeatedly and continuously. Your average vitamins C/E are only able to donate two electrons before requiring recycling, right? You're getting a different level of efficiency out of c60 than you could from other molecules. Would that mean other pieces of the system get worked harder than they're prepared to compensate for? Can we as a group discuss and consider those possibilities?

A friend of mine works for the Moffit cancer research center, she says I should stop taking this stuff as she thinks it's probably somehow killing me. I'm going for blood work on the 6th, in the mean time what do you guys think?

Blood work results, or did it kill you?

Edited by tintinet, 28 September 2013 - 10:59 PM.