635 replies to this topic

[tintinet]

Possible effect: wound healing and "hardiness"? And, perhaps, clutzyness ?

Over the past two days I've sustained a couple of unintentional minor self-inflicted injuries with relatively minimal discomfort and relatively (ISTM) quick minor abrasion and bruise healing. It's hard to be sure about such things, but the outcomes of these incidents have pleasantly surprised me.

[Metrodorus]

Rats have an average lifespan. There are always those that live a number of standard deviations from the mean,
No experimental explanation is needed. There is no need to go looking for errors. Max lifetime of a Wistar rat is, for males 3.2 years. (38 months), and for females 3.8 years (44 months). However, every stain of Wistar rat varies in its theoretical maximum lifespan.


http://books.google....PA312&lpg=PA312

I think it is reasonable to accept that there are no methodological errors in this experiment in terms of its implementation - and that we can be more confident now, given the additional scrutiny this paper has had, due to the errors in the supporting visuals. The paper and the submitted supporting evidence was gone over with a fine toothcomb, and it was accepted.

The only error was a software glitch in producing a graph that was not picked up until publication, and a slide substitution that was not particularly significant. The underlying data was not affected.

We need to look for the mechanism of lifespan extension elsewhere that arose from from that moderate olive oil intervention.

[niner]

That one Olive Oil only rat sure sticks out - the one that lived 50 months. Perhaps an error or cross contamination of food?

Actually I wasn't going to say it but I speculated the same....looks suspiciously like it might have somehow got a dose of the C60 either by mistake or contamination.

Considering that it wasn't one olive oil rat, but in fact TWO of them that lived 50 months, that is a head-turning result. Statistical artifact? The odds against that strike me as small. Still, it's been a couple days since anyone pointed out the N=6 issue, so... Whoomp! There it is. When N=6, two rats are thirty thee percent of the cohort. The olive oil result, without even considering the C60, is simply amazing. If this paper were published with no reference at all to C60, it would have created quite a stir here, and we'd all be seeking out Tunisian olive oil and drinking enormous quantities of it. Gosh Dang, I wish someone would hurry up and replicate this with a decent N in a good rat facility. I don't think I want to wait til 2017 for the paper to come out, though.

[JohnD60]

That one Olive Oil only rat sure sticks out - the one that lived 50 months. Perhaps an error or cross contamination of food?

Actually I wasn't going to say it but I speculated the same....looks suspiciously like it might have somehow got a dose of the C60 either by mistake or contamination.

I am not familiar with how rats are segregated in tests like this, is it possible that one or more of the c60 rats vomited up some of the c60, and it was eaten by a couple of the hungry OO rats?

[Metrodorus]

Quoted from the paper:
The estimated median lifespan (EML) for the C60-treated rats was 42
months while the EMLs for control rats and olive oil-treated rats
were 22 and 26 months, respectively. These are increases of 18 and
90% for the olive-oil and C60-treated rats, respectively, as compared
to controls.
The log-rank test leads to c2 values (one degree of freedom) of
7.009, 11.302, and 10.454, when we compare water-treated and
olive oil-treated rats, water-treated and C60-treated rats, and olive
oil-treated and C60-treated rats, respectively. This means that olive
oil extends the lifespan of rats with respect to water with a probability
of 0.99 while C60-olive oil extends the lifespan of C60-treated
rats with a probability of 0.999 and 0.995 with respect towater and
olive oil treatments, respectively.

[foolish trends]

Here is the full discussion of the Baati corrigenda in retraction watch>

The most important sentence, as far as this thread is concerned,is that the review panel accepted that the errors in the graph and the histology slide made no material difference to the conclusion reached.
"Due consideration has been given to the potential effect of these errors on the overall results and conclusions drawn, and so it has been decided the conclusions are still valid. The authors have provided explanations of how the errors were made during the preparation of graphics and images."

Looking at the original survival graph, the source of error is immediate - the connecting lines between the data points after each death should have been vertical, but they were sloped, adding extra weeks to the overall duration of the study. The relative positions of the data points to one another was not, however, affected by this error.

All the fullerene OO rats were still alive after all the other rats were dead, irrespective of the graph you look at. What is striking about this study, is the uniformity of survival of the fullerene OO cohort, that striking horizontal line at the top of the graph.


http://retractionwat...lems/#more-8407

And clearly they still completely messed up the lifespan graph. If the average lifespan of the Olive Oil rats is 28 moths why does the new graph show that none of the Olive Oil rats were dead at 28 months?
Extremely sloppy would be a compliment at this point. I find it quite impossible that the person in charge of this study could carefully treat rats on a protocol for 4 years but can't interpret his intern's graphs
like a grandfather that can't use a computer.

[niner]

If the average lifespan of the Olive Oil rats is 28 moths why does the new graph show that none of the Olive Oil rats were dead at 28 months?

Baati says:

The estimated median lifespan (EML) for the C60-treated rats was 42
months while the EMLs for control rats and olive oil-treated rats
were 22 and 26 months, respectively.

So it appears to be even worse than you thought. I don't know why the EML is so nonsensical, but I find it a little hard to believe that they made an error of that magnitude and no one caught it, given the amount of attention this paper has had. It probably has something to do with the definition and assumptions behind the non-parametric Kaplan-Meier estimator.

It makes no sense to me. Can anyone explain why these so-called "medians" are so much at odds with the data as plotted?

[buckwheats]

the x axis of that graph starts at '10'. if you subtract that from the oo rat lifespans and average them you get

23+24+26+27+40 = 140 --> 140/5 = 28.

with a median of 26.

wait, were there 5 oo rats or 6?. I can't tell if two died at 50 months (seems unlikely) or if they just messed up the vertical line drops. i guess it wouldn't change the median really, just the average.

Edited by buckwheats, 10 July 2012 - 05:25 PM.

[niner]

the x axis of that graph starts at '10'. if you subtract that from the oo rat lifespans and average them you get

23+24+26+27+40 = 140 --> 140/5 = 28.

with a median of 26.

wait, were there 5 oo rats or 6?. I can't tell if two died at 50 months (seems unlikely) or if they just messed up the vertical line drops. i guess it wouldn't change the median really, just the average.

That would only be the case if they were talking about "length of experiment" or some such thing. They're talking about the actual age at which the rats died, so it wouldn't be right to subtract 10. There were six rats. Two died in the last week, which is why the vertical bar at that point is twice as long as the others. The number they are calculating is not a simple median, so it's ok that it doesn't exactly match the simple median taken off the graph. If you calculate % life extension using the simple medians, it isn't wildly different than what they get with the Kaplan-Meier EML. The simple median and the EML, on the other hand, are too divergent for comfort. I am obviously missing something about the calculation. I'd like to think that if N were high enough, those medians would converge, but it's not obvious that it would work that way.

[buckwheats]

ah, i see. it seems most probable that it's the median/mean estimates that are just weird due to the small amount of data and questionable statistical procedures, not the graph that is wrong.

i am not too familiar with maximum likelihood estimates, but my understanding is you are maximizing the parameters of some model (in this case parameters of a survivorship function) so that the model best explains the data. but given how grouped together the deaths of the c60 rats are, it does not seem unreasonable that the type of model that is typically used for rats might not be the best one for these c60-fed rats.

like if you tried to fit the data to a convex survivorship function when it really should be concave, then the median of the survivorship function might be underestimated and seem out of line with the data.

Edited by buckwheats, 10 July 2012 - 07:47 PM.

[niner]

Would you argue that the added strength is comparable to steroids, which can suppress the immune system? I bring this up in light of Japanese researchers learning that the protein C1q is responsible for aging -- and that suppressing C1q suppresses the immune system and improves longevity. See: Scientists discover protein responsible of ageing in Japan

Some have reported that the effect is similar to steroids, but it's highly unlikely that the mechanism would be the same, since they are very different chemically. I'm not sure if anabolic steroids have the same immunosuppressive effects as some corticosteroids or not, but my guess is not. The article on C1q sounds rather profoundly hyped. I don't think there is any way that a single protein could be called "responsible [for] aging". That makes it sound like the sole cause. Maybe it's related in some minor way.

[foolish trends]

Would you argue that the added strength is comparable to steroids, which can suppress the immune system? I bring this up in light of Japanese researchers learning that the protein C1q is responsible for aging -- and that suppressing C1q suppresses the immune system and improves longevity. See: Scientists discover protein responsible of ageing in Japan

Some have reported that the effect is similar to steroids, but it's highly unlikely that the mechanism would be the same, since they are very different chemically. I'm not sure if anabolic steroids have the same immunosuppressive effects as some corticosteroids or not, but my guess is not. The article on C1q sounds rather profoundly hyped. I don't think there is any way that a single protein could be called "responsible [for] aging". That makes it sound like the sole cause. Maybe it's related in some minor way.

Corticosteroids are great for inflammation and do a lot of bad things. Anabolic steroids are quite different. Taking straight Test(osterone) will suppress the production functions in the testes but the rise in testosterone in the body does great things for strength, libido, mood, etc. AIDS patients were prescribed HGH and Deca-durabolin(a steroid well known in athletics for recovery/tissue repair) as standard fair. That is until the US goverment passed RAW deal for the Chinese Olympics arbitrarily banning sports enhancing substances. Then many people who needed Deca woke up one day and weren't allowed to refill their prescriptions.

There are also many steroid derivatives that focus on specifics like maximum weight gain or higher metabolism allowing someone to get extremely low body fat without losing lean weight...these tend to come with side effects, most of which, to my understanding, has to do with whether it is more anabolic(growth) or androgenic(viril) and the body changing estrogen levels and such to keep ratios in check, but I digress. The point being that anabolic steroids are not the same suppressive daemon that cortisol steroids are.

Edited by foolish trends, 11 July 2012 - 11:08 PM.

[Rob Wegner]

Corticosteroids are great for inflammation and do a lot of bad things. Anabolic steroids are quite different. Taking straight Test(osterone) will suppress the production functions in the testes but the rise in testosterone in the body does great things for strength, libido, mood, etc. AIDS patients were prescribed HGH and Deca-durabolin(a steroid well known in athletics for recovery/tissue repair) as standard fair. That is until the US goverment passed RAW deal for the Chinese Olympics arbitrarily banning sports enhancing substances. Then many people who needed Deca woke up one day and weren't allowed to refill their prescriptions.

There are also many steroid derivatives that focus on specifics like maximum weight gain or higher metabolism allowing someone to get extremely low body fat without losing lean weight...these tend to come with side effects, most of which, to my understanding, has to do with whether it is more anabolic(growth) or androgenic(viril) and the body changing estrogen levels and such to keep ratios in check, but I digress. The point being that anabolic steroids are not the same suppressive daemon that cortisol steroids are.

Corticosteroids v. Anabolic steroids, makes perfect sense. Thanks!

I am still curious about the relationship between C60oo and the immune system?

Edited by Rob Wegner, 12 July 2012 - 01:37 AM.

[treonsverdery]

Googletarian thought of it first

Its interesting how C60 treated rats all die in very small time frame, when compared to other groups. Hayflick limit?

I think they could take various human tissue lines at 1, 3 , 7 ,10 hayflick divisions remaining then see if buckminsterfullerene notably ncreased the longevity pf the human tissue types. They could publish meaningful human data at less than 2 months of observing the near limit cytes living longer.

There is even the possibility of transplanting 1, 3, 7, 10 hayflick division remaining cytes to a living animal, then feeding it oil, oil with buckminsterfullerene, as well as regular food to see if metabolites or body responsive cytokines were actually causing the effect

[treonsverdery]

Googletarian thought of it first

Googletarian on 21 April 2012 said
how C60 small time frame, to other groups. When compared with Hayflick limats all die in very it?



I think they could take various human tissue lines at 1, 3 , 7 ,10 hayflick divisions remaining then see if buckminsterfullerene notably ncreased the longevity pf the human tissue types. They could publish meaningful human data at less than 2 months of observing the near limit cytes living longer.

There is even the possibility of transplanting 1, 3, 7, 10 hayflick division remaining cytes to a living animal, then feeding it oil, oil with buckminsterfullerene, as well as regular food to see if metabolites or body responsive cytokines were actually causing the effect

Edited by treonsverdery, 12 July 2012 - 09:30 PM.

[eternaltraveler]

http://www.plosmedic...al.pmed.0020124

[maxwatt]

http://www.plosmedic...al.pmed.0020124

All research studies are false, including this one. ???

[AdamI]

http://www.plosmedic...al.pmed.0020124

All research studies are false, including this one. ???

Research studies in the medical field, and research studies in general are very different.
Just as the study says people are bias. Soo if a socialist is going to make a study on the benefits of Obamacare vs some other type of medical program. The study will most likely be very faulty
.
That is what that study has shown, it is not applicable on medical studies. Don't you agree?
It also uses the word false, not say outright lying. Which it would be with medical studies. Just twisting the truth to suit your own needs. I guess the green houseeffect is a good example,where scientist that needs to prove that the green house effect truely do exist have discarded many works that have proven the other case that there is no green house effect and that earths temperture movies in cycles.
For exemple Greenland infact was green when vikings discovered it, and they could farm. Then the vikings moved away after 1-200 years because of worsening wheather, soo they couldn't farm

[johnross47]

http://www.plosmedic...al.pmed.0020124

All research studies are false, including this one. ???

Research studies in the medical field, and research studies in general are very different.
Just as the study says people are bias. Soo if a socialist is going to make a study on the benefits of Obamacare vs some other type of medical program. The study will most likely be very faulty
.
That is what that study has shown, it is not applicable on medical studies. Don't you agree?
It also uses the word false, not say outright lying. Which it would be with medical studies. Just twisting the truth to suit your own needs. I guess the green houseeffect is a good example,where scientist that needs to prove that the green house effect truely do exist have discarded many works that have proven the other case that there is no green house effect and that earths temperture movies in cycles.
For exemple Greenland infact was green when vikings discovered it, and they could farm. Then the vikings moved away after 1-200 years because of worsening wheather, soo they couldn't farm

Maybe some clever scientist could invent a pill that makes reality obvious.Obamacare is only socialist if your are so far out to the right that you've lost sight of your own body. Compared to any European system it is not even vaguely socialised.
As for climate warming denial; if you fall for that mountain of bullshit you probably need to change your reading matter. The climate graphs produced by the climate change scientist you are libelling all show the medieval warm period in the northern western hemisphere. They also show it was colder in some other locations, and drier. The data misused by the denialists is mostly sourced from climate science and then abused. Try doing a few hours reading on Real Climate. A very good site with clear explanations of all sorts of aspects of climate science and detailed analysis of all the arguments and supposed controversy.

[d4shing]

Please keep it on topic.

[Rob Wegner]

Please keep it on topic.

I agree. Longevity science must remain free from politics and religion.

Edited by Rob Wegner, 14 July 2012 - 10:23 AM.

[Mind]

http://www.plosmedic...al.pmed.0020124

All research studies are false, including this one. ???

Of course not. The point is that bias exists and is more prevalent than most recognize. Also, the smaller the study, the more likely it will turn out to be false, or non-repeatable. The Baati study is TINY, TINY, TINY, so we should be particularly on guard for mistakes.

As far as bias goes, I would think this study is less likely to be affected, because they were looking for toxicity and wound up finding life extension. So it was a surprise.

[Metrodorus]

Longevity science must be free of politics and religion.

On this one can not but agree - however, longevity research, should it lead to effective life span lengthening, will have have important political implications.

The Baati study is not the first to show lifespan extension in a mammal for fullerene. Water soluble fullerene adducts have also shown this effect in mice. This, I think, is grounds for increased confidence in the Baati study.

[niner]

http://www.plosmedic...al.pmed.0020124

All research studies are false, including this one. ???

This paper lists a number of characteristics of the kind of study that's wrong, and Baati really only has one of them; a small sample size. Probably the most important of the characteristics is small effect size, and in the case of Baati, the effect is gigantic. Because the effect is so large, the odds that it happened due to random chance, even with the small n, is miniscule. While that doesn't mean that a non-random error couldn't exist, it does counteract the usual problem of small sample sizes. The fact that lifespan extension has been seen in I think five different species with various fullerene analogs lends credence to the result.

If you read the comments on this paper at plosmed, you'll see a number of criticisms of the methodology. The paper has a provocative title, and the media had a field day with it, but it has some significant problems itself, and frankly, I think it's misleading. Healthy skepticism is good, but knee-jerk skepticism shouldn't be confused with intellectual rigor.

[maxwatt]

There is I suppose a small but non-zero chance that the cohort of mice Baati used for the study had a genetic quirk leading to exceptionally long life with such interventions as OO and C60. Not that I actually believe that as an explanation, but neither can I eliminate it.

[Metrodorus]

Max - this is virtually impossible - the wistar rats (not mice,note) used in lab experiments are genetically homogenous to a high degree. That is the whole point of using a specific type, specially bred for experiments - to reduce this variable to a negligible level.

The chance of all the rats taking OO fullerene having a quirk is so vanishingly remote as to be not worth considering.

Edited by Metrodorus, 14 July 2012 - 01:59 PM.

[niner]

Max - this is virtually impossible - the wistar rats (not mice,note) used in lab experiments are genetically homogenous to a high degree. That is the whole point of using a specific type, specially bred for experiments - to reduce this variable to a negligible level.

The chance of all the rats taking OO fullerene having a quirk is so vanishingly remote as to be not worth considering.

I think what maxwatt might have meant is that ALL Wistar rats have such a quirk engendering amazing response to both C60 and olive oil, which while still extremely unlikely, at least isn't virtually impossible, like only the six in the C60 arm having a genetic abnormality would be. I'd really like to see C60-oo in some different species.

[FrankMH]

Would it be interesting to test VO2 Max? I was thinking about trying to reach a confirmed plateau taking the Multi Stage Fitness Test and then start dosing. I'm 29 and fitness for me is playing squash about 3 times a week. When I plateau, I think I'd have to log the gains I normally obtain from doing the test a few times first, and then dose.

[eternaltraveler]

Because the effect is so large, the odds that it happened due to random chance, even with the small n, is miniscule.

a couple animals in the olive oil alone group lived about the same length, and its a pretty big mistake to put much faith in any tiny study, especially one where there have already been some pretty large retractions made that should make a reasonable person question the whole thing even ignoring the fact that there are a million other things where a tiny study showed an increase in rodent lifespan that did not pan out. At this point there is absolutely no justification for the present level of hype here. The fact that a bunch of people are intentionally ingesting this stuff at this point is completely insane.

if you want to do something reasonable. Do a mouse study or something. Use a couple groups of 20. Doing this without controls would be worse than worthless. The cost of this should be measured in hundreds of dollars to 1000(starting with middle aged animals will be a little more expensive, they cost about 20 bucks a piece, whereas young animals are practically free because you only need 2 and a couple months latter you have infinite). I'd be happy to assist with a reasonable experimental design as well as give advice on how a rodent study can cost 100s of times less than universities tell you they cost. Of course all of that requires someone to be willing to actually do work.

[niner]

Because the effect is so large, the odds that it happened due to random chance, even with the small n, is miniscule.

a couple animals in the olive oil alone group lived about the same length, and its a pretty big mistake to put much faith in any tiny study, especially one where there have already been some pretty large retractions made that should make a reasonable person question the whole thing even ignoring the fact that there are a million other things where a tiny study showed an increase in rodent lifespan that did not pan out. At this point there is absolutely no justification for the present level of hype here. The fact that a bunch of people are intentionally ingesting this stuff at this point is completely insane.

if you want to do something reasonable. Do a mouse study or something. Use a couple groups of 20. Doing this without controls would be worse than worthless. The cost of this should be measured in hundreds of dollars to 1000(starting with middle aged animals will be a little more expensive, they cost about 20 bucks a piece, whereas young animals are practically free because you only need 2 and a couple months latter you have infinite). I'd be happy to assist with a reasonable experimental design as well as give advice on how a rodent study can cost 100s of times less than universities tell you they cost. Of course all of that requires someone to be willing to actually do work.

This study is profoundly in need of replication, I agree. A systematic error is entirely possible. Of course, a systematic error wouldn't be ruled out by having more animals; that would just make the already good P's even better. However, a second study, even if small, would be unlikely to experience an identical systematic error. The 90% increase in EML over controls is, as far as I know, greater than any intervention ever reported in a rodent that didn't involve genetic modification. The profound squareness of the mortality curve is interesting. All this just points to the need for replication, but I can't blame people for being exited.

The olive oil arm of the study really hasn't had the attention it deserves- again, another result in need of replication. A recent paper using a large Spanish cohort of the EPIC study looked at risk of mortality as a function of olive oil consumption, and saw a distinct (and substantial) dose response. We've been talking about getting a mouse study together. AgeVivo is feeding C60-oo to his three pet mice at home, but a larger controlled study is needed. It doesn't seem like it would need to cost all that much, but it would take a committed person to run it.