Chronic Buckyball Administration Doubles Rat Lifespan | Hacker News Reader

Chronic Buckyball Administration Doubles Rat Lifespan

extremelongevity.net

81 pointsbcowcher45 comments

Article: http://extremelongevity.net/wp-content/uploads/C60-Fullerene...

The part getting the attention has to do with longevity; for that part of the article, data comes from "[t]hree groups of 6 rats".

This was a single experiment in which n=6 rats received the C60 ('buckyball') composition, n=6 received just the oil, and n=6 received water (which can cause adverse effects in rats). Interestingly, a protective effect of oil gavage in some rat strains has apparently been observed before ( http://www.ncbi.nlm.nih.gov/pubmed/3591539 ) but that's a bit of a distraction since the focus is on the C60.

All treatment stopped after a few months when the first control rat died. Given that the half life is 14h for peritoneal injection of this particular substance, there should have been nothing left of it after ~70h. How it continued to affect rat lifespan for several months afterward would require explanation.

Could be that it's a fluke given the small groups involved.

Not likely, since statistical tests were performed to ensure that the results seen were not due to random chance. The sample size they used is actually pretty large for studies like this.

However, the study is complicated since rats are sensitive to abdominal gavages and it tends to reduce their lifespan. Similarly, there are studies that show chronic administration of olive oil increases life span.

So you have a situation where one control (water only) leads to decreased lifespan and another control (vehicle - olive oil only) tends to increase lifespan. Neither of these are ideal controls since they are known to affect the rat.

That said, they did fancy stats and presumably accounted for this fact.

An n of six per arm in a three-arm study is not "actually pretty large."

It's just a single paper by a single lab, and probably a pretty small lab. This isn't Merck running a clinical trial.

No amount of fancy accounting can ever save someone from the fact that they performed one experiment one time with a treatment group of 6. Extraordinary claims require at least a replicated experiment.

Those tests for statistical significance aren't very strong in this case. It might be that the study in question only had a 5% chance of giving this result by chance, but given that this particular study was selected to our attention for news-worthiness the actual chance of it being a valid result are far less than 95%[1]. Also, a sizeable minority of published papers have statistical errors, even in good journals[2].

[1]http://xkcd.com/882/ [2]http://www.economist.com/node/2724226

You are right in general, but the study in question actually claims 99.9% significance, not 95%. That's pretty strong.

Ah, thank you for pointing that out. It changes things quite a bit.

That's exactly the message my summary intended to convey :-)

I find myself a little sceptical of articles on a website called "extreme longevity", to be honest...

... also, skimming the linked paper, the largest sample I see is "sixty rats randomly divided into 10 groups of 6 rats". I'm not sure if that's really large enough to draw any solid conclusions, and I don't see any P-values for the lifespan data -- but I freely admit I'm neither any kind of biologist nor a stats expert, so I may be talking rubbish.

Actually, that's one of the few reputable casual sites that cover the field of aging and longevity research, along with my own, Fight Aging!

Well, it was published in a real journal (Biomaterials) with an impact factor of 7.882. So the research is theoretically peer-reviewed and solid, in that the paper itself isn't just making things up.

So what might be going on here?

http://www.fightaging.org/archives/2012/04/a-puzzling-fuller...

The average life span of the Wistar rats used is 2-3 years (24 - 36 months). This was a small study size, but that's no so important in determining whether you have an actual means of life extension if you can show that any of your study group lived much longer than usual - but it is important when it comes to the degree of life extension. If the study group is small, as it is here, using only a handful of rats, then the size of the effect can be much more readily distorted by chance. This line in the paper jumped out at me: "Before C60 administration, the rats were fasted overnight but with access to water." If they failed to fast the control group, then we're looking at yet another study that failed to control for calorie restriction, and this is actually largely an intermittent fasting study - which has certainly been shown to extend life in rats.

This would explain how the olive oil administration also apparently extended life significantly...

This is not it. Fasting was done for pharmacokinetics study, not for chronic toxicity study. That two studies were separate is evident from the description, e.g. rats were acclimated for 7 days for pharmacokinetics study and 14 days for chronic toxicity study.

That is also a plausible reading of the paper. It doesn't look like they go into any great detail as to the protocol for administration in the longer term study.

I'm skeptical of significant antioxidant effects in vivo from a naturally occurring compound given that antioxidants in general haven't done much for longevity without being heavily designed substances (like SkQ1, for example). Simply flooding the body with antioxidants is usually slightly worse for longevity or a null effect - they don't get to the mitochondria where they might do some good.

More information from the authors would be good. All things considered, I'm sure we'll be hearing more on this in the years ahead; people will try to replicate it, the researchers will be grilled on their work, etc.

Be careful when looking at lifespan studies. A huge increase in lifespan vs. control does not mean much if the control is badly treated and short-lived compared to max lifespan for that rat strain. Some rats normally live to 42 months. The C60 could be making up for bad conditions without extending max lifespan. If so, many compounds have been shown to do this. This exact scenario was the cause of the resveratrol craze.

Well, given the title I was expecting to be snorting dismissively, but this actually does seem interesting and I hope there's followup work. In particular, the fact that this was a group investigating C60 toxicity makes me less immediately suspicious of fudging, but then again if their funding were coming from someone making something with C60 in it they might have subconsciously treated the C60 rats better.

What I'd really like to see is a duplication with a larger sample size and some sort of blind setup with the people caring for the rats. And even then, there are good reasons to expect that this won't carry over to humans, given that humans already live so long for an animal of our body size.

Interesting -- there are plenty of articles on fullerene administration to rats over the past 10 years [1], but no mention of longevity effects.

[1]: http://scholar.google.com/scholar?hl=en&q=fullerene+rats

I just took a look myself and it turns out that there is evidence: http://www.ncbi.nlm.nih.gov/pubmed/17079053.

The thing is, you can't patent fullerene so it will never ever make a great deal of money as a supplemental treatment, and so likely won't get that much attention.

Just discovered that google can convert long series of units.

Say you wanted to do this, at the obvious risk of some undiscovered toxicity, and say you weigh 200lbs.

At a cost of fullerene-c60 of $592 for 5 grams, at 1.7mg/kg, you're daily dose costs $18.26 http://www.google.com/?q=1.7mg%2Fkg+x+200lbs+x+592%2F5+dolla...

Even worse, however, is the olive oil you have to eat each day, with the C60 disolved into it is 39 teaspoons! http://www.google.com/?q=1.7+mg/kg+/+0.8+mg/ml+x+200+lbs+to+...

Which is 4/5ths of a cup of oil per day.

EDIT: I guess they didn't actually get a daily dose.

    we treated the rats daily only during 7 days and weekly 
    during the ﬁrst two months, then every two weeks until 
    one control rat died.

Nor did they get dosed their entire lives, as earlier in the paper, we find that

    After ﬁve months of treatment (M15) one rat treated with 
    water only exhibited some palpable tumours in the
    abdomen region. Due to the rapid development of tumours 
    (about 4 cm of diameter) this rat died at M17. As rats
    are known to be sensitive to gavages, we decided to stop 
    the treatment for all rats and to observe their
    behaviour and overall survival.

So, it looks like they only treated for 7 months, for the most part, once every two weeks, and then no further treatment. The treated rats, after only 7 months of treatment, achieved the benefit.

Human dosing is different than animal dosing. It doesn't translate straight mg/kg.

Obviously not everything studied in Rat models scales well or is even effective at all in Humans, but the potential applications of this will surely raise a few eyebrows!

Interesting to note a daily diet of olive oil increased their average lifespan by 4 months alone! The Omega-3 fatty acids in it at a guess... but I wonder what the exact methods of action are for C60!

If nothing else, I'm sure the thought of extending the life of their favourite pet would make a few rat owners happy!

"Buckminsterfullerene" is named after Buckminster Fuller, who popularized geodesic domes. He had a word commissioned for him, "Dymaxion", and he used it for lots of his projects: Dymaxion Map https://en.wikipedia.org/wiki/Dymaxion_map, Dymaxion House https://en.wikipedia.org/wiki/Dymaxion_house, Dymaxion Car https://en.wikipedia.org/wiki/Dymaxion_Car .

This doubles median lifespan, not absolute lifespan, it's still impressive but would be much more so if it was doubling max lifespan.

edit: Checked the data, interestingly there's a fairly wide range of death in the non-buckyball population (more than 1 year) but the buckyball population all died within 3 months, oddly enough none of the groups overlap, the data looks almost perfect. Will be interesting to see what the results are with more subjects.

Full Study: http://extremelongevity.net/wp-content/uploads/C60-Fullerene...

The median is more robust than the average, and the average that is more robust than the maximal or minimal.

* One strange case/rat can modify the maximal or minimal a lot (For example, some kill a rat with a gun or you are "lucky" and get a Methuselah rat.)

* A strange event also can modify the average a lot (If someone kill a rat immediately at the beginning of the experiment, the "new" average is approximately (n-1)/n times the "original" average.

* But some unusual problem doesn't modify the median too much. The median changes from the value of a rat to the value of the next/former rat, which is usually very close. But it doesn't matter how small or big the strange case is, the median is essentially fixed between two values, so it is difficult to modify too much.

The real problem is that 6 is a small number and it is difficult to get good statistical result with only 6 cases.

The study is not using median, it is using EML(estimated median lifespan), which is calculated by Kaplan-Meier estimator. This actually seems to be standard in lifespan studies.

http://en.wikipedia.org/wiki/Kaplan-Meier_estimator

When I read headline I thought of those buckyball desk toys. I thought playing with them would help me live longer.

Choose a random compound X, feed it to rats and see what happens. Could somebody explain how does one choose X?

Most likely "anyway that is able to obtain grant money."

Have they done this experiment with any other configurations of carbon?

But how much of that effect is explained by the olive oil?

They had a plain olive oil control that increased the lifespan from 22 to 26 months, compared to 42 with the C60 + oil.

but, it also sez the following : "They also demonstrated that the compound is fully absorbed via the GI tract and totally eliminated from the body in 10 hours." so, not sure what causes the increase in life-span. although, the cryptic "attenuation of age-associated increases in oxidative stress" does hint at something, probably the effect that this combo causes as it is moving through the GI tract ?

"qwe sdawrqre sdzaamik3432 mkl" -> that's cryptic.

This is not, it's simply a bit vague. If it attenuates age-associated increases in oxidative stress then it probably has an anti-oxidant effect. Alternatively, it affects the systems responsible age-related oxidation - in other words, an indirect anti-oxidant action.

There were three groups:

1. control (normal rats) - 22 month lifespan

2. olive oil rats - 26 month lifespan

3. olive oil + C60 rats - 42 month lifespan

So, only about 1/5th of the effect is explained by the olive oil.

at the risk of sounding strange, is this or anything similar available to buy anywhere?

It is being produced for research purposes, so I guess you could ask at your local university lab where they sourced it. But caution is in order: the experiment described in the article was intended to find out about the toxicity of BF C60. Given that many of its chemically-similar relatives are indeed highly toxic, it's probably not a good idea to ingest this stuff yet. Six rats don't prove this substance is harmless.

Just curious, what are it's chemically similar relatives? I'm no chemist, but I thought the only thing remotely similar to c60 is graphite (which is harmless).

Carbon nanostructures have been shown to embed themselves as fibres into tissues, causing irritation and possibly cancer. So even if buckyballs are themselves harmless, likely carbon contaminants from the production process might not be. The balls also have a tendency to encase small molecules within them, and then delivering those encased substances directly into the human cell. So special care would have to be taken that the buckies are really "empty". That's all under the assumption the C60s are themselves non-toxic.

Some fullerene compound substances are toxic, but the C60 pure fullerene seems to be OK so far. Still, I wouldn't bet my life on it. If, for example, the C60 bucky would have a toxicity mechanism comparable to carbon nanotubes, that may be damage unlikely to show up during the limited lifetime of a rat - but it may well be much more relevant to humans who live 30 times as long!

I wonder if this is found in any foods?

You're kidding, right?

Normal ash does contain some C60, but only in small quantities compared to the amount of horrible stuff-that-will-kill-you present.

This is one of the big problems with the supplement industry. The moment one small scale, unreplicated study shows potential for a compound people jump all over it regardless of the fact that it hasn't been shown to be safe in humans and the actual experiment hasn't been replicated.

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