635 replies to this topic

[treonsverdery]

 2000px-Buckminsterfullerene.svg.png   267.36KB   0 downloadsWhen I suggested that round legospherane nanodiamonds the same size as longevity fullerenes could be hydrogenated be like fullerenes I was actually thinking that fullerenes had hydrogens on them. (silly) there is a different possibility that is even niftier some reactions create = links from - links, putting legosperoid nanodiamonds through those reactions would give the partially saturated linkages of fullerenes at the nanodiamond surface.

Edited by treonsverdery, 02 May 2012 - 06:58 PM.

[HappyPhysicist]

I was thinking, we humans have been cooking our food for a long time and the soot from these fires maybe contained fullerenes. Perhaps fullerenes are an important part of the paleolithic diet.

[treonsverdery]

Its likely most readers here have read the imminst longecity idea that using spherical nanodiamonds the same diameter as fullerenes, then chemically modifying them to have a C-C=C-C=C surface is another approach to making a similar chemical to verify longevity effects with. Further, spermidine is published as doubling mouse lifespan at week 80. spermidine is an alkane NH2/\/\NH/\/NH2 thus ammonia on carbon molecules like NH2fullerenes may have even greater longevity effects. Perhaps the mice would live more than three times longer.

Kimberlite mineral could be used as a source of fullerene sized nanodiamond very cheaply

If any of the experimenters out there feel like grinding kimberlite, colloid density gradient separating to get nanodiamonds, then reacting to partially desaturate the nanodiamond surface, then seeing if it turns oil a different color, then feeding to rats you will be creating a natural products longevity drug that works along fullerene mechanisms

[revenant]

say what? Kimberlite is not a mineral, a rock yes..that's like saying pegmatite is a mineral..

[Metrodorus]

I came across this review article today, possibly the best overview on carbon 60 research viz risks to health that I have seen to date - although it does not take the most recent studies into account.

[Metrodorus]

There are almost no studies on lipofullerene - which is what we are dealing with here. Lipofullerene gives the solution its ruby red colour.

Some studies have been carried out on fullerene dissolved in squalane (extracted from olive oil), with no toxicity effects.

Fullerene dissolved in oil is no longer pristine fullerene, and the results from studies that deal with water based suspensions or other water-based solutions are almost irrelevant, as lipofullerene is to all intents and purposes a different molecule.

Edited by Metrodorus, 07 May 2012 - 11:54 AM.

[HappyPhysicist]

Metro,

Nice find on the Danish report. I see what you mean. The 'scary' reports of toxicity of C60 used tetrahydrofuran along with C60 and the Danish report basically says that these studies are irrelevant. I will still work on the filter apparatus but I will probably start taking C60 whether I get the filtering figured out or not.


"These interactions lead Stone et al. (2010) to the conclusions that ecotoxicological studies carried out with tetrahydrofuran do not have a high credibility. "

Edited by HappyPhysicist, 07 May 2012 - 12:14 PM.

[Metrodorus]

A couple more studies:
1. Bioavailability ( not of pristine carbon 60,but a derivative)
http://www.springerl...14/fulltext.pdf
2. Cardioprotective effects? Review study.

http://kopfinstrumen...s/Carrier63.pdf

[revenant]

Not the exact same animal, but does this give insight into the fate of our molecule.. is it integrated?



http://freepdfhostin.../d6b8364e6f.pdf

Edited by revenant, 10 May 2012 - 05:17 AM.

[niner]

I would suggest a low chronic dosage for large rats, if to be administered on a daily basis. There is no need to consume huge amounts of oil on a daily basis. Possibly 1mL or less of oil per day as a chronic dosage would be sufficient - assuming 3 to 5mg of the original pristine fullerene per mL, depending on your body mass.

This seems reasonable to me. The original rat paper was a long term tox study, not a lifespan study. The effects were seen in a relatively short dosing regimen; i.e., the rats were dosed for a period of time then the dosing stopped, but they went on to live an abnormally long time. Unless there is a saturable elimination mechanism that requires a high dose in order to 'load' the system, I would expect any chronic dosing scheme to work reasonably well.

In the rat paper the C60 was mixed in the dark but I don't understand why this is so important. I could understand no exposing it to direct sunlight full of UV rays but what is wrong with ambient lighting?

Probably nothing. In papers like this, people try to cover all conceivable bases, because they know that everyone is going to nitpick the paper to death once it's published. The same sort of nonsense used to happen in resveratrol papers, where people treated it like it was highly unstable until someone finally published a paper showing that it was a very stable molecule.

Not the exact same animal, but does this give insight into the fate of our molecule.. is it integrated?

No, this isn't covalently attached to a biomolecule. This is a fullerene that has had long alkyl chains synthetically attached to it. One of the chains has a polar head group designed to fix the location of the fullerene in the membrane relative to the surrounding solution. I've seen the term 'lipofullerene' applied both to dendrimer-like alkane-studded fullerenes like the one you posted as well as to a simple solution of C60 in squalane. The use of the term for oil solutions of fullerenes is kind of marketing-speak, if you ask me. Chromatography of an olive oil-fullerene solution would show whether or not the fullerene is forming an adduct with any of the lipid molecules. I'm pretty sure that isn't happening, and that it's just an ordinary solution. Edit: After more study, It looks like C60 does indeed form adducts with the fatty acids in olive oil under the conditions Baati used. I'm updating this in the event that people are reading these early posts. Blue text indicates edits.

The question in my mind is: Do fullerenes react in some way with biomolecules so that they stay in the body permanently, and are not identified by typical analytical methods? The way that they extended life dramatically in the rat paper, even though the dosing stopped completely at a relatively early point in the rats' lives suggests something like this. I have a harder time imagining a mechanism whereby the rat biochemistry was 'reset' from a middle-aged state back to a youthful state, at which point normal aging proceeded, as though a time shift had occurred. At this point, however, I can't think of any obvious mechanisms for a fullerene to react with a biomolecule at body temperature, but I haven't researched the issue. Another possibility is a highly stable physical (non-chemical) interaction that keeps the fullerene located somewhere. Again, nothing is jumping out at me as a mechanism for such an interaction, but that doesn't mean it couldn't happen.

Edit: I now think that it is likely that fullerenes, either free or bound to a fatty acid, may react with another fatty acid in a biological membrane via a Diels-Alder mechanism.

Edited by niner, 28 June 2012 - 05:39 PM.

[Turnbuckle]

I would suggest a low chronic dosage for large rats, if to be administered on a daily basis. There is no need to consume huge amounts of oil on a daily basis. Possibly 1mL or less of oil per day as a chronic dosage would be sufficient - assuming 3 to 5mg of the original pristine fullerene per mL, depending on your body mass.

This seems reasonable to me. The original rat paper was a long term tox study, not a lifespan study. The effects were seen in a relatively short dosing regimen; i.e., the rats were dosed for a period of time then the dosing stopped, but they went on to live an abnormally long time. Unless there is a saturable elimination mechanism that requires a high dose in order to 'load' the system, I would expect any chronic dosing scheme to work reasonably well.

Is it an anti-oxidant effect or a resetting effect to a younger age? While C60 may be a very effective anti-oxidant, the rat trial indicates that it can't be the source of the longer life. If it was, then you'd expect the rats to live only seven months longer, at most. My experience suggests that something additional happens after you stop taking it and that perhaps you need to stop taking it to get the full benefits. So if anyone does another animal trail, a chronic vs episodic dosing might be interesting.

[Junk Master]

Totally agree that an episodic dosing trial would be very interesting. IMO any anti-oxidant should be taken episodically. If you take two grams of vitamin C after a weight workout, or hard aerobic training, you reduce the compensatory adaptation that occurs, and as a result do not get as much benefit.

There's a fine line between stress inducing positive adaptation and overtraining.

[niner]

Interesting. Sounds like they got the idea from this forum. I say the more power to them. Will the FDA allow this to be sold?

IMO, the FDA will crush this, especially if it proves to be beneficial to human health.

I don't think that being beneficial will make them want to crush it; the people who work there are human and will probably want to take it themselves. The law will make them want to crush it, and C60 getting popular will bring it to their attention. As long as it remains on the fringe, I think it will slip under the radar. If the rat experiments are replicated, then look out. I could envision a big price increase for C60, or vendors refusing to sell to individuals for fear of liability in case something goes wrong. If it were to pan out that C60 was a magical fountain of youth for humans, then things would get strange quickly. I could see insurance companies crying foul on annuities, and canceling or modifying the terms of them. Social Security would have a problem. Medicare might actually be helped; that's a harder call. However, even speculating that human lifespan would be nearly doubled the way the rats may or may not have been is kind of crazy, because the normal lifespan for rats is so short. They age more rapidly than we do because they lack some aspect of our biology. The most likely scenario is that if fullerenes really do extend rat lifespan, they are compensating for something that the rat lacks, but that we already have. Thus I really wouldn't expect to see humans regularly living to 150 due to C60 alone. OTOH, I wouldn't be shocked if there were a 'significant' increase in our lifespan and healthspan.

Edited by niner, 11 May 2012 - 11:06 AM.

[HappyPhysicist]

Niner, I couldn't agree more. If C60 does significantly increase human lifespans then all hell is going to break loose. Now, even though I am taking it I sincerely doubt this will be the case.

This would make a great science fiction novel.

[Junk Master]

All C60 would have to do to cause huge publicity, FDA fallout, is to increase aerobic performance even 10 percent. That would virtually force every athlete in the mid, long distance events to had to take it or lose. Every record would be broken, and WADA would be forced to rule on it.

If they banned it, it would be acknowledging it DID improve performance, and then the FDA would have to ban it.

[Turnbuckle]

Here’s a sketchy hypotheses of how C60 might work:

• Fullerenes wrapped in oil are transported to mitochondria for burning.
• Once there, the oil is stripped and the naked fullerenes are attracted to other hydrophobic molecules, such as the methyl groups on the mitochondrial DNA, and reacts with them, stripping them from the DNA.
• Demethylation of the DNA thus reverses the epigenetic DNA changes that result in dysfunction of the mitochondria.

[revenant]

Here’s a sketchy hypotheses of how C60 might work:

• Fullerenes wrapped in oil are transported to mitochondria for burning.
• Once there, the oil is stripped and the naked fullerenes are attracted to other hydrophobic molecules, such as the methyl groups on the mitochondrial DNA, and reacts with them, stripping them from the DNA.
• Demethylation of the DNA thus reverses the epigenetic DNA changes that result in dysfunction of the mitochondria.

That would be amazing if C60 reversed epigenetic modification of the mtDNA. I was thinking along the lines of alterations within the ETC.

IMO, the FDA will crush this, especially if it proves to be beneficial to human health.

I have already started to work up a parts list for a large arc-reactor and purification apparatus. I am gathering as much information I can on this topic. The only high cost I see in producing C60 for consumption is having HPLC assays run on the batches. The process is remarkably simple, really.

[Turnbuckle]

That would be amazing if C60 reversed epigenetic modification of the mtDNA. I was thinking along the lines of alterations within the ETC.

How else could the effect be so long lasting?

[revenant]

That would be amazing if C60 reversed epigenetic modification of the mtDNA. I was thinking along the lines of alterations within the ETC.

How else could the effect be so long lasting?

You have a good point. Seems like the C60 would also be attracted by the phospholipids of the inner membrane after catabolism.

[zorba990]

Here’s a sketchy hypotheses of how C60 might work:

• Fullerenes wrapped in oil are transported to mitochondria for burning.
• Once there, the oil is stripped and the naked fullerenes are attracted to other hydrophobic molecules, such as the methyl groups on the mitochondrial DNA, and reacts with them, stripping them from the DNA.
• Demethylation of the DNA thus reverses the epigenetic DNA changes that result in dysfunction of the mitochondria.

Isn't this something that could be quickly tested in vitro?

[Turnbuckle]

Here’s a sketchy hypotheses of how C60 might work:

• Fullerenes wrapped in oil are transported to mitochondria for burning.
• Once there, the oil is stripped and the naked fullerenes are attracted to other hydrophobic molecules, such as the methyl groups on the mitochondrial DNA, and reacts with them, stripping them from the DNA.
• Demethylation of the DNA thus reverses the epigenetic DNA changes that result in dysfunction of the mitochondria.

Isn't this something that could be quickly tested in vitro?

Mitochondrial DNA isolation techniques are available as are tests for DNA methylation. So sure.

[niner]

Here’s a sketchy hypotheses of how C60 might work:

• Fullerenes wrapped in oil are transported to mitochondria for burning.
• Once there, the oil is stripped and the naked fullerenes are attracted to other hydrophobic molecules, such as the methyl groups on the mitochondrial DNA, and reacts with them, stripping them from the DNA.
• Demethylation of the DNA thus reverses the epigenetic DNA changes that result in dysfunction of the mitochondria.

Fullerenes might make their way to the mitochondria, or at least some of them might, but they aren't going to react with methyl groups. From what I've seen, it takes fairly gnarly reagents and/or extreme conditions to get fullerenes to react. I would look toward a more physical explanation, rather than a chemical one. For example, maybe they lodge in membranes and just stay there. They're total greaseballs, after all; they are going to like hydrocarbons and abhor the aqueous phase. [Edit: not so- see posts below. They do react pretty easily with various fatty acids. Thus they probably do lodge in membranes, but it is a chemical process rather than strictly physical. I still don't see them reacting with methyl groups.]

There's been some mention of mitochondrial biogenesis in this thread... Is this something that fullerenes are known to do? Mitochodrial biogenesis means the creation of new mitochondria; this is under the control of a handful of genes; resveratrol is known to affect these pathways, but I don't see how fullerenes would do it. That doesn't mean they don't- it just strikes me as an unlikely effect. In truth, I don't think anyone knows for sure what is going on with C60 in vivo. A plausible speculation is that they are acting as antioxidants, but something tells me there will end up being more to the story. It will probably take years to figure out the biological mechanisms of action. Look at how long it's taken to get to where we are today with resveratrol, and there's probably still a lot to be learned there.

Edited by niner, 12 May 2012 - 06:30 PM.

[Turnbuckle]

Here’s a sketchy hypotheses of how C60 might work:

• Fullerenes wrapped in oil are transported to mitochondria for burning.
• Once there, the oil is stripped and the naked fullerenes are attracted to other hydrophobic molecules, such as the methyl groups on the mitochondrial DNA, and reacts with them, stripping them from the DNA.
• Demethylation of the DNA thus reverses the epigenetic DNA changes that result in dysfunction of the mitochondria.

Fullerenes might make their way to the mitochondria, or at least some of them might, but they aren't going to react with methyl groups. From what I've seen, it takes fairly gnarly reagents and/or extreme conditions to get fullerenes to react. I would look toward a more physical explanation, rather than a chemical one. For example, maybe they lodge in membranes and just stay there. They're total greaseballs, after all; they are going to like hydrocarbons and abhor the aqueous phase.

There's been some mention of mitochondrial biogenesis in this thread... Is this something that fullerenes are known to do? Mitochodrial biogenesis means the creation of new mitochondria; this is under the control of a handful of genes; resveratrol is known to affect these pathways, but I don't see how fullerenes would do it. That doesn't mean they don't- it just strikes me as an unlikely effect. In truth, I don't think anyone knows for sure what is going on with C60 in vivo. A plausible speculation is that they are acting as antioxidants, but something tells me there will end up being more to the story. It will probably take years to figure out the biological mechanisms of action. Look at how long it's taken to get to where we are today with resveratrol, and there's probably still a lot to be learned there.

It's only an hypothesis, niner. However, even aqueous fullerenes are known to end up in the mitochondria where they are very good antioxidants. See--

http://gr.xjtu.edu.c...dysfunction.pdf

You would not expect them to keep working as antioxidants for years after they have been cleared from the body, however. As for biogenesis, I agree that it's unlikely, and I never said this. I did mention that PQQ has been marketed as promoting mitochondrial biogenesis, and I take it and recommend it as a supplement. But C60 is an entirely different animal.

So that leaves the mystery of how fullerenes, with just a short exposure time, could extend longevity. And also the mystery of how, in just a few hours, it improved my own oxygen utilization, which persists even after I stopped taking it. Fullerenes are known to like methyl groups, and that they could steal them from DNA would certainly provide a tidy explanation of how this works.

[Metrodorus]

It is not the case that fullerene is inert in the olive oil. it does react.

"The stability of C₆₀ and C₇₀ solutions in vegetable oils has been studied in air and under inert atmosphere, after thermal processing and under the action of UV radiation. In all cases it has been found that C₆₀ and C₇₀ are prone to form adducts with the fatty acid chains of the vegetable oils. The adducts are formed both by radical and Diels-Alder mechanisms. "

http://www.springerl...687lk227584231/

Also:

Unsaturated lipids when exposed to air at room temperature undergo a slow autoxidation. When fullereneC₆₀ was dissolved in selected lipids (ethyl oleate, ethyl linoleate, linseed oil and castor oil) the spectrophotometric analysis shows that the oxidation is concentrated to C₆₀ which is converted to an epoxide C₆₀O. Thus, fullerene C₆₀ displays antioxidant activity not only when dissolved in unsaturated lipids but also, more generally, when dissolved in unsaturated solvents subjected to autoxidation.
http://www.sciencedi...009308410000496

Edited by Metrodorus, 12 May 2012 - 03:04 PM.

[Metrodorus]

Solubility and reactions of Fullerene in oil
Cataldo

Full pdf here.

[niner]

It is not the case that fullerene is inert in the olive oil. it does react.

"The stability of C₆₀ and C₇₀ solutions in vegetable oils has been studied in air and under inert atmosphere, after thermal processing and under the action of UV radiation. In all cases it has been found that C₆₀ and C₇₀ are prone to form adducts with the fatty acid chains of the vegetable oils. The adducts are formed both by radical and Diels-Alder mechanisms. "

http://www.springerl...687lk227584231/

Also:

Unsaturated lipids when exposed to air at room temperature undergo a slow autoxidation. When fullereneC₆₀ was dissolved in selected lipids (ethyl oleate, ethyl linoleate, linseed oil and castor oil) the spectrophotometric analysis shows that the oxidation is concentrated to C₆₀ which is converted to an epoxide C₆₀O. Thus, fullerene C₆₀ displays antioxidant activity not only when dissolved in unsaturated lipids but also, more generally, when dissolved in unsaturated solvents subjected to autoxidation.
http://www.sciencedi...009308410000496

Thanks for those refs, Metrodorus. I stand corrected. I agree with Cataldo in that it's kind of a surprising result. This is actually a good thing, as it answers the question of how the C60 can keep on working after the animal stops taking it. If it binds covalently to a fatty acid, then it would form a compound reminiscent of SkQ1, where you have an antioxidant moiety tethered to a polar head group. Structures like this would be likely to lodge in membranes and stay there for an extended amount of time. The proof of this would be finding such compounds in animals that had been given C60 in the past. It would stand to reason that some fatty acids would be better than others. You'd want to optimize the distance between the C60 and the head group. Maybe the oleic acid in olive oil is just right for mitochondria? Time will tell.

[niner]

While we certainly need to see replication in rats and other higher animals using the C60 olive oil solution, there are some existing papers in the literature that find enhanced lifespan with other fullerene compounds. For example, this paper, which looks at the environmental consequences of polyhydroxy fullerene in four different aquatic species finds growth enhancement across the board, and in daphnia, an invertebrate but the most 'animal-like' of the species they looked at, they saw a 38% increase in lifespan.

PLoS One. 2011;6(5):e19976. Epub 2011 May 27.
Polyhydroxy fullerenes (fullerols or fullerenols): beneficial effects on growth and lifespan in diverse biological models.
Gao J, Wang Y, Folta KM, Krishna V, Bai W, Indeglia P, Georgieva A, Nakamura H, Koopman B, Moudgil B.

Particle Engineering Research Center, University of Florida, Gainesville, Florida, United States of America. dencyl@ufl.edu

Recent toxicological studies on carbon nanomaterials, including fullerenes, have led to concerns about their safety. Functionalized fullerenes, such as polyhydroxy fullerenes (PHF, fullerols, or fullerenols), have attracted particular attention due to their water solubility and toxicity. Here, we report surprisingly beneficial and/or specific effects of PHF on model organisms representing four kingdoms, including the green algae Pseudokirchneriella subcapitata, the plant Arabidopsis thaliana, the fungus Aspergillus niger, and the invertebrate Ceriodaphnia dubia. The results showed that PHF had no acute or chronic negative effects on the freshwater organisms. Conversely, PHF could surprisingly increase the algal culture density over controls at higher concentrations (i.e., 72% increase by 1 and 5 mg/L of PHF) and extend the lifespan and stimulate the reproduction of Daphnia (e.g. about 38% by 20 mg/L of PHF). We also show that at certain PHF concentrations fungal growth can be enhanced and Arabidopsis thaliana seedlings exhibit longer hypocotyls, while other complex physiological processes remain unaffected. These findings may open new research fields in the potential applications of PHF, e.g., in biofuel production and aquaculture. These results will form the basis of further research into the mechanisms of growth stimulation and life extension by PHF.

PMID: 21637768
PMCID: PMC3103525 Free PMC Article

Another paper finds that polyhydroxy C60 protects mice from radiation-induced mitochondrial dysfunction. Then there was this one, which reports lifespan extension in wild-type mice from a carboxy-fullerene "SOD Mimetic". I haven't seen the full text of that one, and don't have any details. If anyone has access, that would be great to see. This is beginning to be a body of evidence. Most of the work has been done with fullerenes that have been made water soluble by addition of hydrophilic groups, but a 'membrane soluble' fatty acid adduct should be even better. All this is making the extraordinary claim of nearly doubled mouse lifespan a lot easier to swallow.

[Turnbuckle]

A paper on the epigenetics of aging (it refers to the effects of calorie restriction (CR) on nuclear DNA)--

http://www.biomedcen.../1741-7015/9/98

The evidence suggests that the biological effects of CR are closely related to chromatin function. In fact, acting as an important environmental intervention, CR is speculated to exert its aging-delaying effect through its capacity to increase genomic stability. Reversal of aberrant DNA methylation during aging is believed to be the most effective mechanism for CR to maintain chromatin function and subsequently influence aging processes.

As discussed previously, two major changes in DNA methylation occur during aging progression. These changes involve globally decreased but locally increased DNA methylation status. Interestingly, CR is likely to recover these aging-induced aberrant DNA methylation patterns, but by specific loci control rather than globally.

Another paper says this of the aging of a particular type of human cell type: Therefore, the pattern of methylation in endogenous gene regions appears to undergo random drift during replication of diploid fibroblasts.

So that could be the value of a short treatment time--assuming C60 can function to remove methyl groups--eliminating mtDNA methylation, after which the methylation is reset to its original (and non-aberrant) pattern.

Edited by Turnbuckle, 12 May 2012 - 10:28 PM.

[testerer]

Then there was this one, which reports lifespan extension in wild-type mice from a carboxy-fullerene "SOD Mimetic".

This paper references another one from 2004 called "A BIOLOGICALLY EFFECTIVE FULLERENE (C60) DERIVATIVE WITH SUPEROXIDE DISMUTASE MIMETIC PROPERTIES".

This 2003-2004 paper used a compound called C3, a tris-malonic acid derivative of C60 (tris-malonyl-C60), also called carboxyfullerene. Mutant "Sod2 -/-" mice, lacking expression of mitochondrial manganese superoxide dismutase (MnSOD) had their life span increased by 300% by C3 treatment, suggesting SOD mimetic properties of C3.

They reference two papers about the synthesis of C3:

One is "The e,e,e-family of methanofulllerene(60)-63-carboxylic acids: synthesis, characterization and mass spectroscopy" by Lovett et al
Another one is "Carboxyfullerenes as neuroprotective agents" by Dugan et al (same authors as main 2006 paper)

The first one is hard to come by.
Second one details steps for synthesis of the C3(e,e,e-C60(C(COOH)2)3), the C3-symmetric C60 derivative. Second one also points out that C3 delayed both death and functional deterioration of the test mice. The delay was minor (on the order of 6-7%) but significant statistically.

Returning to main 2006 paper, they administered C3 at 10mg/kg/day starting at 12months of age, by placing C3 in the drinking water. They verified previously (unpublished) that C3 crosses blood-brain barrier. The result was a 11% increase of average life-span (~24.8 to ~27.6 months) and 5% increase of longest lifespan (32,32,32 to 35,35,36). They also found that on spatial learning and memory tests (Morris water maze) C3-treated old mice (23-26 months) gave similar performance as young (6 months) mice, in contrast to control old mice which faired 30 to 60 percent worse than young.

[testerer]

The same authors also released another study in 2008, which also details the necessary steps to create the C3 compound:

"SOD Activity of carboxyfullerenes predicts their neuroprotective efficacy: a structure-activity study"

http://www.sciencedi...54996340800083X

The paper compares different compounds in vitro and finds C3 to be the best practical compound for neuroprotection among others surveyed.

Edited by testerer, 13 May 2012 - 01:07 AM.