How does C60 extend life?
Noone pretends to know why the "Bucky rats" in the C60 chronic toxicity study lived nearly twice as long as the control group. The study has such an astonishing result that it has even be suggested that a lab worker must have killed a few rats by mistake and replaced them with younger rats. But that can't be true, because all C60 rats lived extraordinary long lives, way beyond their maximum natural lifespan. It has also been suggested that someone deliberately sabotaged the study by replacing all rats with younger animals, but again, this seems highly unlikely. If we take the study at face value, then we have to accept that something very extraordinary has been discovered: Something that makes mammals live double their expected lifespan, in excellent health all the way until the theoretical maximum (Hayflick limit) of death due to old age.
Dr. Fathi Moussa, principal author of the C60 rat study, is not sure that the longevity effect is due to the "super-antioxidant" properties of C60, but it is his best guess. He remarks that C60 is unique in that it can go deep into the cells and cell walls:
Vidcaps taken October 26, 2012. Source: C60.net. No restrictions applied at that time (post #13).
Dr. Moussa has no commerical interest in C60 and holds no C60 patents or C60-related shares.
The study remarks how it is normal for Wistar rats to die of tumors or pneumonia, and how the C60-treated rats neither developed cancer nor lung problems - they simply died of general organ failure associated with old age - they reached their genetical maximum lifespan, so to speak. Whereas the rats in the control group - Wistar rats of the same age and genetically on a par with their C60 brethren, died of tumors and pneumonia. The researchers considered four possible explanations and thought it most likely that the C60's unparalleled antioxidant properties had something to do with it. However, there must be more to it than that, because the rats only received 24 doses - how can 24 days of C60 supplementation add years to their lives? C60 is eliminated from the body in 10 to 24 hours, at least that is what studies tell us. However, those studies have only looked at the general tissue distribution of C60, not at the mitochondrial cell membrane, to give but an example. The major theories how lipofullerenes' anti-aging effects are:
(1) C60 remains in the lipid bilayers of the cells and mitochondria, doing its ROS-neutralizing work for weeks or months.
Lipofullerenes could act as super-antioxidants on the cellular level, where they remain for a very long time, since they are not "used up" when they act as antioxidants, and they are constantly recycled in the cell.
(2) The C60 physically rejuvenates organisms on the cellular level, for example by DNA demethylation or by otherwise reversing cellular damage on the molecular level.
Interestingly, the size of the Buckyball C60 molecule is such that it fits exactly inside the "minor groove" DNA winding and it indeed binds to it, protecting it against Methyl groups that degrade and neutralize the DNA:
Here are some postulations made in the Longecity forum on how C60 may extend healthy life:
(3) "Attenuation of age-associated increases in oxidative stress."
(4) "I'm wondering if the fullerene might not be the active longevity ingredient. Maybe it's just the transport. And dissolving it in olive oil also allows some olive oil molecules to penetrate the fullerene sphere and get transported to places by the fullerene that orally ingested olive oil wouldn't make it to. Like deep into many cells throughout the body even those across the bbb. It that's right, all the longevity effects observed are just an amplification of the effects of the olive oil."
(5) "My guess is that it binds with toxins."
(6) "It is a catalytic radical scavenger - i.e. it is able to re-cycle and repeat its activity over and over. It accumulates in mitochondria. It has antiviral action. C60 has anti-cancer properties. Possibly, as with methylene blue, there might be a hormetic affect - with low dosages having a positive effect, and higher doses a deleterious one."
(7) "Maybe enhancing neurite growth sufficiently enhances feedback signaling in the body and that is what results in an enhanced immune response."
(8) "Since the mechanism of action is still unknown we have no idea if the buckyballs are destroyed in the process of performing whatever function they are performing. Maybe they somehow bust up AGEs and are destroyed in the process. Maybe they settle in and become a conduit for some biophotonic reaction."
(9) "We do know fullerene passes the blood brain barrier, and has neuroprotective effects."
(10) "C60 is a catalyst. It is not used up in the process of its action."
(11) "C60 is able to associate with mitochondria and induce a cytoprotective antioxidant effect."
(12) "C60 might be resetting the mitochondria to a younger age."
(13) "We humans have been cooking our food for a long time and the soot from these fires maybe contained fullerenes. Perhaps fullerenes are an important part of the paleolithic diet."
(14) Here's a sketchy hypotheses of how C60 might work:
- Fullerenes wrapped in oil are transported to mitochondria for burning.
- Once there, the oil is stripped and the naked fullerenes are attracted to other hydrophobic molecules, such as the methyl groups on the mitochondrial DNA, and reacts with them, stripping them from the DNA.
- Demethylation of the DNA thus reverses the epigenetic DNA changes that result in dysfunction of the mitochondria.
(15) There's been some mention of mitochondrial biogenesis in this thread... Is this something that fullerenes are known to do? Mitochodrial biogenesis means the creation of new mitochondria.
(16) Fullerenes are known to like methyl groups, and that they could steal them from DNA would certainly provide a tidy explanation of how this works.
(17) Fullerenes might exist in a more longer-lived reservoir, like in the membrane of a long-lived somatic cell.
(18) My hypothesis is that fullerenes wipes out the methylation, the DNA automatically recovers it, and the effective age is set to zero. The DNA will begin to age again, and a later treatment can reset it back to zero. Keep resetting every few years and the ultimate limit then passes to the telomeres and epigenetics of the nuclear DNA.
(19) It's very clear that C60 has mitochondrial activities; for example, animals treated with C60 are more resistant to radiation effects, and are far more resistant to the oxidative damage from carbon tetrachloride ingestion. That isn't just a reset to a youthful state, because youthful animals would be injured by both radiation and CCl4.
(20) Olive Oil is a 5-LO inhibitor. 5-LO inhibition reduces ROS, independent of P53. I cannot escape the conclusion that the choice of the Olive Oil solvent, per se, cannot be dismissed as being unimportant to the Buckyball study conclusion.
(21) I have a hypothesis: Because of its hydrophobic propensity, C60 incorporates itself into cell membranes thereby presenting the adducted olive oil which disrupts the signaling pathways of arachidonic acid in the phospholipids therein while also sopping up supersoxide everywhere the C60 finds it, nice "one-two". How/why does the C60 pass through the cytosol into the mitochondrial membranes? Wouldn't it want to stay in the cell membrane? Is it shunted through the cell membrane by a channel protein or an inner membrane channel protein? Is there a charge graident involved? Is it just possible that because it behaves like a wave also...it makes for the mitochondria and leaves the olive oil in the cell membrane?
(22) Harman, in this 2001 paper posits that fullerene may work in the mitochondria as a blocking agent. Many antioxidants,at therapeutic doses,actually decrease the efficiency of the mitochodria, which is why possibly we do not see increases in the maximum lifespan. If fullerene is indeed a blocking agent, then it acts by stopping oxygen from generating reactive oxygen species and superoxide formation, while having no negative impact on mitochondrial functionality. Other studies posit it is a superoxide dismutase mimetic.
(23) Drugs, diet, or exercise are all capable of changing gene expression; for example, resveratrol alters the expression level of on the order of 1000 genes. It's very likely that fullerenes change the expression level of numerous genes as well. For the vast majority of these genes, the changes in expression are transient, and when the drug is withdrawn, expression returns to normal. In some cases, however, there are apparently long-lasting changes put in place by CpG (de)methylation, histone (de)acetylation, etc. These are epigenetic modifications.
(24) ..the Fullerene Solvent served as the means for "guiding" the Fullerenes to the "cell type" that the solvent has a natural affinity for, to the appropriate "receptor" of that cell type..
(25) C60 is thought to be a "SOD Mimetic", SOD is an enzyme that clears out the destructive superoxide ROS in your cells.
(26) I suspect that the C60 that finds its way into non-mitochondrial membranes isn't hurting anything, and may be helping some, but the fraction that gets into mitochondrial membranes is what's doing the magic, because it's close to the source of damaging superoxide ions.
(27) I think that the conjugation of fullerene with molecules present in olive oil is crucial - and it makes no sense whatsoever to tinker with the basic formula when the knowledge of what is going on is basically non-existent. If you are going down this route, stick to olive oil.
(28) I wouldn't say that we don't have a clue how this works. I'd say there are some hints. We know it's redox active, and that fullerene carboxylic acid compounds can act as SOD mimetics, turning superoxide radical anion into oxygen and H2O2. We know that superoxide is generated in mitochondria, and it's at least reasonable to suspect that a fullerene fatty acid adduct could become part of the mitochondrial membrane.
(29) I don't think it is a stretch to assume that the positive effects of C60, if any, are tied to it's relative inertness.
(30) That it is the Olive Oil combination with C60s that extended life spans in the surprising way it did suggests that our innate Immune System driven CAIP is implicated in some way in the study result.
(31) A resetting of the Mitochondrial DNA in the gut related to our Innate Anti-Inflammatory mechanisms resets our ability to manage the auto-immune diseases (like cancer) which, increasingly, knock us off as we age.