Tom Sims [Chicago] Unplugged: Jimmy Carter-ET-Abduction, Trump-Mueller Sting – QAnon-4Chan.com – Carbon60-Bucky Balls- Longevity & Positive AI
WATCH ON ExopoliticsTV: https://youtu.be/c4PO-mi2BpI
C60 Molecule Sculpture in Madison Square Park, New York, NY
VIDEOS REFERENCED IN THE OPENING OF ABOVE INTERVIEW:
“The UFO/ET Abductions of Jimmy Carter, Alfred Lambremont Webre & Andrew D. Basiago:
A Path to A Positive Future for Humanity in Our Galaxy”,
As presented on July 30, 2017 at the First Annual UFO Fest & Symposium, Yelm, WA
WATCH ON ExopoliticsTV: https://youtu.be/DnwFGIPCf60
Now the full hidden history behind 1980 October surprise by the shadow government & Deep State can finally be revealed
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Coast To Coast Host George Noory Cancels Jimmy Carter ET Abduction Story On 100th Anniversary Of JFK’s Birth – [Carter & JFK were half-brothers by some evidence]
By Alfred Lambremont Webre
VANCOUVER, BC – On Sunday May 28, 2017, I was invited over the phone by Lisa Lyons, who has scheduled guests on Coast to Coast for hosts ranging from Art Bell to George Noory, to present my “Jimmy Carter-Alfred Lambremont Webre – Andrew D. Basiago interactive ET Abductions 1969-1975” program to be broadcast on Tuesday-Wednesday May 29-30, 2017 Midnight-2 AM.
My C2C interview was scheduled on the date of the 100th anniversary of John F. Kennedy’s birth. During the interview, I was going to discuss the evidence suggesting that John F. Kennedy and Jimmy Carter may be half-brothers, along with the events where President-Elect Jimmy Carter had sent a special emissary to meet me at the Carlyle Hotel in NYC right after he won the 1976 election and after Rep Henry B. Gonzalez [D-TX] got the House Select Committee on Assassinations approved. Carter’s emissary, from a leading Atlanta GA law firm whose principal partner’s son I went to prep school with in Washington DC, stated that Carter wanted to liaison with the House Select Committee on Assassinations [HSCA] JFK Assassination investigation.
The Jimmy Carter emissary invited me to a dinner on Capitol Hill in Dec. 1976 with Carter insiders, where the concept for the 1977 Carter White House Extraterrestrial Communication study, which I directed, was born.
Hours before the May 29-30, 2017 Coast to Coast AM program was to be broadcast, I called Lisa Lyon who said that George Noory had intervened to cancel my approved and schedule program, saying to Lisa, “No we are not doing that program.”
When I confronted Lisa Lyon on the phone, stating that Tom Danheiser, her co-Producer at Coast to Coast has just called me personally in Vancouver, BC a few weeks earlier to invite me to be interviewed by George Noory in the Boulder, CO studios of GAIA [which I turned down], Lisa said “I apologize Alfred”.
Clearly there was no business as usual justification for George Noory’s cancelling my interview on the Jimmy Carter ET abduction program just hours before broadcast time on Coast to Coast, other than a malevolent ground of censorship.
George Noory: Operative, Clone or AI Robotoid?
I have concluded that George Noory is a functional enemy of authentic ET Disclosure and either (a) an AI Entrained and mind controlled Matrix operative, (b) a dark-side Navy, NSA or other Black Ops clone, or (c) AI Robotoid managed by the AI handlers of GAIA.com and mind control slave of GAIA CEO Jerka Rysavy’s handlers somewhere in the global mind control empire, be that Russia-sponsored KGB-FSB or USA-sponsored NSA or ONI headquarters.
Alfred Lambremont Webre
“OVERTON WINDOW”
OVERTON.WINDOW
TOM SIMS: Jimmy Carter ET Abduction Video, The Overton Window, & Tom Sim’s Video Card
TOM: “Alfred when I clicked to watch your video from Facebook my screen went blank for a sec really hate to say this but looks like YouTube is targeting your viewers with malicious code.
“I have supplicated means of blocking this code so no harm came to my system to other viewers they are not likely targeting people at random only those that deemed a high threat.
“Alfred will know who I am and why they would target me maybe an interview my security is up to the task if done over Skype other services are easier to secure but I have taken measures to secure Skype most of my work is done via subtlety for the better but soon things will be more open for those that consider their selves big players be careful taking precautions is not always gonna be enough to protect you at some point they will get you no security system is perfect.
“A lot of the topics I talked about and the video I commented on because they destroyed my Video Card when I tried to watch is also a big sore spot for the cabal.
“Two separate issues I sense at first they were scared of how I would share the video if I saw it then once you wanted to interview me they were scared of what I would say 2 separate issues the video might not be the tell all just that it hit a few soft spots what I said might not be the big breaking point but it will cause some ripples of some size really good work when we are pissing them off its a good sign not that we should aim to piss off anybody but in this case we really should not care about their feelings as its what we need to say its like an police investigator asking a suspect questions and when the suspect breaks out in a cold sweat when a photo certain piece of evidence the investigator was aiming to make the suspect nervous nor should he have any remorse for doing so the fact it happened is something that will aid in his investigation we have to be somewhat detached from our work as in do not let our feelings slow us down we need to be able to see catastrophe and not focus on any one event nor stop because of it being so intense just because one does not see something does not make it go away it requires us to be strong and requires us to not second guess our selves because we are looking at a slippery slope of morals and ethics.”
TOM SIMS
Tom Sims & the Overton Window
https://en.wikipedia.org/wiki/Overton_window
The Overton window, also known as the window of discourse, is the range of ideas tolerated in public discourse. The term is derived from its originator, Joseph P. Overton, a former vice president of the Mackinac Center for Public Policy, who in his description of his window claimed that an idea’s political viability depends mainly on whether it falls within the window, rather than on politicians’ individual preferences.[1][2] According to Overton’s description, his window includes a range of policies considered politically acceptable in the current climate of public opinion, which a politician can recommend without being considered too extreme to gain or keep public office.
Overton described a spectrum from “more free” to “less free” with regard to government intervention, oriented vertically on an axis, to avoid comparison with the left-right political spectrum.[3] As the spectrum moves or expands, an idea at a given location may become more or less politically acceptable. Political commentator Joshua Treviño postulated that the degrees of acceptance of public ideas are roughly:[4]
- Unthinkable
- Radical
- Acceptable
- Sensible
- Popular
- Policy
The Overton window is an approach to identifying which ideas define the domain of acceptability within a democracy’s possible governmental policies. Proponents of policies outside the window seek to persuade or educate the public in order to move and/or expand the window. Proponents of current policies, or similar ones, within the window seek to convince people that policies outside it should be deemed unacceptable.
After Overton’s death, others have examined the concept of adjusting the window by the deliberate promotion of ideas outside of it, or “outer fringe” ideas, with the intention of making less fringe ideas acceptable by comparison.[5] The “door-in-the-face” technique of persuasion is similar.
c60-green Bucky Ball
Carbon60.Molecule in Madison Square Park
C60 MOLECULE – Bucky Ball & Human Longevity
NEW YORK, NY.- Madison Square Park Conservancy ‘s Mad. Sq. Art program announces a new, monumental sculpture by world-renowned artist Leo Villareal. Largely inspired by the work of Buckminster Fuller, Villareal’s BUCKYBALL will apply concepts of geometry and mathematical relationships within a towering 30-foot tall, illuminated sculpture. The site-specific work will remain on view daily from October 25, 2012 through February 1, 2013 in Madison Square Park.
A commission of the Mad. Sq. Art program, Villareal’s BUCKYBALL will feature two nested, geodesic sculptural spheres comprised of 180 LED tubes arranged in a series of pentagons and hexagons, known as a “Fullerene,” referring to the form’s discovery by Buckminster Fuller. Individual pixels located every 1.2 inches along the tubes are each capable of displaying 16 million distinct colors and will be specifically tuned by the artist’s own software, creating dynamic light sequences that will enliven the natural landscape of the park. Relying on LED technologies driven by chance, BUCKYBALL’s light sequences will create exuberant, random compositions of varied speed, color, opacity, and scale. BUCKYBALL will trigger neurological processes within the brain, calling on our natural impulse to identify patterns and gather meaning from our external environment.
Through basic elements such as pixels and binary codes, Villareal allows for a better understanding of the underlying structures and systems that govern everyday function. As he builds these simple elements into a full-scale sculptural installation that moves, changes, and interacts, the work ultimately grows into a complex, dynamic form that questions common notions of space, time, and sensorial pleasure.
Villareal’s light sculpture will be surrounded by zero-gravity couches that allow viewers to recline below the artwork. These couches are built out of wooden slats that mimic the construction method of adjacent park benches just as the pedestal on which BUCKYBALL rests emulates support structures found within the park’s neighboring sculptural monuments.
Artist Leo Villareal states, “I am thrilled to be presenting BUCKYBALL in Madison Square Park. My new light sculpture takes the form of a Carbon 60 molecule and expands it to monumental scale. It also explores self-similarity through the use of two identical nested spheres, the outer at 20 feet in diameter and the inner at 10 feet. Lined with LED tubes, these structures are activated through sequenced light driven by custom software. This public artwork reinterprets many of the traditional elements found in the park such as seating and historic monuments in a fresh and exciting way.”
Madison Square Park Conservancy President Debbie Landau comments, “Leo’s BUCKYBALL is apt for Madison Square Park’s unique landscape. It shares much in common with the shifting colors and light of the fall season. It will animate the park throughout the fall and winter with its ever-shifting light.”
Installation of Leo Villareal’s BUCKYBALL (2012) underway in Madison Square Park. Image courtesy of the Madison Square Park Conservancy.
Berkeley Lab scientists determine electrical properties of carbon-60 molecular layer
Feature Story • May 12, 2003
Contact: Dan Krotz, DAKrotz@lbl.gov
Using some of the world’s most advanced photoelectron spectroscopy and computing techniques, Berkeley Lab scientists gained a more precise understanding of the electrical properties of fullerenes, those famous soccer-ball-shaped molecules comprised of 60 carbon atoms.
The team, which also includes researchers from Stanford University and Europe, obtained the first experimental measurement of the range of energies possessed by electrons, as a function of their momenta, in a single layer of carbon-60 molecules doped with additional electrons, a step that transforms the molecule into one of the best known superconductors, meaning it conducts electricity without resistance below a certain critical temperature.
http://wowa.artlinkart.com/en/top/detail/3c5ivyr.html
Buckyballs are soccer ball-shaped 60-atom clusters of pure carbon.
As expected in a molecular solid, they found that the electrons’ energy-momentum range, also called the bandwidth, is quite narrow. But they were surprised by how narrow. And when they compared their measurements to theoretical calculations, they determined why.
“We knew the bandwidth was small. But our research reveals, experimentally, that it’s even smaller than anticipated,” says Steven Louie, a theoretical physicist in Berkeley Lab’s Materials Sciences Division and a professor of physics at the University of California at Berkeley. “And we determined that the additional 50-percent reduction is consistent with the effects of electron-phonon interactions.”
Their work, reported in the April 11, 2003, issue of Science, demonstrates how the electronic properties of fullerenes and similar molecules are affected by interactions between electrons and phonons — particles associated with atomic vibrations in a solid. This, in turn, will inform further research on other fullerene properties such as heat capacity and electron transport, possibly laying the groundwork for real-world applications.
A new form of carbon
Discovered in 1985 during experiments on carbon clusters using atomic beams, carbon-60 was named buckminsterfullerene, or buckyball, because it resembles American architect R. Buckminster Fuller’s geodesic domes. Since then scientists have engineered giant fullerenes with as many as 960 carbon atoms, “buckybabies” with 32 atoms, and elongated structures such as nanotubes.
The molecules join diamond and graphite as the only forms of pure carbon, and have been heralded as stars in the burgeoning field of nanoscience, with potential uses as lubricants, drug delivery agents, and superconductors. In particular, researchers remain intrigued over the latter: when a carbon-60 solid is doped by inserting alkali atoms such as potassium into empty spaces within its crystal structure, it becomes superconducting at the relatively high temperature of about 40 degrees Kelvin. Because most conventional superconductors require temperatures at or below 20 degrees Kelvin, doped fullerenes offer a potentially easier way to incorporate zero resistance into electrical systems. Only the high-Tc cuprate superconductors have higher transition temperatures.
More research is needed however. Topping the to-do list is a precise measurement of the molecular solid’s bandwidth. In other words, what is the energy-momentum range of the electrons, from the most tightly bound to the least tightly bound, in a given band? And what factors dictate this range? Based on theoretical calculations (and some indirect experimental evidence) conducted in the 18 years since its discovery, scientists know doped fullerene solids have a narrow bandwidth, and they know this is most likely due to interactions between electrons and phonons. But these theories lacked definitive experimental support.
To obtain this support, the team used Berkeley Lab’s Advanced Light Source (ALS), a synchrotron that emits light in the x-ray region of the electromagnetic spectrum that is one billion times brighter than the sun. They subjected a doped carbon-60 monolayer to these extremely bright x-rays, which bombard the sample with photons. Electrons in the fullerene layer absorb the photons, gain energy, and bounce out of the layer. A detector then records the electrons’ kinetic energies, which indicates the energy level they occupied in the layer. After recording a range of these electrons, the team produced the first photoemission measurement of a doped fullerene layer’s bandwidth and band dispersion, which is the relationship between electron energy versus momentum.
Like running through water
This experimental bandwidth mirrored bandwidths derived from theoretical calculations, except for one important detail. It was 50 percent narrower. This means the electrons observed in the sample possessed less kinetic energy for a given momentum than expected. Or, put another way, they appeared to have more mass. The Berkeley Lab team knew this was an illusion; the electrons don’t possess more mass. Rather, the ALS data captured an interaction between electrons and some other particle that dulls the electrons’ energy-momentum and makes them appear heavier — much like a person trying to run in water will accelerate much more slowly, and seem to have more mass, than when they run on land.
But what acts like water in this case? What particle impairs the electrons’ energy-momentum? Earlier research pointed to one of two culprits: either electron-electron interactions, or electron-phonon interactions. The former phenomenon is easily explained. Because they repel one another, electron interactions make electrons appear heavier.
Phonons, however, are more difficult to grasp. Just as light can behave like a wave, as in an electromagnetic wave, or like a particle, as in a photon, so too can atomic vibrations that reverberate through a crystal structure. In classical physics, vibrations behave like sound waves, but at the quantum level, vibrations become particles called phonons. They’re created and absorbed as electrons push through the crystal lattice and distort the position of surrounding atoms. These distortions make the electrons appear heavier for a given momentum, the same way a person moves slower and feels heavier when attempting to run through water.
To determine if this phenomenon is responsible for the ALS experiment’s heavier-than-expected electrons, and narrowed bandwidth, the team turned to quantum mechanical calculations conducted at Berkeley Lab’s National Energy Research Scientific Computing Center (NERSC). There, they calculated the bandwidth and band dispersion of the carbon-60 monolayer using purely theoretical principles. They then compared the theoretical bandwidth, with and without electron-phonon effects, to the ALS-produced bandwidth, and got a nearly perfect match.
“It all falls together,” Louie says. “This experiment shows, at least for a monolayer on top of a metallic surface, that we don’t need additional phenomena like electron-electron interactions to explain the bandwidth. It also provides a quantitative understanding of the importance of electron-phonon interactions.”
The research is described in the Science paper, “Band Structure and Fermi Surface of Electron-Doped C60 Monolayers.” In addition to Louie, Berkeley Lab researchers Wan Li Yang and Zahid Hussain of the ALS, and Hyoungjoon Choi and Marvin Cohen of the Materials Sciences Division, contributed to the research. Other collaborators include Z. -X. Shen from Stanford University, and scientists from France’s Paris-Sud University, Italy’s Trieste Synchrotron, and Italy’s University Cattolica del Sacro Cuore.
Additional information
“Band structure and Fermi surface of electron-doped C60 monolayers,” by W. L. Yang, V. Brouet, X. J. Zhou, Hyoung J. Choi, Steven G. Louie, Marvin L. Cohen, S. A. Kellar, P. V. Bogdanov, A. Lanzara, A. Goldoni, F. Parmigiani, Z. Hussain, and Z.-X. Shen, Science, 11 April 2003
C60 Molecule Buckyball EDU2
Update on C60 fullerenes in olive oil
By Vince Giuliano and James P Watson
More than a year has passed since publication of the November 2012 blog entry Buckyballs, health and longevity – state of knowledge, It will be another year or two before we know whether researchers are capable of reproducing the extraordinary longevity impacts on rats reported in the 2011 publication The prolongation of the lifespan of rats by repeated oral administration of [60] fullerene. We don’t yet know a number of things we would love to know: 1. Whether indeed it is verified that “buttered buckyballs” can extend the lives of rats?, 2. if so, can they extend the healthspans and lives of humans?, and 3. exactly what molecular mechanisms would be involved in such lifespan extension?. Because rats normally live 2+ years, it will be at least another year before we start getting answers to the first question. Because we live 80+ years it may be decades before we start getting answers to the second question. But we can continue seriously discussing and speculating about the third question now, and that is the focus of this blog entry. In particular, a new mechanism is proposed for how C60 can possibly drastically reduce ROS and its pro-aging consequences.
Readers are referred to the earlier blog entry for in-depth background. Although there have been no further publications empirically relating C60 fullerenes (“buckyballs”) to mammalian longevity, several relevant research publications have appeared since. Some of these are reviewed here along with several relevant topics not previously well-covered.
1. C60 might significantly reduce reactive oxygen species produced by leaky mitochondria and associated cell damage, but not by a direct antioxidant effect.
In our minds, this is probably the central new finding. We have written previously about how “old” and “tired” mitochondria produce damaging ROS(ref)(ref), the Warburg effect and a negative cycle of activities that can lead to cancer. An important recent paper by David Sinclair and his associates describes how such ROS can be induced by age-related absence of sufficient NAD+ in the cell nucleus leading to a state of pseudohypoxia and insufficient expression of mitochondrially-coded protective genes(ref). DNA damage triggers the DNA damage response (ddr) which in turn triggers p53 activation which can then inhibit PGC-1b, resulting in the inhibition of gene transcription for nuclear-encoded mitochondrial proteins. Thus, this mechanism can induce high mitochondrial ROS generation, Warburg-type metabolism, increased oxidative stress leading to further negative effects such as more DNA damage. DNA damage can then lead to PARP-1 activation, which then can deplete nuclear NAD+, which then will stop SIRT1, SIRT6, and SIRT7 function. This then leads to a pseudohypoxic state of the nucleus due to HIF-1a stabilization. This in turn leads to inadequate TFAM, which then results in inadequate expression of mitochondrially-encoded proteins for electron transport. Thus, mitochondrial dysfunction can be triggered by telomere-dependent, DDR-mediated activation of p53.
It has previously been speculated that C60 buckyballs penetrate the cell and mitochondrial membranes and exercise an antioxidant ROS-quenching effect upon arriving within the mitochondria. C60 acts as a radical “sponge.”(ref) This may well be the case, but the cytoprotective effect of the EVOO buckyballs against carbon tetrachloride reported in the 2011 rat longevity study appears to be extraordinary for a simple antioxidant. Another very interesting hypothesis has been suggested in 2013. That hypothesis is that C60 serves to drastically reduce the production of the superoxide radical via reducing the electric potential across mitochondrial membranes. .Instead of cleaning up a dangerous superoxide radical via an antioxidant, this mechanism, would serve to prevent creation of that radical in the first place.
The argument is laid out in the 2013 publication Possible Mechanisms of Fullerene C60 Antioxidant Action. “Novel mechanism of antioxidant activity of buckminsterfullerene C60 based on protons absorbing and mild uncoupling of mitochondrial respiration and phosphorylation was postulated. In the present study we confirm this hypothesis using computer modeling based on Density Functional Theory. Fullerene’s geroprotective activity is sufficiently higher than those of the most powerful reactive oxygen species scavengers. We propose here that C60 has an ability to acquire positive charge by absorbing inside several protons and this complex could penetrate into mitochondria. Such a process allows for mild uncoupling of respiration and phosphorylation. This, in turn, leads to the decrease in ROS production.”
According to the 2013 publication Feasibility of the C60 Fullerene Antioxidant Properties: Study with Density Functional Theory Computer Modeling: “Fullerene C60 compound was recently found to be a potent anti-oxidant, which may be envisioned as a result of alteration of the inner mitohondria membrane electric potential with protons transport boosted by fullerenes. Here we briefly report on the theoretical test of the very possibility of protons to pass through the surface of C60 fullerene to become confined within latter thus possibly decreasing the transmembrane electric field gradient when fullerene crosses the mitochondria membrane. Quantumchemical calculations within Density Functional Theory are employed as a means of checking described scenario.” — “Fullerene C60 may be a powerful antioxidant demonstrating anti-aging activity. Recently Baati et al. showed that fullerene prolonged rat’s life span approximately twice [1]. Besides, rats treated with fullerene C60 demonstrated high resistance to carbon tetrachloride capable of triggering generation of huge amounts of harmful reactive oxygen species. Consequently, fullerene C60 was proposed to have high antioxidant activity in vivo. Geroprotective activity of C60 fullerene found experimentally in [1] is much higher than those of the most powerful reactive oxygen species scavengers. Reactive oxygen species may cause oxidative damage. Geroprotective activity of C60 fullerene found experimentally in [1] is much higher than those of the most powerful reactive oxygen species scavengers.”
As I understand it, the process goes like this:
1. The outer mitochondrial membrane is charged positively and the inner membrane is charged negatively. This is because free electrons are spun off in the complexes in the electron transfer chain. As the chain becomes less efficient and there is decline in expression of mitochondrial antioxidants, the more there is a charge differential. “Accumulation of Skulachev ions in the mitochondria is based on the transmembrane potential difference generated as a result of electron transport chain activity. The outer side of inner membrane of mitochondria has positive charge and the inner side has negative charge.” The actions of the electron transport chain involve four complexes, and you can get a fair idea how they work by viewing one of these animations.
2. Superoxide is created as a result of the cross-membrane charge differential, the amount being a nonlinear function of the differential. “The specific feature attributable to the generation of ROS by mitochondria is related to the fact that the higher is the membrane potential (the larger is the difference in the concentration of protons inside and outside the mitochondria), the higher is the level of the superoxide anion production. As it was shown [29], there is steep dependence of mitochondrial superoxide-anion-radical generation on transmembrane potential (Δ). Even a small (10–15%) decline of Δ resulted in tenfold lowering of ROS production rate.”
3. In the case of C60, the modeling studies suggest that the fullerenes are initially electrically neutral and penetrate easily to the center of the mitochondrial membranes. “Wong-Ekkabut et al. showed using molecular dynamics simulations [20] that C60 fullerene is capable of penetrating into membrane and accumulates in the middle of lipid bilayer.”
4. There, a fullerene may pick up as many as six protons, according to the quantum wave-function model.
5. The electrical gradient then sucks the positively charged fullerene across the inner mitochondrial membrane into the interior of the mitochondria. “DFT simulations allowed us to propose the following mechanism. C60 fullerene molecules enter the space between inner and outer membranes of mitochondria, where the excess of protons has been formed by diffusion. In this compartment fullerenes are loaded with protons and acquire positive charge distributed over their surface. Such “charge-loaded’’ particles can be transferred through the inner membrane of the mitochondria due to the potential difference generated by the inner membrane, using electrochemical mechanism described in detail by Skulachev et al. [18,24]. In this case the transmembrane potential is reduced, which in turn significantly reduces the intensity of superoxide anion-radical production.”
6. Once a positively charged fullerene is inside the mitochondria, the charge differential between the inner and the outer membrane is automatically reduced.
7. A net result is that a relatively small reduction in the charge differential can essentially turn down or turn off the production of superoxide.
8. This mechanism is completely independent of any antioxidant properties of the fullerene itself. Basically, the superoxide production is reduced through the C60 being in the role of a charge transporter.
9. If the fullerene has an antioxidant property once inside the mitochondria, that is an additional mechanism for reduction of ROS.
We note that a similar mechanism of action may explain the effectiveness of MitoQ which is commonly called a “mitochondrial antioxidant.” MitoQ is designed to be a molecule having a powerful positive charge, consisting of the cation triphenylphosphonium (TPP) covalently bonded to coenzyme Q-10. The result is a positively charged molecule. It is thought that the charge is sufficient to propel the molecule through the mitochondrial membrane into the interior of the mitochondria. Once inside a mitochondrion, as in the case of a C-60 fullerene, a MitoQ molecule reduces the charge differential across the mitochondrial membrane. This again should result in reduction of superoxide production. If the Q-10 moiety has an antioxidant function on Complex 2, that too enhances the antioxidant impact.
Similarly, triphenylphosphonium has been used tp target nitroxide radicals to mitochondria to protect against radiation exposure(ref).
So, C60 and MitoQ “antioxidants” don’t have to be antioxidants to work! If these models are correct, healthily-functioning mitochondria would automatically import less of C60 or MitoQ than mitochondria with leaky electron transport chains because the charge attraction would be less.
On first blush, the mechanism just described can possibly explain what seems to be a strange phenomenon observed in the famed rat study. EVOO far outlasts the period of supplementation. In the chronic C60 toxicity study that was done just to evaluate the “toxic” effects of C60 fullerenes, the C60 fullerenes in olive oil were initially administered every day at a dose of 4mg/kg body weight. However, after 7 days, the dose was reduced to weekly for the next two months. After that, doses were only given once every two weeks until the first rat died. Then no more C60 fullerenes were given. This amounted to 17 months of C60 fullerene treatment, then no C60 was administered for the rest of the rat’s lives. The rats who received C60 fullerene in olive oil lived as long as 66 months, which was 90% longer than the control group, which lived 14-38 months. Thus the C60 fullerenes had a prolonged effect that lasted for years after the last dose of C60 fullerenes was given. membrane waiting to come to its rescue and, because of its health due to control of ROS, be relatively long lasting.
This is a very nice conjecture except for one quite serious difficulty – which is that the half lives of rat mitochondria themselves are very short – up to a few weeks at most(ref). So, the explanation would only work if either the fullerenes convey extraordinary longevity to mitochondria or if fullerenes in the membrane of a mitochondrion undergoing mitophagy are recycled into new mitochondria.
2. There appears to be continuing concern that C60 may induce DNA/RNA damage and other forms of damage
This continues to be an important point though it was initially covered in the earlier blog entry.
The 2012 Publication A large-scale association study for nanoparticle C60 uncovers mechanisms of nanotoxicity disrupting the native conformations of DNA/RNA was quoted on in the previous post as was the 2005 report C60 binds to and deforms nucleotides. These are among several studies of C60 biological impacts based on theoretical modeling. I think what actually goes on in-vivo in the case of both studies is unknown. Nonetheless, such studies point to possible serious long-term negative consequence of C60 supplementation.
An additional 2009 study looked for evidence of damage to DNA as a result of oral consumption of C60, Oxidatively damaged DNA in rats exposed by oral gavage to C60 fullerenes and single-walled carbon nanotubes. “— BACKGROUND: C60 fullerenes and single-walled carbon nanotubes (SWCNT) are projected to be used in medicine and consumer products with potential human exposure. The hazardous effects of these particles are expected to involve oxidative stress with generation of oxidatively damaged DNA that might be the initiating event in the development of cancer. — OBJECTIVE: In this study we investigated the effect of a single oral administration of C60 fullerenes and SWCNT. METHODS: We measured the level of oxidative damage to DNA as the premutagenic 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in the colon mucosa, liver, and lung of rats after intragastric administration of pristine C60 fullerenes or SWCNT (0.064 or 0.64 mg/kg body weight) suspended in saline solution or corn oil. We investigated the regulation of DNA repair systems toward 8-oxodG in liver and lung tissue. RESULTS: Both doses of SWCNT increased the levels of 8-oxodG in liver and lung. Administration of C60 fullerenes increased the hepatic level of 8-oxodG, whereas only the high dose generated 8-oxodG in the lung. We detected no effects on 8-oxodG in colon mucosa. Suspension of particles in saline solution or corn oil yielded a similar extent of genotoxicity, whereas corn oil per se generated more genotoxicity than the particles. Although there was increased mRNA expression of 8-oxoguanine DNA glycosylase in the liver of C60 fullerene-treated rats, we found no significant increase in repair activity. CONCLUSIONS: Oral exposure to low doses of C60 fullerenes and SWCNT is associated with elevated levels of 8-oxodG in the liver and lung, which is likely to be caused by a direct genotoxic ability rather than an inhibition of the DNA repair system.”
Yet-another 2011 study only mentioned previously suggests that Non-liposomal (aka non-olive oil encapsulated) C60 fullerenes appear to be toxic and produce damage. It is In Vitro and In Vivo Genotoxicity Induced by Fullerene (C60) and Kaolin. “Nanomaterials are being utilized for many kinds of industrial products, and the assessment of genotoxicity and safety of nanomaterials is therefore of concern. In the present study, we examined the genotoxic effects of fullerene (C60) and kaolin using in vitro and in vivo genotoxicity systems. Both nanomaterials significantly induced micronuclei and enhanced frequency of sister chromatid exchange (SCE) in cultured mammalian cells. When ICR mice were intratracheally instilled with these nanomaterials, DNA damage of the lungs increased significantly that of the vehicle control. Formation of DNA adducts in the lungs of mice exposed to nanomaterials were also analyzed by stable isotope dilution LC-MS/MS. 8-Oxodeoxyguanosine and other lipid peroxide related adducts were increased by 2- to 5-fold in the nanomaterial-exposed mice. Moreover, multiple (four consecutive doses of 0.2 mg per animal per week) instillations of C60 or kaolin, increased gpt mutant frequencies in the lungs of gpt delta transgenic mice. As the result of mutation spectrum analysis, G:C to C:G transversions were commonly increased in the lungs of mice exposed to both nanomaterials. In addition, G:C to A:T was increased in kaolin-exposed mice. In immunohistochemical analysis, many regions of the lungs that stained positively for nitrotyrosine (NT) were observed in mice exposed to nanomaterials. From these observations, it is suggested that oxidative stress and inflammatory responses are probably involved in the genotoxicity induced by C60 and kaolin.”
Note that unlike the previously mentioned studies of potential damage, this study involved biological observations.
Studies have also looked at other forms of potential physiologic damage that might be induced by C60. The newer 2013 publication Human serum albumin interactions with C60 fullerene studied by spectroscopy, small-angle neutron scattering, and molecular dynamics simulations reports: “Concern about the toxicity of engineered nanoparticles, such as the prototypical nanomaterial C60 fullerene, continues to grow. While, evidence continues to mount that C60 and its derivatives may pose health hazards, the specific molecular interactions of these particles with biological macromolecules require further investigation. In this article, we report combined experimental and theoretical studies on the interaction of one of the most prevalent proteins in the human body, human serum albumin (HSA), with C60 in an aqueous environment. The C60–HSA interaction was probed by circular dichroism (CD) spectroscopy, small-angle neutron scattering (SANS), and atomistic molecular dynamics (MD) simulations to understand C60-driven changes in the structure of HSA in solution. The CD spectroscopy demonstrates that the secondary structure of the protein decreases in α-helical content in response to the presence of C60 (0.68 nm in diameter). Similarly, C60 produces subtle changes in the solution conformation of HSA (an 8.0 nm × 3.8 nm protein), as evidenced by the SANS data and MD simulations, but the data do not indicate that C60 changes the oligomerization state of the protein, such as by inducing aggregation. The results demonstrate that the interaction is not highly disruptive to the protein in a manner that would prevent it from performing its physiological function.”
3. Liposomal encapsulated C60 fullerenes are not toxic and have an anti-cancer effect, whereas non-encapsulated C60 fullerenes do NOT have an anti-cancer effect.
Going back to 2009, the publication Biological safety of liposome-fullerene consisting of hydrogenated lecithin, glycine soja sterols, and fullerene-C60 upon photocytotoxicity and bacterial reverse mutagenicity reported: “Various water-soluble derivatives of fullerene-C60 (C60) have been developed as detoxifiers for reactive oxygen species (ROS), whereas C60 incorporated in liposome (Lpsm) has not been reported yet. We prepared the liposome-fullerene (0.2% aqueous phase, Lpsm-Flln) which was composed of hydrogenated lecithin, glycine soja (soybean) sterols, and C60 in the weight ratio of 89.7:10:0.3, then examined the photocytotoxicity and bacterial reverse mutagenicity, as comparing with the Lpsm containing no C60. Photocytoxicity of Lpsm-Flln or Lpsm was examined using Balb/3T3 fibroblastic cells at graded doses of 0.49-1000 microg/mL under the condition of UVA- or sham-irradiation. The cells were irradiated with UVA (5 J/cm2, 320-400 nm, lambda max = 360 nm) at room temperature for 50 min. The resultant cell viability (% of control) did not decrease dose-dependently to 50% or less regardless of the UVA-irradiation. These results show that Lpsm-Flln or Lpsm does not possess photocytotoxicity to Balb/3T3 fibroblasts, and Lpsm-Flln may not exert a UVA-catalytic ROS-increasing action. A possibility for the reverse mutation by Lpsm-Flln or Lpsm was examined on four histidine-demanding strains of Salmonella typhimurium and a tryptophan-demanding strain of Escherichia coli. As for the dosages of Lpsm-Flln or Lpsm (313-5000 microg/plate), the dose-dependency of the number of reverse mutation colonies of each strain did not show a twice or more difference versus the negative control regardless of the metabolic activation, and, in contrast, marked differences for five positive controls (sodium azide, N-ethyl-N’-nitro-N-nitrosoguanidine, 2-nitrofluorene, 9-aminoacridine, and 2-aminoanthracene). The growth inhibition of bacterial strains and the deposition of Lpsm-Flln or Lpsm were not found. As a result, the bacterial reverse mutagenicity of Lpsm-Flln or Lpsm was judged to be negative under the conditions of this test. Thus, Lpsm-Flln and Lpsm may not give any significant biological toxic effects, such as photocytotoxicity and bacterial reverse mutagenicity.”
Another interesting article related to this point is the 2011 publication Anticancer Effects of Fullerene [C60] Included in Polyethylene Glycol Combined With Visible Light Irradiation Through ROS Generation and DNA Fragmentation on Fibrosarcoma Cells With Scarce Cytotoxicity to Normal Fibroblasts . As you can see. the PEG C60 solution is really a “nano particle” or “lissome.” “Fullerene [C60] included in polyethylene glycol (PEG) at a composing ratio of 1:350 w/w was examined for anticancer effects upon photodynamic therapy (PDT). Human connective tissue-derived fibrosarcoma cells HT1080 were decreased for a viability of 50% or 30%, by 3-h administration with PEG-fullerene [C60] at 50 or 100 ppm fullerene [C60] equivalent, respectively, subsequent rinsing out and irradiation with visible light (400‐600 nm, 140 J/cm2:450-fold as intense as in average outdoor), whereas the same tissue type-derived normal fibroblastic cells DUMS16 retained a viability of 93% or 85% under the same conditions. Anticancer effects were dependent on PEG-fullerene [C60] concentrations and irradiation doses, and scarcely exerted by PEG-fullerene [C60] alone, irradiation alone, or by fullerene [C60]-free PEG combined with irradiation, suggesting that the active principle may be fullerene [C60] as small as 0.0028 wt% versus the whole compound. Irradiation with PEG-fullerene [C60] occurred in intracellular DNA fragmentation according to TUNEL assay, and produced reactive oxygen species (ROS) such as hydroperoxides and peroxyl radicals or superoxide anion radicals in HT1080 cells as demonstrated by CDCFH-DA assay or nitroblue tetrazolium assay, respectively. Thus, PEG-fullerene [C60] is expected to be applied to anticancer PDT with scarce side effects on normal cells.”
4. One of the primary ways in which C60-EVOO may exercise its longevity effects on rats may be via promotion of autophagy in cancer cells, killing them.
This pathway was briefly discussed in the earlier blog entry on buckyballs and longevity. Cancer is normally a primary cause of death in rats. Cancer cells have evolved numerous mechanisms to resist cell death via apoptosis. They are subject to death via another set of mechanisms, however, mechanisms associated with autophagy. See the this list of previous blog entries related to autophagy, in particular the 2013 blog entry Autophagy – the housekeeper in every cell that fights aging. “Autophagy (“self eating”) is an old, evolutionarily conserved stress response that is present in all living cells. Like apoptosis, autophagy is a programmed response and has several sub-pathways. Unlike apoptosis, autophagy promotes life rather than death. Recent discoveries have shown that almost every genetic, dietary, and pharmacologic manipulation proven to extend lifespan activates autophagy as part of its mechanism of action. — Autophagy is the way your cells “clean house” and “recycle the trash”. Along with the ubiquitin proteasome system, autophagy is one of the main methods that cells use to clear dysfunctional or misfolded proteins. Autophagy can clear any kind of trash: intracellular viruses, bacteria, damaged proteins, protein aggregates and subcellular organelles. Although autophagy has long been known to exist, only recently has there been a clear understanding of the genes and pathways related to it. This recent evidence suggests that the declining efficacy of autophagy may be a driver of many of the phenotypic phenomena of aging. This blog entry explores the “evidence for the autophagy theory of aging” and builds a strong case that defective autophagy is a central driver for age-related diseases and aging itself.”
Autophagy is increasingly being investigated as an anticancer therapy. The 2012 publication Autophagy as a target for cancer therapy: new developments reports: “Autophagy is an evolutionarily conserved lysosomal degradation pathway that eliminates cytosolic proteins, macromolecules, organelles, and protein aggregates. Activation of autophagy may function as a tumor suppressor by degrading defective organelles and other cellular components. However, this pathway may also be exploited by cancer cells to generate nutrients and energy during periods of starvation, hypoxia, and stress induced by chemotherapy. Therefore, induction of autophagy has emerged as a drug resistance mechanism that promotes cancer cell survival via self-digestion. Numerous preclinical studies have demonstrated that inhibition of autophagy enhances the activity of a broad array of anticancer agents. Thus, targeting autophagy may be a global anticancer strategy that may improve the efficacy of many standard of care agents. These results have led to multiple clinical trials to evaluate autophagy inhibition in combination with conventional chemotherapy. In this review, we summarize the anticancer agents that have been reported to modulate autophagy and discuss new developments in autophagy inhibition as an anticancer strategy.”
The 2013 report Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment highlights the importance of utilizing autophagy for getting around cancer resistance to chemotherapies. “Induction of cell death and inhibition of cell survival are the main principles of cancer therapy. Resistance to chemotherapeutic agents is a major problem in oncology, which limits the effectiveness of anticancer drugs. A variety of factors contribute to drug resistance, including host factors, specific genetic or epigenetic alterations in the cancer cells and so on. Although various mechanisms by which cancer cells become resistant to anticancer drugs in the microenvironment have been well elucidated, how to circumvent this resistance to improve anticancer efficacy remains to be defined. Autophagy, an important homeostatic cellular recycling mechanism, is now emerging as a crucial player in response to metabolic and therapeutic stresses, which attempts to maintain/restore metabolic homeostasis through the catabolic lysis of excessive or unnecessary proteins and injured or aged organelles. Recently, several studies have shown that autophagy constitutes a potential target for cancer therapy and the induction of autophagy in response to therapeutics can be viewed as having a prodeath or a prosurvival role, which contributes to the anticancer efficacy of these drugs as well as drug resistance. Thus, understanding the novel function of autophagy may allow us to develop a promising therapeutic strategy to enhance the effects of chemotherapy and improve clinical outcomes in the treatment of cancer patients.”
You can also see these publications relating autophagy, cancer and survival. Cell death and autophagy: cytokines, drugs, and nutritional factors (2008), Autophagy: Can it become a potential therapeutic target?(2010), To die or not to die: that is the autophagic question(2008), Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer(2010),
The actions of autophagy in cancer can be either pro-oncogenic or anti-oncogenic in a context-dependent manner. Cancer cells may utilize autophagy-related pathways for their survival. Some of the complexities involved are described in the recent publications:
• Survival or death: disequilibrating the oncogenic and tumor suppressive autophagy in cancer (2013),
• The autophagic paradox in cancer therapy(2012), Ambra1 at the crossroad between autophagy and cell death (2013),
• Autophagy in tumorigenesis and cancer therapy: Dr. Jekyll or Mr. Hyde (2012)?
Getting back to the central issue here, for some time, it has been known that water-based C60 solutions have a capability to kill cancer cells via induction of autophagy.
This capability was briefly discussed in the earlier blog entry, mainly in the context of using C60 preparations in conjunction with cancer chemotherapy. One publication with abstract there is Autophagy-mediated chemosensitization in cancer cells by fullerene C60 nanocrystal (2009). Another publication mentioned there was Pristine C 60 Fullerenes Inhibit The Rate Of Tumor Growth And Metastasis (2011).
We recall that in the experiment where C60-EVOO extended the lifespan of rats by 90%, a remarkable observation was that none of the treated rats had developed any cancers.
A newer (2013) hypothesis is that induction of autophagy may be a generic property of many nanomaterials. What appears to be involved is activation of one or more stress pathways.
The 2013 publication Nanomaterials and autophagy: new insights in cancer treatment reports: “Autophagy represents a cell’s response to stress. It is an evolutionarily conserved process with diversified roles. Indeed, it controls intracellular homeostasis by degradation and/or recycling intracellular metabolic material, supplies energy, provides nutrients, eliminates cytotoxic materials and damaged proteins and organelles. Moreover, autophagy is involved in several diseases. Recent evidences support a relationship between several classes of nanomaterials and autophagy perturbation, both induction and blockade, in many biological models. In fact, the autophagic mechanism represents a common cellular response to nanomaterials. On the other hand, the dynamic nature of autophagy in cancer biology is an intriguing approach for cancer therapeutics, since during tumour development and therapy, autophagy has been reported to trigger both an early cell survival and a late cell death. The use of nanomaterials in cancer treatment to deliver chemotherapeutic drugs and target tumours is well known. Recently, autophagy modulation mediated by nanomaterials has become an appealing notion in nanomedicine therapeutics, since it can be exploited as adjuvant in chemotherapy or in the development of cancer vaccines or as a potential anti-cancer agent. Herein, we summarize the effects of nanomaterials on autophagic processes in cancer, also considering the therapeutic outcome of synergism between nanomaterials and autophagy to improve existing cancer therapies.”
5. The autophagy-inducing properties of C60 may also be useful for treating neurodegenerative diseases like Alzheimer’s Disease where accumulation of beta amloid plays a major role.
The 2011 publication C60 fullerene-pentoxifylline dyad nanoparticles enhance autophagy to avoid cytotoxic effects caused by the β-amyloid peptide reports: “Many studies have focused on the neuroprotective effects of C(60) fullerene-derived nanomaterials. The peculiar structure of C(60) fullerene, which is capable of “adding” multiple radicals per molecule, serves as a “radical sponge,” and it can be an effective antioxidant by reducing cytotoxic effects caused by intracellular oxidative stress. In this study, PEG-C(60)-3, a C(60) fullerene derivative incorporating poly(ethylene glycol), and its pentoxifylline-bearing hybrid (PTX-C(60)-2) were investigated against β-amyloid (Aβ)(25-35)-induced toxicity toward Neuro-2A cells. PEG-C(60)-3 and PTX-C(60)-2 significantly reduced Aβ(25-35)-induced cytotoxicity, with comparable activities in decreasing reactive oxygen species and maintaining the mitochondrial membrane potential. Aβ(25-35) treatment elicited adenosine monophosphate-activated protein kinase-associated autophagy. Cytoprotection by PEG-C(60)-3 and PTX-C(60)-2 was partially diminished by an autophagy inhibitor, indicating that the elicited autophagyand antioxidative activities protect cells from Aβ damage. PTX-C(60)-2 was more effective than PEG-C(60)-3 at enduring the induced autophagy. Our results offer new insights into therapeutic drug design using C(60) fullerene-PTX dyad nanoparticles against Aβ-associated diseases. —
FROM THE CLINICAL EDITOR: The neuroprotective effects of C60 fullerene-derived nanomaterials are known and thought to be related to their capacity of “absorbing” multiple free radicals. In this study, another interesting property is presented: they may enhance autophagy of beta-amyloid peptide, which could minimize the damaging effects of this peptide.”
While there appeared to be several research publications relating nano materials and C60 in particular to autophagy and the inhibitions of cancer, none of these publications deals explicitly with the C60-EVOO concoction used in the rat longevity experiments. Therefore it remains a conjecture that a major factor in the longevity of the rats was activation of autophagy pathways. As a conjecture, however, I believe it is a fairly good one.
6. There is a possibility that C60 fullerenes can be used to treat arthritis, mast cell and peripheral blood basophil-associated diseases.
From a patent application; Use of fullerenes for the treatment of mast cell and basophil-mediated disease (2006): “Mast cell (MC) and peripheral blood basophil (PBB)-associated diseases are treated or prevented, or their symptoms are alleviated by the administration of water soluble fullerenes (buckeyballs) to the individual under conditions sufficient to inhibit MC and PBB responses. MC and PBB responses are associated with, for example, various allergies including Type 1 hypersensitivity initiated by IgE-antigen, arthritis, multiple sclerosis, urticaria, atopic dermatitis, heart disease, etc. The treatment regimen can be enhanced using Chimeric fullerenes that specifically home to and inhibit MC and PBB cells. These molecules, for example, comprise fullerenes to which are attached IgE Fc or stem cell factor (SCF) peptides that bind to receptors specifically on MC and PBB cells. Additional molecules which may be used in the processes include IgE Fc or SCF peptides with several fullerenes covalently attached.” Also quoted in the earlier blog entry was the 2007 publication Fullerene nanomaterials inhibit the allergic response.
7. There is an increasing interest in liposomal C60 formulations
Item 3 above outlines what appear to be low-toxicity and high effectiveness advantages of liposomal C60 formulations. The 2013 publication Liposome Formulation of Fullerene-Based Molecular Diagnostic and Therapeutic Agents reports: “Fullerene medicine is a new but rapidly growing research subject. Fullerene has a number of desired structural, physical and chemical properties to be adapted for biological use including antioxidants, anti-aging, anti-inflammation, photodynamic therapy, drug delivery, and magnetic resonance imaging contrast agents. Chemical functionalization of fullerenes has led to several interesting compounds with very promising preclinical efficacy, pharmacokinetic and safety data. However, there is no clinical evaluation or human use except in fullerene-based cosmetic products for human skincare. This article summarizes recent advances in liposome formulation of fullerenes for the use in therapeutics and molecular imaging.”
8. Liposomal C60 fullerenes may protect against UVA skin damage
Again, it can be confusing but we think that these bucky balls may be both antioxidants and pro-oxidants.
The 2009 publication Fullerene-C60/liposome complex: Defensive effects against UVA-induced damages in skin structure, nucleus and collagen type I/IV fibrils, and the permeability into human skin tissue reports: “We previously reported biological safety of fullerene-C60 (C60) incorporated in liposome consisting of hydrogenated lecithin and glycine soja sterol, as Liposome-Fullerene (0.5% aqueous phase; a particle size, 76nm; Lpsm-Flln), and its cytoprotective activity against UVA. In the present study, Lpsm-Flln was administered on the surface of three-dimensional human skin tissue model, rinsed out before each UVA-irradiation at 4 J/cm(2), and thereafter added again, followed by 19-cycle-repetition for 4 days (sum: 76 J/cm(2)). UVA-caused corneum scaling and disruption of epidermis layer were detected by scanning electron microscopy. Breakdown of collagen type I/IV, DNA strand cleavage and pycnosis/karyorrhexis were observed in vertical cross-sections of UVA-irradiated skin models visualized with fluorescent immunostain or Hoechst 33342 stain. These skin damages were scarcely repressed by liposome alone, but appreciably repressed by Lpsm-Flln of 250 ppm, containing 0.75 ppm of C60-equivalent to a 1/3300-weight amount vs. the whole liposome. Upon administration with Lpsm-Flln [16.7 microM (12 ppm): C60-equivalent] on human abdomen skin biopsies mounted in Franz diffusion cells, C60 permeated after 24h into the epidermis at 1.86 nmol/g tissue (1.34 ppm), corresponding to 0.3% of the applied amount and a 9.0-fold dilution rate, but C60 was not detected in the dermis by HPLC, suggesting no necessity for considering a toxicity of C60 due to systemic circulation via dermal veins. Thus Lpsm-Flln has a potential to be safely utilized as a cosmetic anti-oxidative ingredient for UVA-protection.”
9. Hydroxylated C60 fullerences protect against radiation injury
The 2009 article The polyhydroxylated fullerene derivative C60(OH)24 protects mice from ionizing-radiation-induced immune and mitochondrial dysfunction reports: “These results suggest that the polyhydroxylated fullerene derivative C60(OH)24 protects against ionizing-radiation-induced mortality, possibly by enhancing immune function, decreasing oxidative damage and improving mitochondrial function.”
10. C60 fullerenes can generate ROS in the presence of UV light and induce bacterial killing as well as kill cancer cells
They do this via the generation of radicals directly and by inhibiting anti-oxidant enzymes, such as glutathione reductase, glutathione peroxidase, glutathione s transferase, catalase, and superoxide dismutase. Thus, c60 fullerenes are actually “ROS generators” The 2011 publication Photodynamic therapy with fullerenes in vivo: reality or a dream? relates: “The fullerene molecule with its unique structure of 60 carbon atoms arranged in a soccer ball structure is a molecule of great potential for a variety of applications and has drawn the attention of lots of physicists, chemists and engineers. Recently these nanostructures have also been studied for their biological activities with a view towards using them for biomedical applications. One of the therapies for which fullerenes may have a medical application is the light-based therapy called photodynamic therapy (PDT) [1], which is a nonsurgical, minimally invasive approach that has been used in the treatment of solid tumors and many nonmalignant diseases [2]. PDT is a nonthermal photochemical reaction, which requires the simultaneous presence of a photosensitizing drug (photosensitizer [PS]), oxygen and visible light (Figure 1). It is a two-step procedure that involves the administration of a PS, followed by activation of the drug with the appropriate wavelength of light [3–5]. The photoactivation of the drug generates singlet oxygen and other reactive oxygen species (ROS), which cause a lethal oxidative stress and membrane damage in the treated cells and in the case of tumors, leads to cell death by direct cytotoxicity and a dramatic antivascular action that impairs blood supply to the area of light exposure [6]. It is known that depending on the parameters involved, in vitro PDT can kill cancer cells via apoptosis, necrosis or autophagy. The direct killing effect of PDT on malignant cancer cells that has been studied in detail in vitro also clearly applies in vivo, but in addition, two separate in vivo mechanisms leading to PDT-mediated tumor destruction have been described. They are the vascular shutdown effect mentioned above [7], and the PDT-induced activation of the host immune system [8]. In case of antimicrobial PDT Gram-positive bacteria are found to be more susceptible as compared with Gram-negative bacteria. This observation is explained by the difference in the structure of their cell walls (Figure 2) [9]. In this vein, the earlier blog entry quotes from the 2012 publication Water-Dispersible Fullerene Aggregates as a Targeted Anticancer Prodrug with both Chemo- and Photodynamic Therapeutic Actions.
Image and legend source “Jablonski diagram – Initial absorption of a photon (or two photons of twice the energy) by the ground state of the singlet fullerene, which gives rise to the short-lived excited singlet state. This can lose energy by fluorescence (negligible in the case of fullerenes), internal conversion to heat or by intersystem crossing to the long-lived triplet state. Fullerene triplet states are efficiently quenched by molecular oxygen (a triplet state) to give type II (singlet oxygen) and type I (superoxide and hydroxyl radical) reactive oxygen species. In the absence of oxygen fullerene triplet states lose energy by phosphorescence.”
11. Fullerenes are receiving increasing attention for their medical therapeutic potentials
From the 2013 publication Application of fullerenes in nanomedicine: an update: “Fullerenes are carbon spheres presently being pursued globally for a wide range of applications in nanomedicine. These molecules have unique electronic properties that make them attractive candidates for diagnostic, therapeutic and theranostic applications. Herein, the latest research is discussed on developing fullerene-based therapeutics as antioxidants for inflammatory diseases, their potential as antiviral/bacterial agents, utility as a drug delivery device and the promise of endohedral fullerenes as new MRI contrast agents. The recent discovery that certain fullerene derivatives can stabilize immune effector cells to prevent or inhibit the release of proinflammatory mediators makes them potential candidates for several diseases such as asthma, arthritis and multiple sclerosis. Gadolinium-containing endohedral fullerenes are being pursued as diagnostic MRI contrast agents for several diseases. Finally, a new class of fullerene-based theranostics has been developed, which combine therapeutic and diagnostic capabilities to specifically detect and kill cancer cells.”
The 2010 publication Fullerenes as unique nanopharmaceuticals for disease treatment reports “As unique nanoparticles, fullerenes have attracted much attention due to their unparalleled physical, chemical and biological properties. Various functionalized fullerenes with -OH, -NH2, -COOH, and peptide modifications were developed. It summarized the biological activities of fullerenes derivatives in cancer therapy with high efficiency and low toxicity, as reactive oxygen species scavenger and lipid peroxidation inhibitor, to inhibit human immunodeficiency virus and to suppress bacteria and microbial at low concentration. In addition, the mechanism for fullerene to enter cells and biodistribution of fullerene in vivo was also discussed. This research focuses on the current understanding of fullerenes-based nanomaterials in the potential clinical application as well as biological mechanism of fullerenes and its derivatives in disease therapy.”
The proposed mechanism of action is the generation of ROS. See Molecular Docking Analysis of Fullerene (C60) with Human Antioxidant Enzymes: Implications in Inhibition of Enzymes (2013): “Fullerenes are a new class of carbon allotropes with unique physicochemical and biological properties for which they are widely used in biomedical technology. This leads to over exposure of fullerene and its detrimental effects on living organisms are not well characterized. Recent studies demonstrated that fullerene (C60) can generate free radicals that disrupt normal cellular function through lipid peroxidation and inducing cell death. It is not well understood whether fullerene induces the free radical generation by itself or the induction of oxidative stress is due to inhibition of enzymes associated with conversion of free radicals into water molecules. Hence forth, research is still evolving to understand the mechanism of fullerene toxicity on enzymes. In the present study we report the docking studies of fullerene with key antioxidant enzymes viz., glutathione reductase, glutathione peroxidase, glutathione s transferase, catalase and superoxide dismutase that scavenge free radicals. Docking was performed using Autodock 4.0 to examine the interactions of fullerene with all the five enzymes. Docking studies of fullerene with glutathione reductase, glutathione peroxidase, glutathione s transferase, catalase and superoxide dismutase demonstrated that it can bind with the active site residues of these enzymes through van der Waals interactions. Hence, we speculate that fullerene inhibit the activities of these enzymes with respective substrates which might lead to accumulation of reactive oxygen intermediates.”
See also Photosensitizers for targeted photodynamic therapy. a 2012 patent mentioned earlier.
In summary, C60 binds to the active sites of these enzymes via van der Waals interactions
12. Water soluble C60 fullerences can treat low back pain
This is amazing! See the 2013 publication A Novel Treatment of Neuroinflammation against Low Back Pain by Soluble Fullerol Nanoparticles. “Results: Fluorescence staining results indicated that TNF-α markedly increased the production of intracellular ROS and the number of apoptotic cells. Under fullerol treatment cellular apoptosis was reduced along with concomitant suppression of ROS. The expression of inflammatory cytokines IL-1 β, IL-6, COX-2, and PGE2, was also inhibited by fullerol in a dose-dependent manner. Furthermore, fullerol-treated cells exhibited up-regulation of anti-oxidative enzyme genes SOD2 and catalase. – Conclusion: The results obtained from this study clearly suggest that fullerol treatment suppresses the inflammatory responses of DRG and neurons, as well as cellular apoptosis by decreasing the level of ROS and potentially enhancing anti-oxidative enzyme gene expression. Therefore, fullerol has potential to serve as a novel therapeutic agent for low back pain treatment.”
Note that while several studies mentioned above suggest that fullerenes work to kill cancer cells and produce other beneficial effects by promoting ROS, that this and other studies suggest that fullerenes work to suppress inflammation by decreasing the expression of ROS. These seemingly contradictory conclusions require more detailed explanation since both of these observations could well be correct. For example, production of ROS could be a cellular response to C60, and above we related how C60 might suppress the generation of ROS by inhibiting the formation of superoxide as well as by antioxidant effects.
The 2013 publication Fullerol nanoparticles suppress inflammatory response and adipogenesis of vertebral bone marrow stromal cells-a potential novel treatment for intervertebral disc degeneration reports: PURPOSE: To investigate the potential of a free radical scavenger, fullerol nanoparticles, to prevent vertebral bone marrow lesion and prevent disc degeneration by inhibiting inflammation and adipogenic differentiation of vertebral bone marrow stromal cells (vBMSCs). STUDY DESIGN/SETTING: Fullerol nanoparticle solutions were prepared to test their in vitro suppression effects on mouse vBMSC inflammation and adipogenic differentiation compared with non-fullerol-treated groups. METHODS: With or without fullerol treatment, vBMSCs from Swiss Webster mice were incubated with 10 ng/mL interleukin-1 β (IL-1 β). The intracellular reactive oxygen species (ROS) were measured with fluorescence staining and flow cytometry. In addition, vBMSCs were cultured with adipogenic medium (AM) with or without fullerol. Gene and protein expressions were evaluated by real-time polymerase chain reaction and histologic methods. RESULTS: Fluorescence staining and flow cytometry results showed that IL-1 β markedly increased intracellular ROS level, which could be prevented by fullerol administration. Fullerol also decreased the basal ROS level to 77%. Cellular production of matrix metalloproteinase (MMP)-1, 3, and 13 and tumor necrosis factor alpha (TNF-α) induced by IL-1 β was suppressed by fullerol treatment. Furthermore, adipogenic differentiation of the vBMSCs was retarded markedly by fullerol as revealed by less lipid droplets in the fullerol treatment group compared with the adipogenic group. The expression of adipogenic genes PPARγ and aP2 was highly elevated with AM but decreased on fullerol administration. CONCLUSIONS: These results suggest that fullerol prevents the catabolic activity of vBMSCs under inflammatory stimulus by decreasing the level of ROS, MMPs, and TNF-α. Also, fat formation in vBMSCs is prevented by fullerol nanoparticles, and, therefore, fullerol may warrant further in vivo investigation as an effective biological therapy for disc degeneration.
13. Water soluble C60 fullerenes up regulate the production of SOD2 and catalase
Again, see the 2013 publication A Novel Treatment of Neuroinflammation against Low Back Pain by Soluble Fullerol Nanoparticles. Also again, this is getting more and more confusing, but it makes sense if you read the above and following article and the one in #14:
Fullerene nanoparticles and their anti-oxidative effects: a comparison to other radioprotective agents (2012) “Radiation therapy occupies an important position in the treatment of malignant diseases in spite of the existence of radiation side effects on normal tissues. Thus, substances are being developed which are designed to reduce both the acute and long term radiation effects on healthy tissues. Currently a sulphur-containing compound amifostine (WR2721, ethyol) is used in clinical practice as a radioprotectant. However, it itself has considerable side effects including hypotension (found in 62% of patients), hypocalcaemia, diarrhoea, nausea, and vomiting. Carbon nanospheres, known as fullerenes, and their water soluble derivatives (e.g. C60(OH)24, dendrofullerene DF-1) exert anti-oxidative properties and reduce damage to the DNA in irradiated cells. Water soluble fullerenes are low-toxic substances and thus, are attractive in terms of their use as radioprotectants.”
Again, we seem to have contradictory findings between this and other reports: fullerenes induce ROS and oxidative stress and fullerenes protect against oxidation, fullerenes reduce DNA damage and fullerenes induce DNA damage, water-soluble fullerenes have low toxicity and water soluble fullerenes have potentially high toxicity. Again, attention has to be paid to the nature of the study involved (e.g. quantum effect modeling study vs. cell-level biochemical effects study vs observation study of impact on oxidative stress parameters on rats), the particular kind of fullerene involved (e.g. water soluble vs lipid encased, etc.), and exact experimental conditions. The devil is in the details.
14. Liposomal (aka olive oil encapsulated) C60 Fullerenes may make a key difference in animal health, but figuring out how may require thinking “out of the box.”
As indicated above, the famed rat longevity study could be in complete concordance with what both of us believe about stress, stress signaling, and the difference between “good ROS” (signaling ROS within a hormetic dose and duration range) and “bad ROS” (damage-inducing ROS, of dose or duration outside of the hormetic range), and about non-antioxidant mechanisms that drastically diminish ROS. Here is yet-another factor (Jim) has learned:
By complexing with catalase, C60-EVOO fullerenes PRODUCE hydrogen peroxide and singlet oxygen, but inhibit the hydroxyl radical production. Thus, they quench “bad ROS damage” but produce “good ROS signaling.” See:
• Detection of Hydrogen Peroxide and Glucose Based on Immobilized Detection of Hydrogen Peroxide and Glucose Based on Immobilized C60-Catalase Enzyme
• Oxidatively Damaged DNA in Rats Exposed by Oral Gavage to C60 Fullerenes and Single-Walled Carbon Nanotubes (2009)
• Comparative Photoactivity and Antibacterial Properties of C60 Fullerenes and Titanium Dioxide Nanoparticles (2008)
• Photodynamic therapy with fullerenes in vivo: reality or a dream? (2011).
There is probably much more to be told to complete the C60 health story. We will continue to follow it.
About Vince Giuliano
Being a follower, connoisseur, and interpreter of longevity research is my latest career. I have been at this part-time for well over a decade, and in 2007 this became my mainline activity. In earlier reincarnations of my career. I was founding dean of a graduate school and a university professor at the State University of New York, a senior consultant working in a variety of fields at Arthur D. Little, Inc., Chief Scientist and C00 of Mirror Systems, a software company, and an international Internet consultant. I got off the ground with one of the earliest PhD’s from Harvard in a field later to become known as computer science. Because there was no academic field of computer science at the time, to get through I had to qualify myself in hard sciences, so my studies focused heavily on quantum physics. In various ways I contributed to the Computer Revolution starting in the 1950s and the Internet Revolution starting in the late 1980s. I am now engaged in doing the same for The Longevity Revolution. I have published something like 200 books and papers as well as over 430 substantive.entries in this blog, and have enjoyed various periods of notoriety. If you do a Google search on Vincent E. Giuliano, most if not all of the entries on the first few pages that come up will be ones relating to me. I have a general writings site at www.vincegiuliano.com and an extensive site of my art at www.giulianoart.com. Please note that I have recently changed my mailbox to vegiuliano@agingsciences.com .
Source: http://www.anti-agingfirewalls.com/2014/02/25/update-on-c60-fullerenes-in-olive-oil/
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