3585 replies to this topic

[Turnbuckle]

This suggests that if C60 were to remove our DNA methylation, that would not be a good thing.

Methylation is definitely important in the nuclear DNA, but as C60 concentrates in the mitochondria, it's the mtDNA that will be affected.

[Allen Walters]

I wonder if the method of processing the c60 could effect the color in c60/oo? The first batch of c60 I received used solvent to process it, and the color was brown in the oo. The new stuff apparently had no solvents used in processing, and it has a deep ruby red color. Then again I used a very clear oo with the first batch.

[HighDesertWizard]

I've become convinced that, one way or another, to one degree or another, the effect in the Baati rats and some degree of the "Turnbuckle effects" will turn out to be TNF (Tumor Necrosis Factor) related. TNF has some relationship to very many Longevity and Health related genes. And for that reason, I think the probability of some TNF involvement in these observations is probable.

Because it's a distinct topic itself, I've established a thread about TNF here. I'm only about 1/2 through providing initial evidence demonstrating how important it is. Still, there are studies that show some impact on TNF by Fullerenes.

Modulation of tumor necrosis factor-mediated cell death by fullerenes

We've discussed the Mechanism of Action a great deal. At some point, perhaps we'll know enough to establish a hypothesis about an Object of Action, TNF.

Edited by wccaguy, 13 June 2012 - 12:09 PM.

[buckwheats]

This suggests that if C60 were to remove our DNA methylation, that would not be a good thing.

decreased chromosomal DNA methylation with age may be an evolved response to cellular damage, not a contributor to aging itself. one could imagine that decreased methylation -> increased protein synthesis could be a way the body helps pick up the slack from damaged cells.

of course removing methyl groups in a random way would probably not be good, even if removing specific ones would be.

Edited by buckwheats, 13 June 2012 - 10:00 PM.

[Metrodorus]

Lots of things could be going on in these rats, in multiple organ systems and biochemical systems, leading to overall lifespan extension.


For example, this 2012 study on functionalised fullerenes points (with the usual caveats) to a protective effect on neural tissue.

Based on the data that an aqueous molecule-colloidal solution of C₆₀ prevented amyloid-β_25-35 aggregation in in vitro experiments and based on our present evidence on the antitoxicity of an aqueous molecule-colloidal solution of C₆₀, we suggest that functionalised C₆₀prevents/diminishes amyloid-β_25-35 aggregation in vivo as well. Thus, an aqueous molecule-colloidal solution of C₆₀administered at a low concentration before amyloid-β_25-35, prevented disturbances in protein synthesis, neurodegeneration and formation amyloid-β_25-35 deposits in hippocampal pyramidal neurons in vivo. This evidence gives promise that functionalised C₆₀ can be used to develop anti-amyloid drugs combining antioxidant and anti-aggregative properties.
http://www.ingentaco...000001/art00011

[Metrodorus]

Interesting article on stated purity of fullerene samples supplied by manufacturers, and actual purity of the sample:

http://www.ipme.ru/e...0_gerasimov.pdf

When purchasing from a specific supplier, it might be worthwhile asking how the sample purity was assessed.

[zorba990]

Exposure to either UVA or visible light in the presence of >5 µM fullerol induced phototoxic damage. When cells were pretreated with non-toxic antioxidants: 20 µM lutein, 1 mM N-acetyl cysteine, or 1 mM L-ascorbic acid prior to irradiation, only the singlet oxygen quencher lutein significantly protected against fullerol photodamage. Apoptosis was observed in lens cells treated with fullerol whether or not the cells were irradiated, in the order UVA > visible light > dark. Dynamic light scattering (DLS) showed that in the presence of the endogenous lens protein α-crystallin, large aggregates of fullerol were reduced. In conclusion, fullerol is both cytotoxic and phototoxic to human lens epithelial cells. Although the acute toxicity of water soluble nano-C₆₀(OH)_22–26 is low, these compounds are retained in the body for long periods, raising concern for their chronic toxic effect. Before fullerols are used to deliver drugs to the eye, they should be tested for photo- and cytotoxicityin vivo.
http://www.ncbi.nlm....les/PMC2358981/

Maybe users of fullerene should all dress like Italians, and wear sunglasses?

Use of ascorbic acid and fullerenes protects against uvb, at least:
http://www.ncbi.nlm....pubmed/19800932

I use magnesium ascorbyl phosphate (MAP, water stable vitamin C analog) nearly everyday on my face as it with T-res seems a reasonable non toxic daily sunscreen without all that grease...

[Turnbuckle]

of course removing methyl groups in a random way would probably not be good, even if removing specific ones would be.

Even removing methyl groups randomly might not be bad as some will be improved even as others might be made worse. Each cell has a hundred to a thousand or more mitochondria, and each mitochondria reproduces on the order of days with an equal number subject to mitophagy. The cell has methods of selecting which mitochondria to recycle, and these (presumably) would be those that weren't performing up to snuff. Thus each cell has its own mitochondrial breeding factory where, hopefully, the best functioning organelles come to predominate. So if C60 works as a methyltransferase inhibitor, it would make sense to take long breaks between short treatments and to take supplements that support healthy mitophagy so that the population can shift to a higher level of functioning. It's possible that the researchers with their Wistar rats hit upon an effective dosing schedule by accident.

Edited by Turnbuckle, 14 June 2012 - 12:50 AM.

[Anthony_Loera]

The daily shot...

 uploadfromtaptalk1339637727221.jpg   94.12KB   18 downloads

Cheers
A

[HappyPhysicist]

Cheers!

[mpe]

Hey Anthony,
When will it be available?

[maxwatt]

The Carbon60 guy is already selling his version of it.. Premature, maybe, but I ordered 100 ml for my dog.

The dog is a 14-year old Wheaten Terrier. I've been administering resveratrol to her since she was eight, and it has held her arthritis at bay during that period. All her peers are long dead but one Lab, who also looks to be on his last legs. Even at 13, she was energetic and often mistaken for a puppy. No more. Last year I was traveling for several weeks, and she was looked after by others, and did not get her resveratrol. She has never been the same since, having visibly deteriorated when I returned. An infected cyst and treatment also did not help. Resumming resveratrol did not restore her. She is visibly an old dog, walks slowly, and has little enthusiasm outside a walk to the pet store for treats or the sight of a cat, which quickens her step.

Last night I was able to get her to eat 4 ml (.8mg/ml) of C60 by soaking it into a piece of bread. She stood up and walked in a circle for about a minute, then lay down and went back to sleep. This morning she seems more alert than usual, and has an unusually good appetite. I'll post any results or lack thereof. I kno the dose seems low, but I hope repeated treatment makes up for it. Getting a dog to drink olive oil is not easy.... maybe with a liver flavor?

One thing I'd like to see in further testing, is a comparison of low or no polyphenol olive oil with high polyphenol extra virgin olive oil. Remember the olive oil-alone group of rats also out-lived the controls, but not to as great a degree as the bucky-ball and olive oil group. Either C60 is a catalyst for EVOO polyphenols, or acts separately with an additive effect. It would be good to tease these apart.

[JohnD60]

Getting a dog to drink olive oil is not easy.... maybe with a liver flavor?

My dog likes the taste. But she pretty much eats anything. I just put it on top of her regular mourning meal and she eats it within a few minutes. She is in good health to begin with and only about eight years old, so it is unlikely I will have any dramatic improvement stories to tell. I am mainly wanting to see if it has any negative effect on her. I have been giving her 5ml/day, I will be increasing to 10ml/day soon. (.6mg/ml)

Edited by JohnD60, 14 June 2012 - 03:01 PM.

[Allen Walters]

Here it is today, I wouldn't have posted another pic, but it has turned a true blood red. It is clear, but so dark red that the light doesn't shine through very well.  IMG_20120614_140629.jpg   44.69KB   6 downloads

Edited by Allen Walters, 14 June 2012 - 06:35 PM.

[Spider_]

Allen, that is pretty much identical colour of my C60/OO. 8th day of dosing today at 10mg daily.

[Allen Walters]

Allen, that is pretty much identical colour of my C60/OO. 8th day of dosing today at 10mg daily.

Have you noticed any effects?

[Allen Walters]

I've noticed that I feel tired after a 2ml dose.

[Mind]

Sorry to beat a dead horse, but another cautionary post here, which could have also been posted in this thread.

[Spider_]

Have you noticed any effects?

Nothing whatsoever.

[maxwatt]

With regards to my dog, 14 is pretty damn old for a dog, near the maximum end of the curve for a dog her size and breed, but not a great outlier. She has had a pretty good run. If the C60 perks her up significantly, I might consider taking some.

C60 alone does seem to distribute itself in the middle of the cellular membrane of the mitochondria, based on in vitro tests (with illustrations) that was posted earlier in the C60 thread. Whether the EVOO polyphenoils go along for the ride or are irrelevant is an interesting question. But C60 is a potent antioxidant, so I suppose it is possible it is soaking up free radicals. Maybe.

Since the result of the study is so significant, one has to ask why wasn't it published in a prestigious journal like Science, instead of an obscure journal: the researchers had no funding for further tests? Science would have asked questions they could not answer without more testing for which they had no funds? They knew their work was shaky and wanted to publish anyway? They wanted to publish as quickly as possible to get more finding?

I hope it is reproducible, and applies to humans. I am encouraged toward experimentation in that toxicology studies seem to indicate pure C60 is apparently benign at worst. But I will still be pleasantly surprised if it turns out as beneficial as we hope. The more I learn, the less I know I know.

[smithx]

Even removing methyl groups randomly might not be bad as some will be improved even as others might be made worse.

I had a discussion with a bioresearcher friend of mine yesterday. He's an MD/PhD and has his own research lab at a local university where he's also a professor.

His was saying that one of the issues in aging is that genes which are harmful start getting expressed, and that this can be due to decreased methylation. The methylation was inhibiting expression of these harmful senescence genes, and when it goes, the genes become active, causing big problems with the cell. p16 is one of these genes, and he referred me to this article:
http://www.nature.co...ature10600.html

The point of the article is that when a 'bad gene' starts getting expressed, if the cell expressing the gene is destroyed (this study created a self-destruct mechanism for any cell which expressed the gene), the organism can live longer and be more healthy. This normally doesn't happen, and instead the tissue loses functionality and the organism becomes "aged".

This again points to the fact that randomly altering methylation patterns would not be a good thing.

Edited by smithx, 14 June 2012 - 08:25 PM.

[Turnbuckle]

I had a discussion with a bioresearcher friend of mine yesterday. He's an MD/PhD and has his own research lab at a local university where he's also a professor.

His was saying that one of the issues in aging is that genes which are harmful start getting expressed, and that this can be due to decreased methylation. The methylation was inhibiting expression of these harmful senescence genes, and when it goes, the genes become active, causing big problems with the cell. p16 is one of these genes, and he referred me to this article:
http://www.nature.co...ature10600.html

The point of the article is that when a 'bad gene' starts getting expressed, if the cell expressing the gene is destroyed (this study created a self-destruct mechanism for any cell which expressed the gene), the organism can live longer and be more healthy. This normally doesn't happen, and instead the tissue loses functionality and the organism becomes "aged".

This again points to the fact that randomly altering methylation patterns would not be a good thing.

Again, we're not talking nuclear DNA as it appears the C60 is concentrating in the mitochondria, which has only 37 genes. The mtDNA has a stripped down genome that doesn't have anything it doesn't need and everything it has is about running its energy factory. By contrast, the nuclear DNA needs its epigenome just to know what kind of cell it's supposed to support. Take that away and very bad things will happen so of course you don't want to demethylate it.

Edited by Turnbuckle, 14 June 2012 - 08:42 PM.

[smithx]

There is a distinct methylation pattern in mitochondrial DNA as well, and it changes in response to different stress conditions.

Biological systems are in a very delicate state of balance, and genes which are being inhibited by methylation are almost always being inhibited for a very specific reason.

It is certainly not true that all mitochondrial genes are being expressed to the same degree at all times, nor is it true that things would work well if that were the case.

Since again there is no evidence that C60 has anything to do with methylation, and since non-specifically altering methylation patterns would almost certainly be very detrimental, I would hope that this unfruitful speculation could be dropped once and for all.

[Turnbuckle]

There is a distinct methylation pattern in mitochondrial DNA as well, and it changes in response to different stress conditions.

Biological systems are in a very delicate state of balance, and genes which are being inhibited by methylation are almost always being inhibited for a very specific reason.

It is certainly not true that all mitochondrial genes are being expressed to the same degree at all times, nor is it true that things would work well if that were the case.

Since again there is no evidence that C60 has anything to do with methylation, and since non-specifically altering methylation patterns would almost certainly be very detrimental, I would hope that this unfruitful speculation could be dropped once and for all.

You hope this unfruitful speculation could be dropped once and for all? That's hilarious. Listen, smith, if you don't want to discuss it, that's fine, but other people just might.

[maxwatt]

If there is no way to test it, further speculation is meaningless, though it may be fun.

How would one confirm whether or not methylation of genetic material is occurring? And if it is, that it is responsible for the putative life extending effects seen?

[HighDesertWizard]

You hope this unfruitful speculation could be dropped once and for all? That's hilarious. Listen, smith, if you don't want to discuss it, that's fine, but other people just might.

Hey... Keep going Turnbuckle... I don't get it... Given the importance of this study, I think we ought to be helping each other find evidence for theories we find far fetched... It's Brain Storming Time...

But I'm not going to speculate in this note... I'm going to write out a few things I think we know for certain. Tell me what I've misunderstood about the facts...

• C60 inhibited TNF in one or more studies posted up thread. Can't recall the details.

• There are studies showing that TNF inhibition, by itself, can explain all the n=1 anecdotal observations we've heard about so far (including better sleep by the way). I posted about this up thread.

• TNF is demethylated during aging

• TNF has something to do with managing senescence

• TNF has something to do with p16

• management of TNF's harmful effects has profound implications for Extreme Longevity

• TNF is implicated in the kind of tumor growth that Cynthia Kenyon says are a key part of aging. (See the 2 recently posted videos of Cynthia Kenyon here at Longecity.)

I established that new TNF thread because I'm convinced there is overwhelming evidence it plays a more profound role in aging than we've realized. I'm not saying it's the only thing involved, just that it does play an important role. I'll present more evidence about the role of TNF soon in that thread...

Meanwhile, I'll try to get a handle on what kind of relationship C60 has had with TNF in previous studies...

Edited by wccaguy, 14 June 2012 - 11:59 PM.

[PWAIN]

How about breaking this thread into 2 or 3 separate threads? One could deal with speculation or mechanism of action, another with speculation on credibility of the work and another could deal with preparation of C60 oops solutions. This way the threads remain relevant and manageable.

[HighDesertWizard]

How about breaking this thread into 2 or 3 separate threads? One could deal with speculation or mechanism of action, another with speculation on credibility of the work and another could deal with preparation of C60 oops solutions. This way the threads remain relevant and manageable.

I agree. Not sure if 3 are needed. But certainly 2 would be better. It wouldn't take long to split the posts in thread into either one of two cateories. And there is still that third thread out there, what is longevity going to fi to further research about it.

[Mind]

Splitting the thread up is planned. Just will take some time for a mod to get around to it.

From the peanut gallery, so far, I am behind Niner's theory of enhanced membrane lipid functionality. It gets cut the least by occam's razor.

[HighDesertWizard]

From the peanut gallery, so far, I am behind Niner's theory of enhanced membrane lipid functionality. It gets cut the least by occam's razor.

In the second of two youtube videos she made last year, Cynthia Kenyon says that a key to Extreme Longevity is to keep from being overtaken by tumors... FOXO, P53, IGF1, among other genes, are key. Management of apoptosis and mitosis is critical, so says she, here...

http://www.youtube.com/watch?v=HxfLm30FHwA

I established that new thread about TNF to try to get a handle on these issues myself because I don't know much and I read too many abstracts with this sort of title...

Tumor necrosis factor-alpha mediates both apoptotic cell death and cell proliferation in a human hematopoietic cell line dependent on mitotic activity and receptor subtype expression

The truth is, I had to stop reading all the abstracts, I've resorted to browsing them, because there are way too many for me to read... Also, I found amazing literature associations between TNF and most of the key genes I have names for related to Longevity. I've documented those associations a bit in that thread.

Um, so... referencing Occam's Razor makes sense but that Razor isn't actual evidence and it's not "a good Explanation"...

When Cynthia Kenyon makes significant presentations about Longevity in C. Elegans--6 times normal life span--and she says Tumors are the important thing, I think we should pay attention.

And if we're going to pay attention to Human Tumors that means, among other things, looking very seriously at TNF, if only to dismiss it later to fall back to the Occam's Razor argument... The fact that the observed anecdotal effects of "the potion" can be explained, so far, with reference to TNF inhibition is important also...

Well, and there's this...

Calorie restriction inhibits the age-related dysregulation of the cytokines TNF-alpha and IL-6 in C3B10RF1 mice

TNF: A Cytokine triggered by the Immune System to Defend the Host that too often, with aging, continues the attack on healthy tissue, resulting in the Auto-Immune diseases that eventually kill most of us off.

Can I provide a complete Explanation of "the potion's" effects with reference to TNF right now? No, I can't. I'm hoping to coax folks smarter about these matters than I am into taking a more serious look and I'll keep pushing this button until they do...

Edited by wccaguy, 15 June 2012 - 07:45 AM.