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April 18, 2012
Buckyballs Prolong Life? Really?
I'm really, really not sure what to make of this paper (PDF). It's from a team that was studying the long-term toxicology of C60 (fullerene, "buckyballs") by giving them to rats as a solution in olive oil. The control groups were water and olive oil without C60. The compound has already been shown to have no noticeable short-term toxic effects, so they probably didn't expect anything dramatic in the lower-dose long-term mode.
Wrong. What they found was that the fullerene/olive oil group had their life spans extended by some 90%, which would make this mixture perhaps the most efficacious life-extended treatment ever seen in a rodent model. This is a very odd and interesting result.
There's nothing bizarre about the pharmacokinetics, anyway. A reasonable amount of the C60 is absorbed after an oral dose (they did both oral gavage and intraperitoneal dosing), with a time course consistent with the very high lipophilicity of the compound. Distribution is still being worked out, but a lot of any given dose ends up in the liver and spleen (although it doesn't accumulate with successive q.d. dosing), with detectable amounts even crossing the blood-brain barrier. It has a long half life, consistent with enterohepatic recirculation and elimination through the bile (no C60 was found in the urine).
The most likely mechanism for the life-extension effects is through oxidative stress and free radical scavenging. There have been several reports of C60 as an antioxidant, although there have also been reports that it can be cytotoxic via lipid peroxidation. (One difference was that that report was with aggregates of C60 in water, versus soluble C60 in oil, but there are other reports that hydrated C60 does the opposite: there's clearly a lot that hasn't been cleared up here). In this study, even at very low doses, C60 appears to protect rodents against carbon tetrachloride-induced liver damage, for example, which is known to involve a radical process. Significantly, it does so while showing protection against glutathione depletion, which also suggests that it's directly scavenging reactive intermediates.
These are reasonable (but unproven) hypotheses, and I very much look forward to seeing this work followed up to see some more light shed on them. The whole life-extension result needs to be confirmed as well, and in other species. I congratulate the authors of this work, though, for giving me the most number of raised eyebrows I've had while reading a scientific paper in quite some time.
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