Some posts have been deleted. Reminder of thread rules in the 1st entry and post #376.
C60 in olive oil mediated life extension: Scientific discussions
#451
Posted 10 October 2014 - 01:16 PM
#452
Posted 22 October 2014 - 11:19 AM
Have been checking regularly for new publications on Google scholar this year for followups on the c60 rat trial (C60 chronic toxicity study). It's almost 3 years since these trials. Anyone know of any unpublished tech reports or some interim results?
ta
Koala Muncher
#453
Posted 22 October 2014 - 05:57 PM
There's a study ongoing in Kiev, and there is a crowdfunded study into the effect of C60 on cancer in mice.
http://www.longecity...-lifespan-study
#454
Posted 22 October 2014 - 07:00 PM
Here are some that might be related. I'm not qualified to say how much they matter, but I think they are suggestive of "something" going on. At least this stuff in various preparations is not some lethal posion.
Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system
http://www.ncbi.nlm....les/PMC4010637/
Mitochondria-targeted antioxidants and metabolic modulators as pharmacological interventions to slow ageing
http://www.sciencedi...734975012001553
Effects of fullerenol nanoparticles on acetamiprid induced cytoxicity and genotoxicity in cultured human lung fibroblasts
http://www.sciencedi...048357514001321
C70-Carboxyfullerenes as Efficient Antioxidants to Protect Cells against Oxidative-Induced Stress
http://pubs.acs.org/....1021/am4033372
#455
Posted 28 October 2014 - 10:23 AM
One thing that worries me is that the rats lived inside a laboratory with clean air. Is it possible that pollution, smoke and other things like that which normal people are constantly exposed to may react with c60 in the lungs? Has there been any kind of information or research in this direction? I can't find anything in the c60 literature.
#456
Posted 28 October 2014 - 12:38 PM
One thing that worries me is that the rats lived inside a laboratory with clean air. Is it possible that pollution, smoke and other things like that which normal people are constantly exposed to may react with c60 in the lungs? Has there been any kind of information or research in this direction? I can't find anything in the c60 literature.
You have to consider a number things- what's likely to get into the lungs, where does it go, where does c60-oo exist in the body, what kind of chemistry is possible with fullerenes, and finally, would the reaction product be harmful. Without going into any detail whatsoever, my analysis of all of these things tells me that c60-oo is more likely to help you under pollution exposure than to hurt you, but that it's not a magic shield. You should avoid high toxicity environments whether you use c60oo or not, and if you are doing something that creates dust, wear the appropriate level of protection. (The 3M 6000 series respirator with P100 particulate cartridges is the nicest non-powered respirator I've ever used. I just got this setup recently and love it.)
#457
Posted 03 November 2014 - 08:57 AM
Ok, a recent study confirming that 30 extreme doses (at 2000mg /kg) (compare this to the 0.02mg/kg that humans seem to be taking) don't disturb the full blood picture or electrolytes and also the c60 didn't accumulate in the organs of rats. Also, it didn't kill the rats. This is consistent with the prior results of c60 having low toxicity. So far it looks like we haven't found a LD50 for C60; this is a good thing.
http://www.tandfonli...95#.VFdBpfmUd8E
"In this study, male rats were intragastrically exposed to fullerene C60 for 1-day and 30-day periods at daily doses of 2000 and 250 mg/kg of body weight, respectively. Fullerene was detected in organs and tissues by HPLC after the extraction from biosamples with toluene. No statistically significant differences in hematological and biochemical parameters of control and treated rats were found after single and multiple administrations. Throughout the observation periods no lethality was observed. At necropsy, no pathomorphological changes in internal organs were recorded. Fullerene was found in stomach, small intestine, liver, lungs, spleen, kidneys, and blood. The amounts of the detected fullerene in comparison to the administered doses are far smaller which is the evidence of its efficient excretion. Hence, it can be assumed that fullerene nanoparticles penetrate from the gastrointestinal tract of rats into the bloodstream and translocate into secondary organs with no pronounced toxic effect in experimental conditions studied."
Edited by koala_muncher, 03 November 2014 - 09:11 AM.
#458
Posted 03 November 2014 - 12:52 PM
Ok, a recent study confirming that 30 extreme doses (at 2000mg /kg) (compare this to the 0.02mg/kg that humans seem to be taking) don't disturb the full blood picture or electrolytes and also the c60 didn't accumulate in the organs of rats. Also, it didn't kill the rats. This is consistent with the prior results of c60 having low toxicity. So far it looks like we haven't found a LD50 for C60; this is a good thing.
http://www.tandfonli...95#.VFdBpfmUd8E
"In this study, male rats were intragastrically exposed to fullerene C60 for 1-day and 30-day periods at daily doses of 2000 and 250 mg/kg of body weight, respectively. Fullerene was detected in organs and tissues by HPLC after the extraction from biosamples with toluene. No statistically significant differences in hematological and biochemical parameters of control and treated rats were found after single and multiple administrations. Throughout the observation periods no lethality was observed. At necropsy, no pathomorphological changes in internal organs were recorded. Fullerene was found in stomach, small intestine, liver, lungs, spleen, kidneys, and blood. The amounts of the detected fullerene in comparison to the administered doses are far smaller which is the evidence of its efficient excretion. Hence, it can be assumed that fullerene nanoparticles penetrate from the gastrointestinal tract of rats into the bloodstream and translocate into secondary organs with no pronounced toxic effect in experimental conditions studied."
Wow, those were megadoses! The question is, what form was it? That usually makes a lot of difference. Anyone have access to the full text?
#459
Posted 03 November 2014 - 01:47 PM
So far it looks like we haven't found a LD50 for C60; this is a good thing.
This isn't relevant to C60evoo. The only way to get this dosage into a rat is to employ nC60, where n is rather large. So it's like feeding rats sand in their food and then making a generalization to fumed silica. Judging by the journal, however--Fullerenes, Nanotubes and Carbon Nanostructures--the thrust of this work is to show that C60 powder is not dangerous in industrial environments, not to demonstrate its safety as a drug.
Edited by Turnbuckle, 03 November 2014 - 02:16 PM.
#460
Posted 03 November 2014 - 02:57 PM
So far it looks like we haven't found a LD50 for C60; this is a good thing.
This isn't relevant to C60evoo. The only way to get this dosage into a rat is to employ nC60, where n is rather large. So it's like feeding rats sand in their food and then making a generalization to fumed silica. Judging by the journal, however--Fullerenes, Nanotubes and Carbon Nanostructures--the thrust of this work is to show that C60 powder is not dangerous in industrial environments, not to demonstrate its safety as a drug.
It shows that centrifuging and whatever isn't necessary doesn't it? I'll see if I can find full text via my employers system but it's hopeless a mess of a joke so I might be unable to dig this out. Will give it a try later today.
#461
Posted 03 November 2014 - 03:26 PM
So far it looks like we haven't found a LD50 for C60; this is a good thing.
This isn't relevant to C60evoo. The only way to get this dosage into a rat is to employ nC60, where n is rather large. So it's like feeding rats sand in their food and then making a generalization to fumed silica. Judging by the journal, however--Fullerenes, Nanotubes and Carbon Nanostructures--the thrust of this work is to show that C60 powder is not dangerous in industrial environments, not to demonstrate its safety as a drug.
It shows that centrifuging and whatever isn't necessary doesn't it? I'll see if I can find full text via my employers system but it's hopeless a mess of a joke so I might be unable to dig this out. Will give it a try later today.
It shows that rats will live as much as 30 days without significant changes in the parameters tested.
#462
Posted 03 November 2014 - 03:50 PM
Another recent C60 paper is very interesting from the standpoint of memory--
The role of low levels of fullerene C60 nanocrystals on enhanced learning and memory of rats through persistent CaMKII activation.
Engineered nanomaterials are known to exhibit diverse and sometimes unexpected biological effects. Fullerene nanoparticles have been reported to specifically bind to and elicit persistent activation of hippocampal Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), a multimeric intracellular serine/threonine kinase central to Ca(2+) signal transduction and critical for synaptic plasticity, but the functional consequence of that modulation is unknown. Here we show that low doses of fullerene C60 nanocrystals (Nano C60), delivered through intrahippocampal infusion and without any obvious cytotoxicity in hippocampal neuronal cells, enhance the long-term potentiation (LTP) of rats. Intraperitoneal injection of 320 μg/kg of Nano C60, once daily for 10 days, also enhanced spatial memory of rats in addition to an increase of LTP. In parallel, both the IH and IP administration of Nano C60 increased the autonomous activity and the level of threonine 286 (T286) autophosphorylation of CaMKII, enhanced post-synaptic AMPA/NMDA ratio, and triggered time-dependent activation of ERK and CREB. Our results reveal a striking and highly unexpected ability of Nano C60 in positively modulating learning and memory, an effect that is most likely manifested through locking CaMKII in an active conformation, and may have significant implications for the potential therapeutic applications of fullerene C60, a classic engineered nanomaterial.
Neuronal Ca2+/calmodulin-dependent protein kinase II--discovery, progress in a quarter of a century, and perspective: implication for learning and memory.Much has been learned about the activity-dependent synaptic modifications that are thought to underlie memory storage, but the mechanism by which these modifications are stored remains unclear. A good candidate for the storage mechanism is Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). CaM kinase II is one of the most prominent protein kinases, present in essentially every tissue but most concentrated in brain. Although it has been about a quarter of a century since the finding, CaM kinase II has been of the major interest in the region of brain science. It plays a multifunctional role in many intracellular events, and the expression of the enzyme is carefully regulated in brain regions and during brain development. Neuronal CaM kinase II regulates important neuronal functions, including neurotransmitter synthesis, neurotransmitter release, modulation of ion channel activity, cellular transport, cell morphology and neurite extension, synaptic plasticity, learning and memory, and gene expression. Studies concerning this kinase have provided insight into the molecular basis of nerve functions, especially learning and memory, and indicate one direction for studies in the field of neuroscience. This review presents the molecular structure, properties and functions of CaM kinase II, as a major component of neurons, based mainly developed on findings made in our laboratory.
https://www.jstage.j.../28_8_1342/_pdf
The spherical C60 molecule would seem ideal for an interaction with this kinase geometry (just as with UCP2 in the mitochondria)--
Attached Files
Edited by Turnbuckle, 03 November 2014 - 04:11 PM.
#463
Posted 03 November 2014 - 03:58 PM
I too saw a couple of papers slip by while browsing the 2015 archives, some of them seemed promising though they related to different types of formulation. I did see the phrase neuroprotective more than once. I can't find them now but will try tomorrow back at work.
#464
Posted 03 November 2014 - 05:45 PM
Found a bunch of papers, I'm sure some of them have been posted before but I can't recall seeing some of these here. They relate to different types of C60.
The applications of buckminsterfullerene C60 and derivatives in orthopaedic research.
http://www.ncbi.nlm....pubmed/24409811
Pristine C(60) fullerenes inhibit the rate of tumor growth and metastasis.
http://www.ncbi.nlm....pubmed/21956470
Comparison of anti-angiogenic properties of pristine carbon nanoparticles
http://www.nanoscale...content/8/1/195
Nanoparticles of carbon allotropes inhibit glioblastoma multiforme angiogenesis in ovo
http://www.dovepress...wed-article-IJN
Shape Effect of Carbon Nanovectors on Angiogenesis
http://pubs.acs.org/....1021/nn901465h
A Cationic [60] Fullerene Derivative Reduces Invasion and Migration of HT-29 CRC Cells in Vitro at Dose Free of Significant Effects on Cell Survival
http://www.nmletters...n-cell-survival#
Reduction of conspicuous facial pores by topical fullerene: possible role in the suppression of PGE2 production in the skin
http://www.jnanobiot.../content/12/1/6
[60]Fullerene derivative modulates adenosine and metabotropic glutamate receptors gene expression: a possible protective effect against hypoxia
http://www.jnanobiot...content/12/1/27
Interaction of fullerene nanoparticles with biomembranes: from the partition in lipid membranes to effects on mitochondrial bioenergetics.
http://www.ncbi.nlm....pubmed/24361870
Photodynamic anti-cancer effects of fullerene [C₆₀]-PEG complex on fibrosarcomas preferentially over normal fibroblasts in terms of fullerene uptake and cytotoxicity.
http://www.ncbi.nlm....pubmed/24496749
#465
Posted 04 November 2014 - 04:34 AM
Ok, a recent study confirming that 30 extreme doses (at 2000mg /kg) (compare this to the 0.02mg/kg that humans seem to be taking) don't disturb the full blood picture or electrolytes and also the c60 didn't accumulate in the organs of rats. Also, it didn't kill the rats. This is consistent with the prior results of c60 having low toxicity. So far it looks like we haven't found a LD50 for C60; this is a good thing.
http://www.tandfonli...95#.VFdBpfmUd8E
"In this study, male rats were intragastrically exposed to fullerene C60 for 1-day and 30-day periods at daily doses of 2000 and 250 mg/kg of body weight, respectively. Fullerene was detected in organs and tissues by HPLC after the extraction from biosamples with toluene. No statistically significant differences in hematological and biochemical parameters of control and treated rats were found after single and multiple administrations. Throughout the observation periods no lethality was observed. At necropsy, no pathomorphological changes in internal organs were recorded. Fullerene was found in stomach, small intestine, liver, lungs, spleen, kidneys, and blood. The amounts of the detected fullerene in comparison to the administered doses are far smaller which is the evidence of its efficient excretion. Hence, it can be assumed that fullerene nanoparticles penetrate from the gastrointestinal tract of rats into the bloodstream and translocate into secondary organs with no pronounced toxic effect in experimental conditions studied."
Wow, those were megadoses! The question is, what form was it? That usually makes a lot of difference. Anyone have access to the full text?
FULL TEXT: http://www.tandfonli...83X.2014.949695
#466
Posted 04 November 2014 - 05:25 AM
Not working for me. Can you read it and say what form they used.
#467
Posted 04 November 2014 - 12:16 PM
The file might not open on some computers, so here are the relevant parts--
2.3 Preparation of Fullerene C60 Dispersions for Administration to AnimalsA weighed sample of fullerene was triturated with a 1% aqueous solution of starch containing 0.1% Tween-80. The dispersion was sonicated for 5 min using a Sonopuls HD 3100 ultrasonic homogenizer (Bandelin, Germany). Animals were exposed to dispersions of C60 no later than 15 min after the preparation.
This method is unlikely to produce any dissolved C60 whatsoever. So what is being tested here is nC60 in a dispersed powder form, where n is large.
2.4 Experimental DesignThe maximum tolerated dose of fullerene was determined in experiments performed for 14 days. The doses were 1000, 2000, 3000, 4000, and 5000 mg/kg of body weight. In the case of exposure to single and multiple doses of fullerene, the duration of the experiments was 1 and 30 days, respectively. The dose used for the single exposure was 2000 mg/kg of body weight; for multiple exposures, the daily dose was 250 mg/kg of body weight over a 30-day period.
Edited by Turnbuckle, 04 November 2014 - 01:00 PM.
#468
Posted 04 November 2014 - 01:36 PM
Attached Files
#469
Posted 14 November 2014 - 07:58 AM
Interesting post on FA today about stem cells and the lungs. The FA post is not specifically about c60.
But there was a previous c60 discussion here related to possible improved lung capacity.
The Lung Can Regenerate
https://www.fightagi...-regenerate.php
#470
Posted 16 November 2014 - 11:27 PM
I came across a 2014 paper today that set out to find out if Baati's results could be justified computationally, assuming mitochondrial activity of fullerene.
The paper title is "Can C60 fullerene demonstrate properties of mitochondria-targeted antioxidant from the computational point of view?"
INTERNATIONAL JOURNAL OF BIOLOGY AND BIOMEDICAL ENGINEERING Volume 8, 2014
Abstract— Theoretical examination of one hypothesis explaining fullerene C60 anti-oxidant potential has been done with Density Functional Theory (DFT). We found that a mechanism involving fullerene-mediated proton transport through inner mitohondria membrane is feasible from the computational point of view.
#471
Posted 17 November 2014 - 07:57 AM
Great reference Metrodorus.
Here's my summary:
- The authors propose that C60 may reduce the mitochondrial production of superoxide by decreasing the charge potential across the mitochondrial membrane.
- A 10% decrease in such potential reduces superoxide by a factor of 10.
- Too much decrease in potential is toxic.
- The authors did not say this, but it would make sense that it may be possible to overdose on C60, reduce the mitochondrial membrane potential by too much, and cause problems such as reduced ATP synthesis.
- They did a quantum-mechanical analysis of C60 either alone or surrounded by water molecules to determine whether it can absorb protons
- They found that each C60 molecule can absorb (contain) up to 6 protons and that this wasn't influenced by surrounding water molecules.
- They did not model C60 with lipids.
So the good news is that there's now support for the idea that C60 could work to reduce mitochondrial production of superoxides, and therefore extend life.
The bad news is that it may be dose-critical, and a too-high dose may be damaging.
#472
Posted 17 November 2014 - 08:55 AM
Great reference Metrodorus.
Here's my summary:
- The authors propose that C60 may reduce the mitochondrial production of superoxide by decreasing the charge potential across the mitochondrial membrane.
- A 10% decrease in such potential reduces superoxide by a factor of 10.
- Too much decrease in potential is toxic.
- The authors did not say this, but it would make sense that it may be possible to overdose on C60, reduce the mitochondrial membrane potential by too much, and cause problems such as reduced ATP synthesis.
- They did a quantum-mechanical analysis of C60 either alone or surrounded by water molecules to determine whether it can absorb protons
- They found that each C60 molecule can absorb (contain) up to 6 protons and that this wasn't influenced by surrounding water molecules.
- They did not model C60 with lipids.
So the good news is that there's now support for the idea that C60 could work to reduce mitochondrial production of superoxides, and therefore extend life.
The bad news is that it may be dose-critical, and a too-high dose may be damaging.
A key question is then whether or not a large dose of C60 will decrease the charge potential across the mitochondrial membrane more than a smaller dose. We have not seen any toxicity, so it may be that there is a limiting effect, or that the dose required for a toxic decrease in potential is very high.
#473
Posted 17 November 2014 - 01:57 PM
A paper which shows that hydrogen inside C60 increases the quenching rate for singlet oxygen--Can H2 Inside C60 Communicate with the Outside World? The attached plot is from that paper, showing the difference between empty C60 and C60 containing hydrogen (blue) or deuterium (red).
Attached Files
#474
Posted 18 November 2014 - 01:16 AM
I came across a 2014 paper today that set out to find out if Baati's results could be justified computationally, assuming mitochondrial activity of fullerene.
The paper title is "Can C60 fullerene demonstrate properties of mitochondria-targeted antioxidant from the computational point of view?"
INTERNATIONAL JOURNAL OF BIOLOGY AND BIOMEDICAL ENGINEERING Volume 8, 2014
Abstract— Theoretical examination of one hypothesis explaining fullerene C60 anti-oxidant potential has been done with Density Functional Theory (DFT). We found that a mechanism involving fullerene-mediated proton transport through inner mitohondria membrane is feasible from the computational point of view.
This paper is a re-hash of Chistyakov's 2013 paper that I critiqued in this thread. It's essentially the same stuff, and is barking up the same wrong tree. The main problem is that they are considering the interior of a cell to be similar to the interior of a cyclotron- in that they think there are free protons flying around. In reality, those protons would be bound to water as H3O+. There's just no way that a hydronium ion is going to squeeze its way into 60; in fact just getting a hydrogen molecule in requires that the c60 be created around the hydrogen by organic synthesis. Their mild uncoupling idea isn't consistent with in vivo observations in humans. If anything, c60oo appears to be making more, rather than less ATP. C60 analogs have been shown to have superoxide dismutase activity, so there is already a chemically sensible explanation for a reduced level of superoxide. I was excited when I saw the title of their latest paper, but ultimately disappointed.
#475
Posted 04 December 2014 - 10:37 PM
Thanks for that input, niner.
Another useful paper I stumbled across today, is useful mainly because it systematically summarises so much of the recent literature. It does not seem to offer anything new.
http://scholarsresea...-5-3-99-139.pdf
#476
Posted 09 December 2014 - 12:00 AM
I have not read of many primate studies with fullerene. This one from 22 July 2014 seems interesting - particularly from a toxicity perspective.
Annals of NeurologyVolume 76, Issue 3, pages 393–402, September 2014
We evaluated the efficacy of the potent antioxidant C3 to salvage nigrostriatal neuronal function after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure in nonhuman primates. C3 is a first-in-class functionalized water-soluble fullerene that reduces oxygen radical species associated with neurodegeneration in in vitro studies. However, C3 has not been evaluated as a neuroprotective agent in a Parkinson model in vivo.
Macaque fascicularis monkeys were used in a double-blind, placebo-controlled study design. MPTP-lesioned primates were given systemic C3 (n = 8) or placebo (n = 7) for 2 months starting 1 week after MPTP. Outcomes included in vivo behavioral measures of motor parkinsonism using a validated nonhuman primate rating scale, kinematic analyses of peak upper extremity velocity, positron emission tomography imaging of 6-[18F]fluorodopa (FD; reflects dopa decarboxylase) and [11C]dihydrotetrabenazine (DTBZ; reflects vesicular monoamine transporter type 2), ex vivo quantification of striatal dopamine, and stereologic counts of tyrosine hydroxylase–immunostained neurons in substantia nigra.
After 2 months, C3-treated monkeys had significantly improved parkinsonian motor ratings, greater striatal FD and DTBZ uptake, and higher striatal dopamine levels. None of the C3-treated animals developed any toxicity.
Systemic treatment with C3 reduced striatal injury and improved motor function despite administration after the MPTP injury process had begun. These data strongly support further development of C3 as a promising therapeutic agent for Parkinson disease. Ann Neurol
#477
Posted 09 December 2014 - 12:29 PM
Thank you Metrodorus. I had not seen those studies in the past. The paper on fullerene-films is interesting in relation to the discussions on this board about storagetime of C60oo.
#478
Posted 11 December 2014 - 09:11 AM
Yesterday when i was pondering what i read about the immediate effects of c60 (what other people reported and a bit of my own experience), an idea struck me. Could it be that C60 directly affects red blood cells? I read that people taking c60 and donating blood reported unusual red blood color. More oxigenated blood cells could maybe explain the endurance effect a lot of people report (including me).
Since my medical knowledge is not very deep, i am posting this for the experts here to discuss or refute. Thanx for reading.
#479
Posted 11 December 2014 - 03:53 PM
Several large rats have reported effects related to muscle fatigue.
A researcher - possibly coming across these references on a thread such as this, has conducted experiments on rats, giving data to back up these anecdotal reports.
The pdf can be downloaded from here:
http://www.irbis-nbu..._2014_7_3_6.pdf
dynamics of fatigue processes in rat soleus muscle after ischemia-reperfusion injury using
the tensiometric method was studied.
#480
Posted 11 December 2014 - 07:12 PM
That was interesting Metrodorus. The kind of work that I hope gets attention by the medical community. Trying this substance on people whose life are in danger might be easier for an ethical board to recognize. Is there anything we can do to make the medical community aware of this?
What exactly do they mean by C60FAS? If I'm reading it right it's not terribly different from lipofullerenes. IV seemed to be the most effective, but I guess we can afford to stay away from that.
Also tagged with one or more of these keywords: c60, buckyballs, lifespan, baati, moussa, fullerenes
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