635 replies to this topic

[Turnbuckle]

I'm reposting this moved post because it has merit re the scientific discussion on C60. If not, feel free to delete.

Here's an interesting paper which touches on the crosstalk between mitochondria and the nuclear epigenome--ie, if mitochondria aren’t healthy, this can result in hypermethylation of tumor suppressing genes in the nDNA, resulting in cancer.

While it is quite clear that the mitochondrial impairment
commonly seen in cancer cells leads to increased damage to the
nuclear genome and to changes in nuclear gene-expression, the
question of epigenetic changes related to mitochondrial dysfunction
has not been addressed. DNA methylation is an epigenetic
modification of the DNA that is frequently disrupted in nearly all
types of cancer. Hypomethylation of the repetitive elements associated
with increased genomic instability is frequently seen and
the hypermethylation of specific CpG islands in promoter regions
of several tumor-suppressor genes is commonly observed to be
associated with transcriptional silencing of the gene. To date,
it is unclear whether the mtDNA affects epigenetic changes in the
nuclear genome. In this study, we took a genomic-scanning approach
to identifying CpG island methylation changes associated with the
depletion and repletion of mtDNA. Our study suggests that mitochondrial
impairment induces DNA methylation in the nuclear
genome, and that some, but not all, of the changes induced by the
depletion of the mitochondrial genome can be reversed by reintroduction
of wild-type mitochondria.

Source: A novel role for mitochondria in regulating epigenetic modifications in the nucleus

Thus the epigenetic changes in nuclear DNA that promote cancer “can be reversed by reintroduction of wild-type mitochondria,” and it is logical to assume that they might also be reversed by restoring mitochondrial health, which C60 treatment seems to do.

While the thrust of the paper was cancer suppressor genes, it seems reasonable that other genes will be affected as well, and C60 could thus impact general health by indirectly altering the epigenetic status of nDNA.

Edited by Turnbuckle, 13 November 2012 - 11:30 AM.

[smithx]

There's nothing in that paper to imply that random changes in methylation would be beneficial.
I also am not aware of any data showing that C60/OO would have any effect on methylation.
And if C60/OO did affect methylation, the changes would be likely to be random.

Taken together, this means that it's extremely unlikely that C60/OO would be producing any beneficial changes in mitochondrial DNA due to methylation.

[niner]

Here's an interesting paper which touches on the crosstalk between mitochondria and the nuclear epigenome--ie, if mitochondria aren’t healthy, this can result in hypermethylation of tumor suppressing genes in the nDNA, resulting in cancer.

While it is quite clear that the mitochondrial impairment
commonly seen in cancer cells leads to increased damage to the
nuclear genome and to changes in nuclear gene-expression, the
question of epigenetic changes related to mitochondrial dysfunction
has not been addressed. DNA methylation is an epigenetic
modification of the DNA that is frequently disrupted in nearly all
types of cancer. Hypomethylation of the repetitive elements associated
with increased genomic instability is frequently seen and
the hypermethylation of specific CpG islands in promoter regions
of several tumor-suppressor genes is commonly observed to be
associated with transcriptional silencing of the gene. To date,
it is unclear whether the mtDNA affects epigenetic changes in the
nuclear genome. In this study, we took a genomic-scanning approach
to identifying CpG island methylation changes associated with the
depletion and repletion of mtDNA. Our study suggests that mitochondrial
impairment induces DNA methylation in the nuclear
genome, and that some, but not all, of the changes induced by the
depletion of the mitochondrial genome can be reversed by reintroduction
of wild-type mitochondria.

Source: A novel role for mitochondria in regulating epigenetic modifications in the nucleus

Thus the epigenetic changes in nuclear DNA that promote cancer “can be reversed by reintroduction of wild-type mitochondria,” and it is logical to assume that they might also be reversed by restoring mitochondrial health, which C60 treatment seems to do.

Nice paper. It shows how profoundly important it is to have healthy mtDNA. It provides a mechanistic explanation for the way that ROS, by damaging mtDNA, can indirectly lead to cancer, which could also be taken as an explanation for Baati's rats not having turmors at death.

[Andey]

What about possibility that concerns about lowering dosage and going to intermitent regimen based on fact that majority here taking too much of C60oo ?
Similar antioxidant Skulachevs SkQ1 have sweet spot on nmol per kg dosages as shown on this graph. I dont think that this is classic U shape graph because no sign of going worse than control.



Methylene Blue is also a mitochonrial antioxidant and it also have his sweet spot for this use (at least that was written in Wikipedia))

We all started with some approximation of Baati rat dosages.
Sellers of ready to use C60 products propose variants that majority of newcamers will stick to, and this dosage price is suprisingly around $30 for month supply...What a coincedence that this is sweet spot for supplements price. ))

May be somebody can propose an experiment or blood work to evaluate such dosage ? I think that medicine and pharma industries already have recipes to evaluate drug dosages, may be we could use their conventional experience ?

[Turnbuckle]

What about possibility that concerns about lowering dosage and going to intermitent regimen based on fact that majority here taking too much of C60oo ?
Similar antioxidant Skulachevs SkQ1 have sweet spot on nmol per kg dosages as shown on this graph. I dont think that this is classic U shape graph because no sign of going worse than control.



Methylene Blue is also a mitochonrial antioxidant and it also have his sweet spot for this use (at least that was written in Wikipedia))

We all started with some approximation of Baati rat dosages.
Sellers of ready to use C60 products propose variants that majority of newcamers will stick to, and this dosage price is suprisingly around $30 for month supply...What a coincedence that this is sweet spot for supplements price. ))

May be somebody can propose an experiment or blood work to evaluate such dosage ? I think that medicine and pharma industries already have recipes to evaluate drug dosages, may be we could use their conventional experience ?

When Skulachev redid this work with rats in a low-pathogen environment, he found that the longevity effect disappeared. http://www.ncbi.nlm....pubmed/22166671

Attached Files

•  SkQ1.jpg   36.7KB   29 downloads

[Andey]

What about possibility that concerns about lowering dosage and going to intermitent regimen based on fact that majority here taking too much of C60oo ?
Similar antioxidant Skulachevs SkQ1 have sweet spot on nmol per kg dosages as shown on this graph. I dont think that this is classic U shape graph because no sign of going worse than control.



Methylene Blue is also a mitochonrial antioxidant and it also have his sweet spot for this use (at least that was written in Wikipedia))

We all started with some approximation of Baati rat dosages.
Sellers of ready to use C60 products propose variants that majority of newcamers will stick to, and this dosage price is suprisingly around $30 for month supply...What a coincedence that this is sweet spot for supplements price. ))

May be somebody can propose an experiment or blood work to evaluate such dosage ? I think that medicine and pharma industries already have recipes to evaluate drug dosages, may be we could use their conventional experience ?

When Skulachev redid this work with rats in a low-pathogen environment, he found that the longevity effect disappeared. http://www.ncbi.nlm....pubmed/22166671

Didnt know that thanks ) It didnt prevent him to advertise herself as antiaging guru )
I found recently his project http://www.ussz.ru/ with ambitious name 'Earth without aging' ))

[YOLF]

Well there is a collection going on for the C60@home experiment with the rats. Why not take up another collection to do blood testing for humans that are just starting. Perhaps LEF would negotiate a good price for our tests? Considering some general biomarker tests could also be of use, insurance might cover some of it. One of my previous insurers gave me $600 a year for such things. Anyone got that kind of insurance and thinking about trying C60?

What about possibility that concerns about lowering dosage and going to intermitent regimen based on fact that majority here taking too much of C60oo ?
Similar antioxidant Skulachevs SkQ1 have sweet spot on nmol per kg dosages as shown on this graph. I dont think that this is classic U shape graph because no sign of going worse than control.



Methylene Blue is also a mitochonrial antioxidant and it also have his sweet spot for this use (at least that was written in Wikipedia))

We all started with some approximation of Baati rat dosages.
Sellers of ready to use C60 products propose variants that majority of newcamers will stick to, and this dosage price is suprisingly around $30 for month supply...What a coincedence that this is sweet spot for supplements price. ))

May be somebody can propose an experiment or blood work to evaluate such dosage ? I think that medicine and pharma industries already have recipes to evaluate drug dosages, may be we could use their conventional experience ?

[YOLF]

So LP extends life? Is LP the model for humans in developed nations? I suppose the usual conditions for rodents are zero pathogen? Sorry if this was already posted somewhere. Could it be that higher doses are required? What doses were used in the LP exps?

What about possibility that concerns about lowering dosage and going to intermitent regimen based on fact that majority here taking too much of C60oo ?
Similar antioxidant Skulachevs SkQ1 have sweet spot on nmol per kg dosages as shown on this graph. I dont think that this is classic U shape graph because no sign of going worse than control.



Methylene Blue is also a mitochonrial antioxidant and it also have his sweet spot for this use (at least that was written in Wikipedia))

We all started with some approximation of Baati rat dosages.
Sellers of ready to use C60 products propose variants that majority of newcamers will stick to, and this dosage price is suprisingly around $30 for month supply...What a coincedence that this is sweet spot for supplements price. ))

May be somebody can propose an experiment or blood work to evaluate such dosage ? I think that medicine and pharma industries already have recipes to evaluate drug dosages, may be we could use their conventional experience ?

When Skulachev redid this work with rats in a low-pathogen environment, he found that the longevity effect disappeared. http://www.ncbi.nlm....pubmed/22166671

Edited by cryonicsculture, 03 January 2013 - 09:31 PM.

[niner]

When Skulachev redid this work with rats in a low-pathogen environment, he found that the longevity effect disappeared. http://www.ncbi.nlm....pubmed/22166671

I wonder what's going on here? Could it be that the primary source of ROS-mediated damage in these animals, when exposed to the normal level of pathogens, is coming from the immune system in the form of pathogen-killing respiratory burst? A low pathogen environment is 'unusual', so I don't exactly know what to make of it. Since humans don't live in low pathogen environments, can we expect SkQ1 to work similarly for us? I think of SkQ1 as being like C60-oo, with better mitochondrial targeting, but a much worse antioxidant.

Alternate interpretation: Skulachev's controls in the first experiment were infected with some bug that killed a bunch of them, but the actives weren't infected. Or, the actives WERE infected, but SkQ1 had an antimicrobial effect. If the activity here is real, then one aspect that seems to be consistent about mitochondrially-directed or otherwise highly potent antioxidants is that they seem to be active at very low doses. Skulachev's 5 nM dose is a few micrograms.

[Turnbuckle]

Since humans don't live in low pathogen environments, can we expect SkQ1 to work similarly for us?

I think we do, at least relative to the past and relative to rats. We get vaccines and if we get sick enough, antibiotics.

[xEva]

When Skulachev redid this work with rats in a low-pathogen environment, he found that the longevity effect disappeared. http://www.ncbi.nlm....pubmed/22166671

I wonder what's going on here?

I think this is due to the fact that Skulachev's ion's action is similar in principle to an antimicrobial peptide (AMP), which is a positively charged ion with the affinity for the negatively charged bacterial membranes. AMPs act as natural antibiotics that disrupt the bacterial membranes. And of course, there is a similarity between mitochondrial and bacterial membranes. Administered PO, there is a greater chance for his ion to encounter a bacterium before it gets inside a cell to a mitochondrion.

I proposed long ago that this antibiotic action was responsible for the increased lifespan in the original experiment which had all indications of poor husbandry conditions.

Edited by xEva, 04 January 2013 - 04:18 AM.

[niner]

When Skulachev redid this work with rats in a low-pathogen environment, he found that the longevity effect disappeared. http://www.ncbi.nlm....pubmed/22166671

I wonder what's going on here?

I think this is due to the fact that Skulachev's ion's action is similar in principle to an antimicrobial peptide (AMP), which is a positively charged ion with the affinity for the negatively charged bacterial membranes. AMPs act as natural antibiotics that disrupt the bacterial membranes. And of course, there is a similarity between mitochondrial and bacterial membranes. Administered PO, there is a greater chance for his ion to encounter a bacterium before it gets inside a cell to a mitochondrion.

I proposed long ago that this antibiotic action was responsible for the increased lifespan in the original experiment which had all indications of poor husbandry conditions.

Could be. We'd need to explain the activity it shows at 5nM, which would be ~3mcg/liter. This is somewhat better than the best conventional antibiotics, looking at MIC50s. I found a couple antimicrobial peptide activities in the low micromolar range, which is not terrifically potent. Just looking at SkQ1, I don't see how it would disrupt a membrane, and if it did disrupt membranes, wouldn't it be a problem for mitochondrial membranes as well? This makes me think there is something else going on. It would at least be easy to measure an MIC for SkQ1, and maybe that's even been done already.

[xEva]

I think this is due to the fact that Skulachev's ion's action is similar in principle to an antimicrobial peptide (AMP), which is a positively charged ion with the affinity for the negatively charged bacterial membranes. AMPs act as natural antibiotics that disrupt the bacterial membranes. And of course, there is a similarity between mitochondrial and bacterial membranes. Administered PO, there is a greater chance for his ion to encounter a bacterium before it gets inside a cell to a mitochondrion.

I proposed long ago that this antibiotic action was responsible for the increased lifespan in the original experiment which had all indications of poor husbandry conditions.

Could be. We'd need to explain the activity it shows at 5nM, which would be ~3mcg/liter. This is somewhat better than the best conventional antibiotics, looking at MIC50s. I found a couple antimicrobial peptide activities in the low micromolar range, which is not terrifically potent. Just looking at SkQ1, I don't see how it would disrupt a membrane, and if it did disrupt membranes, wouldn't it be a problem for mitochondrial membranes as well? This makes me think there is something else going on. It would at least be easy to measure an MIC for SkQ1, and maybe that's even been done already.

That's interesting. First, 3mcg/L is it in water they drank or plasma concentrations they achieved?

Regardless, considering the number of bacteria in the body, most of which are concentrated in the large intestine (and those mice were not getting SkQ1 rectally), if we compare the number of bacteria to the number of mitochondria in the same body, I am afraid the number of mitochondria, for whom SkQ1 is intended is much larger. And yet you're saying that for this much larger population of mitochondria 5nM is enough, but for a smaller population of bacteria it does not quite make into MIC50 category -? Something does not compute here.

And yes, it is a well-known side effect of AMPs: they mess up host mitochondria (the fact I use in favor of stringent hygiene, a measure highly unpopular among young males lol). And so yes, AMPs carry heavy collateral damage (like most of the other measures of innate immunity). The damage is mediated by the fact that AMPs are mostly intended for the extracellular milieu even though they are produced inside the cell, and then... chaperoned for exocytosis -?

Finally, I thought that SkQ1 worked by making a hole in the membrane which lowered its tension. I also thought that less tension was good for mitochondria, but too little was deadly, for then no ATP could be produced. I also thought that bacteria care much more for the integrity of their membranes than host mitochondria. See, a bacterium in close vicinity to an eukaryote is subject to AMPs the eukaryote automatically produces upon encoutering a bacterial protein. If SkQ1 weakens bacterial membrane even slightly, it would have heavy repercussion for that bacterium.

Edited by xEva, 06 January 2013 - 04:00 PM.

[Turnbuckle]

If SkQ1 weakens bacterial membrane even slightly, it would have heavy repercussion for that bacterium.

No. That's not the way it works.

It should be stressed that SkQ1 possesses no antibiotic activity. Rather, it is favorable for survival of bacteria under conditions of oxidative stress (I. V. Manukhov et al., in preparation). Moreover, SkQ1 was without any effect on mortality of young mice infected by tuberculosis (A. S. Apt, personal communication). http://www.impactagi...ull/100404.html

Edited by Turnbuckle, 06 January 2013 - 04:36 PM.

[xEva]

If SkQ1 weakens bacterial membrane even slightly, it would have heavy repercussion for that bacterium.

No. That's not the way it works.

It should be stressed that SkQ1 possesses no antibiotic activity. Rather, it is favorable for survival of bacteria under conditions of oxidative stress (I. V. Manukhov et al., in preparation). Moreover, SkQ1 was without any effect on mortality of young mice infected by tuberculosis (A. S. Apt, personal communication). http://www.impactagi...ull/100404.html

Well, how does it work? According to Skulachev himself, SkQ1 is a funnel-shaped, positively-charged molecule which lodges into a negatively-charged membrane and stays there, lowering its tension.

Re your quote, it does not quite cut it. SkQ1 may not have much of an antibacterial action by itself, but as an adjunct to the natural workings of the innate immunity, it just might. Which is supported by a quote from the abstract of the paper you linked:

"The effect of SkQ1 on longevity of females is assumed to mainly be due to retardation of the age-linked decline of the immune system." That's the innate part of the immune sys that normally fails in old age.

As for this quote you bring up: "Moreover, SkQ1 was without any effect on mortality of young mice infected by tuberculosis ", mycobacteria which cause tuberculosis are intracellular bacteria, which eukaryotes don't bomb with AMPs but subject to xenophagy (a form of autophagy). There is a number of very potent antibiotics that are not effective against mycobacteria, which does not stop them from being antibiotics.

Sorry.

Edited by xEva, 06 January 2013 - 05:37 PM.

[Turnbuckle]

Re your quote, it does not quite cut it. SkQ1 may not have much of an antibacterial action by itself, but as an adjunct to the natural workings of the innate immunity, it just might. Which is supported by a quote from the abstract of the paper you linked:

"The effect of SkQ1 on longevity of females is assumed to mainly be due to retardation of the age-linked decline of the immune system." That's the innate part of the immune sys that normally fails in old age.

Not only does it not have "much of an antibacterial action," it actually protects bacteria. And that is in line with the common origins of bacteria and mitochondria. As for the comment about the immune system, that is an assumption by the researchers, but even if true, it doesn't translate to "an antibacterial action." Supplements that boost the immune system aren't considered antibacterial.

[xEva]

Well, I would be very weary taking anything 'actually protective of bacteria'. And I admit that SkQ1 is too small a molecule to qualify for a bona fide anti-microbial peptide (AMP).. ..but look what I found (based on similarity of SkQ1 with CoQ10):

http://www.ncbi.nlm.nih.gov/pubmed/21518260

... flies defective in CoQ biosynthetic gene coq2 were more susceptible to bacterial and fungal infections, while were more resistant to viruses. We found that Drosophila contained both CoQ9 and CoQ10, and food supplement of CoQ10 could partially rescue the impaired immune functions of coq2 mutants. ... We further showed that CoQ was essential for normal induction of anti-microbial peptides and amplification of viruses. ...

I also saw that CoQ10 is recommended everywhere for periodontal disease, which is a chronic infection.

So, yes, since SkQ1 and CoQ10 are similar, their antimicrobial action appears to be due to enhancement of innate immunity, namely induction of AMPs. So, I stand corrected (but not much, really). The net effect on bacteria is still the same which explains why SkQ1 extended lifespan in in badly cared for rats in the original experiment.

Edited by xEva, 08 January 2013 - 02:20 AM.

[motorcitykid]

Any speculation as to whether or not antioxidants could potentially negate the longevity effects of C60-oo?

I saw this article on tissue regeneration in tadpoles and thought "what if C60-oo worked through some latent genetic component in mammals involving ROS"?

[niner]

Any speculation as to whether or not antioxidants could potentially negate the longevity effects of C60-oo?

I saw this article on tissue regeneration in tadpoles and thought "what if C60-oo worked through some latent genetic component in mammals involving ROS"?

C60-oo IS an antioxidant. It is a hell of an antioxidant that blows the doors off of all previous antioxidants. I see no reason why taking a lesser antioxidant concurrently with c60-oo would negate its longevity effects.

The article on tadpole tale regeneration is just a reminder that radical-mediated signalling is alive and well. I think the fact that our biology uses radicals for purposes other than molecular mayhem is a pretty good reason to not go too crazy dosing c60 compounds. I use relatively low doses, taken intermittently. (Currently 15mg once a month).

[Turnbuckle]

C60-oo IS an antioxidant. It is a hell of an antioxidant that blows the doors off of all previous antioxidants.

Is there any empirical evidence for this?

[niner]

C60-oo IS an antioxidant. It is a hell of an antioxidant that blows the doors off of all previous antioxidants.

Is there any empirical evidence for this?

There's carboxyfullerenes acting as SOD mimetics. Then there's Buckminsterfullerenol free radical scavengers reduce excitotoxic and apoptotic death of cultured cortical neurons. The physical chemistry of C60 is well characterized. It accepts, holds, and donates electrons as needed. The reduction potentials are minimal up to a hexavalent anion, iirc.

Edited by niner, 15 January 2013 - 03:35 AM.

[Turnbuckle]

C60-oo IS an antioxidant. It is a hell of an antioxidant that blows the doors off of all previous antioxidants.

Is there any empirical evidence for this?

There's carboxyfullerenes acting as SOD mimetics. Then there's Buckminsterfullerenol free radical scavengers reduce excitotoxic and apoptotic death of cultured cortical neurons. The physical chemistry of C60 is well characterized. It accepts, holds, and donates electrons as needed. The reduction potentials are minimal up to a hexavalent anion, iirc.

Looking at the first citation, C60 with carboxylic groups was shown to be better than antioxidants E or PBN in protecting neurons from chemical insult, but that is a far cry from "blowing the doors off all previous antioxidants". They didn't compare it with really good antioxidants like BHT or BHA, for instance. One study did find that C60 was better than BHT when the right conjugates were used. Except that the conjugates used were BHT.

[niner]

You're failing to consider pharmacokinetics, tissue localization, and catalytic mode of action.

[Turnbuckle]

You're failing to consider pharmacokinetics, tissue localization, and catalytic mode of action.

I'm just looking for some empirical evidence to back up the marketing-like statements about its antioxidant value. I agree that it's good, but I doubt that it's anywhere as good as BHT.

[taho]

What if... C60-oo extends life not by reduction of ROS from mitochondria that damage the rest of the cell, but by protecting mitochondrial membrane from ROS and thus reducing rate of mitochondrial induced cell apoptosis?

[clairvoyant]

What if... C60-oo extends life not by reduction of ROS from mitochondria that damage the rest of the cell, but by protecting mitochondrial membrane from ROS and thus reducing rate of mitochondrial induced cell apoptosis?

Quite possible. Especially INNER mitochondrial membrane.

[smithx]

According to the research of Andrew Marks and his group at Columbia, age-related loss of muscle strength is due to leaky calcium channels. The calcium channel is made up of 4 proteins called the 'ryanodine receptor' which is so-named because a ryanodine attaches to it.




Dysfunctions with this receptor are also found in Duchenne muscular dystrophy, and Marks has said that, in effect, aging causes a form of muscular dystrophy.

http://www.skeletalm...m/content/2/1/9
http://www.pnas.org/...6/2198.abstract
https://www.cell.com...4131(11)00255-5

There are also similar structures in mitochondrial membranes.

http://www.jbc.org/c...6/24/21482.full

These leaky calcium channels not only cause muscle weakness, including problems like atrial fibrillation, but also cause damage to mitochondria and cause them to produce free radicals, further accelerating the damage.

http://www.nature.co...dis201031a.html

So, many causes of death may be attributable to oxidation of these intra-membrane calcium channels.

Since C60 is a powerful antioxidant, and we know that it gets into cell membranes, it is possible that it repairs and/or prevents damage to these calcium channels. This would explain some of the increased exercise abilities which some have noted, and would also provide one mechanism for C60 mediated life extension.

Edited by smithx, 29 June 2013 - 11:51 PM.

[smithx]

Here is a reference regarding the leaky calcium channels causing atrial fibrillation which is reversible when the functionality of the channels is restored (in this case by a small molecule called S107).

http://www.ncbi.nlm....pubmed/22828895

[hav]

That's a very interesting. Found a data sheet on S107 here. It indicates a method of operation on the calcium channel as via inhibiting S-nitrosylation of RyR1 thereby preventing the depletion of the protein calstabin-1:

A homotetramer of the ryanodine receptor (RyR1) forms a calcium channel that mediates skeletal muscle contraction. Calstabin-1 (FKBP12) associates with RyR1 and functions as a channel-stabilizing protein. Calstabin-1 loss or depletion following S-nitrosylation of RyR1 causes calcium leak and reduced muscle function. S107 is a benzothiazepine derivative that binds the RyR1 channel and enhances the binding affinity of calstabin-1. By preventing the depletion of calstabin-1 from the RyR1 complex, S107 slows muscle fatigue and reduces muscle damage in exercised mice. In a murine model of Duchenne muscular dystrophy, S107 reduces biochemical and histological evidence of the muscle damage associated with muscular dystrophy, improves muscle function, and increases exercise performance.

I noticed most of the studies indicate the same. Also interesting is that this study found that NAC has the same effect as S107 on another related protein, Calstabin-2, as well as on inhibiting RyR S-nitrosylation :

Leaky RyR2 trigger ventricular arrhythmias in Duchenne muscular dystrophy

We have previously reported that in vivo treatment with S107, an orally available, RyR-specific “rycal”, inhibited calstabin1 depletion from the RyR1 macromolecular complex in skeletal muscle In mdx hearts, treatment with the rycal S107 inhibited depletion of calstabin2 from the RyR2 complex without affecting the S-nitrosylation state of the channel (Fig. 1 A–C). Interestingly, treatment of the mice with N-acetyl cysteine (NAC) for 2 weeks also prevented RyR S-nitrosylation and calstabin2 depletion (Fig. S1), supporting the idea that S-nitrosylation of RyR2 occurs through the transformation of NO to peroxynitrite in the presence of superoxide anion (O2 .−).

Couldn't find any study observing c60 having a similar effect but I suspect it might be at least synergistic with S107 and NAC, perhaps by affecting superoxide anions.

Howard

[smithx]

Here's full text of the article "Ryanodine Receptor Oxidation Causes Intracellular Calcium Leak and Muscle Weakness in Aging"
http://www.ncbi.nlm....les/PMC3690519/

C60 might either get into the cell membrane and deoxidize the ryanodine receptors to some extent, repairing the calcium leakage, and/or they could get into the mitochondrial membrane and reduce superoxide, which would also decrease the oxidation of those receptors (and many other things).

Since the ryanodine receptors along with other proteins are likely to be recycled and replaced at some point, reduced superoxide would allow new receptors to keep working better for longer before they become oxidized.