526 replies to this topic

[Turnbuckle]

If Hines' estimate of 740-1000 days was based on the longest you might expect a petshop mouse to live, then two of AV's mice made it that far...

He doesn't say that. He says, "Most mice live 740 to 1,000 days."

You can shop around and try to find lower estimates for pet store mice, but in the end it's not a worthwhile exercise. And now I see someone else is doing a C60 experiment with 8 rats obtained from a hobby breeder, of unknown ages and not using any controls. And I'm sure people here will follow it and post hundreds of comments, but nothing whatsoever will be learned.

Edited by Turnbuckle, 03 August 2013 - 02:42 PM.

[YOLF]

Link to the other C60 Rat trial that TB mentioned:
http://www.longecity...ng-my-rats-c60/

I would like to see controls in this group though they have stated that as their beloved pets they won't be using controls.

[ambivalent]

With a small sample size I can see limited value of controls - especially if I had age and strain and am expecting exceptional results. I would prefer to use the resource to produce a larger sample of the experimental group or groups.

[hav]

With a small sample size I can see limited value of controls - especially if I had age and strain and am expecting exceptional results. I would prefer to use the resource to produce a larger sample of the experimental group or groups.

I have to agree with Turnbuckle in principle against considering this an n=2 study if any statistics about the group are going to be discussed. Although given that with n=3 and no controls, any statistics would have very little power to them anyway. I just think it would make us look bad tossing a non-favorable data point after the fact. Detracting from our general credibility.

The concept of after the fact data selection has its uses. I found it discussed in this interesting paper on Retrospective Power Analyses which mentions:

The importance of doing a power analysis before beginning a study (prospective power analysis) is universally accepted: such analyses help us to decide how many samples are required to have a good chance of getting unambiguous results. In contrast, the role of power analysis after the data are collected and analyzed (retrospective power analysis) is controversial, as is evidenced by the papers of Reed and Blaustein (1995) and Hayes and Steidl (1997). The controversy is over the use of information from the sample data in retrospective power calculations. As I will show, the type of information used has fundamental implications for the value of such analyses. I compare the approaches to calculating retrospective power, noting the strengths and weaknesses of each, and make general recommendations as to how and when retrospective power analyses should be conducted.

The problem here as I see it is that it could look like we're cherry picking our data to reach arbitrary conclusions.

But I could see the usefulness of tabulating subjects that die of cancer/tumors compared to those that don't. But you'd need some reference points to draw any conclusions. Without controls or at least a breed with known statistics, I don't see how that could be meaningful.

Howard

[niner]

The problem with statistics is that it has built-in assumptions about normal distributions and randomness. When you understand the data, it's no longer some sort of normally-distributed black box. I think that averaging the tumor case with the two normal cases is inappropriate because these data are not normally distributed- there are two different classes. There aren't enough data points to be treating them as some sort of gaussian distribution anyway. I mean, c'mon guys, there are only three mice. We'd better hope the ITP picks this up...

[AgeVivo]

We'd better hope the ITP picks this up...

and do something in *rats*, esp *similar* to baati et al if the ITP does not

[yuriythebest]

Just go to a mouse forum and ask if 2 out of 3 at 2.75 years is untypical.

you know what, that is a pretty neat idea - I did just that (I posed as the owner of said mice for convenience- I hope the author doesn't mind) to get a sampling of the general opinions:

http://www.miceareni...-question#33427

and

http://www.paw-talk....html#post649414

(I of course omitted any talk of "experiments" as this might be perceived negatively among the common pet mouse owner)

Edited by yuriythebest, 17 August 2013 - 07:49 PM.

[ambivalent]

Hi yuri,

well done for doing this - the initial feedback appears encouraging: none of the owners could do better than AVs two mice. Even with only those three owners as a sample, I would guess we are dealing with a collectively fairly large sample of mice. So Avs result stands up pretty well and exceptional. It's probably reasonable to guess at an average of a bit less than 2 years judging from their remarks.

@AV are you still anticipating undertaking a necropsy for your mice ?

Edited by ambivalent, 20 August 2013 - 07:09 PM.

[HHM]

Very interesting indeed�

[yuriythebest]

right, so to summarize:
1. The mice lived to a very nice long age (perhaps 90yrs in human years?)
2. The mice did NOT live a 2x max lifespan - that would be around 4-6 years

Edited by yuriythebest, 30 August 2013 - 10:19 PM.

[AgeVivo]

Hello,
it has been a long time since the 2 black dead mice have been in a freezer, I have made the necropsies this week, the one with a white belly had a soft spleen cancer with metastases and the one with a black belly had some hard mass/tumor in the heart and it seems had had in consequence a very high blood pressure before death. All in all, no regrets, those mice died from strong consequences, the experiment pushed them until the end, a different end for each of them.

I am putting the photos here: http://www.longecity...tober-9th-2012/
[To access you need to be a member (left panel, "Support Us">"Become a member") otherwise it will put an error]
Please do not put the pictures/text openly on the internet, as some people could be shocked by pictures of necropsies

Cheers.

[Turnbuckle]

So if all 3 mice had cancer, there is no longer any rationale for throwing out the first death (or even treating it as a control as some wanted to do). It has to be averaged in with the others.

[PWAIN]

The question for me is whether these mice might have lived a lot longer if they didn't have cancer. The point here being did the treatment retard the aging process but the cancer got in the way of the testing?

[Turnbuckle]

We have studied cancer incidence in mice as a function of age in those cohorts where the rodents are allowed to live very close to their full natural lifetime. We find that the incidence rises as a function of age, but then flattens and turns over at an age of about 800 days. This behaviour is similar to that which we observed (Pompei and Wilson, 2001) in the Surveillance, Epidemiology, and End Results (SEER) data where the age distribution of human cancer incidence turns over at about age 80. Although other fits are possible, the three-parameter beta function model fits both the mouse data and the human data well. The beta model implies, and the data do not deny, the interpretation that cancer is not a certainty and mice may also outlive their cancers, although high-dose cohort results suggest cancer might be certain if dose is sufficiently high. Limited data suggest that the cancer age distribution, including the turnover, may be time shifted by dietary restriction

Age distribution of cancer in mice: the incidence turnover at old age

[Kevnzworld]

So if all 3 mice had cancer, there is no longer any rationale for throwing out the first death (or even treating it as a control as some wanted to do). It has to be averaged in with the others.

We all feel differently about this. I don't believe that the first mouse was on C60 long enough to be factored in. It's cancer was probably pre existing and the supplementation of C60 would not have effected its lifespan.
It is troubling that the remaining two mice both developed cancer, even with somewhat extended lifespans.

[ambivalent]

Given the results, I'm inclined to agree with Turnbuckle. Had these mice not died of cancer I would have said it is proper to exclude the third mouse. But we now have 3 mice dying of cancer while being treated with c60: they should be grouped together (I feel). They all will have had some likelihood of being afflicted with cancer at the start of treatment - but with significantly varying of degrees of probability and stages of development. It is also clear that the experiment has been extremely useful - hitherto no rodents had died from cancer while receiving c60oo. Now we have an experiment with all rodents dying of cancer receiving treatment of c60, albeit from an older age. It remains possible that c60 slows the onset of cancer, is cancer preventive and it is highly probable it does not regress cancer even at an less advanced stages. In addition we've no data to inform on how long a non-cancer developing mouse treated with c60 at a late age might live, which offers up an optimism not present had they died from another age related disease. The experiments are quite distinct - we have c60 with (highly probable) huge life extension and cancer prevention in Baati when c60 is administered at an early stage and with AV's work we witness c60 offering no cancer prevention, but probable (lower confidence) moderate life-extension when c60 is administered at a late stage of life. The experiment has certainly informed on the effect of c60oo on rodents. Once again thanks for your efforts AV.

Edited by ambivalent, 15 November 2013 - 12:52 AM.

[Turnbuckle]

hitherto no rodents had died from cancer while receiving c60oo.

Is this true? I don't recall the Baati paper saying that. The indication was that livers were protected from administration of toxins, but as for the chronic toxicity study that had the C60 animals living longer, no cause of death was given for the C60 group.

[ambivalent]

hitherto no rodents had died from cancer while receiving c60oo.

Is this true? I don't recall the Baati paper saying that. The indication was that livers were protected from administration of toxins, but as for the chronic toxicity study that had the C60 animals living longer, no cause of death was given for the C60 group.

That was my understanding from what I've read on this forum on several occasions - I seem to recall this being a quote from Prof: Moussa (perhaps in the interview).

[niner]

with AV's work we witness c60 offering no cancer prevention, but probable (lower confidence) moderate life-extension when c60 is administered at a late stage of life.

I suppose that c60 offers no cancer prevention, if you define prevention in absolute terms. It may well have forestalled the development of cancer in the last two animals, though in the end it was not sufficient. Lacking controls and a larger population, we can only speculate here, but these are very valuable data points.

Because the first animal died so early, I'm comfortable considering it as an outlier, as it was almost certainly already sick at the start of the experiment. I know we don't all see this the same way, so we should probably just analyze the data both ways and report it as such.

[YOLF]

How are the other home trials going? I haven't seen much if anything posted about them.

[ambivalent]

It may well have forestalled the development of cancer in the last two animals, though in the end it was not sufficient.

I certainly agree. I was trying to imply this by suggesting it remains possible c60 delays the onset of cancer. Regarding the outlier, it feels right to include it (to me) but also take a view without it, as you suggest, because it naturally remains highly probable it had cancer from the outset but highly uncertain whether the other two did.

[ambivalent]

hitherto no rodents had died from cancer while receiving c60oo.

Is this true? I don't recall the Baati paper saying that. The indication was that livers were protected from administration of toxins, but as for the chronic toxicity study that had the C60 animals living longer, no cause of death was given for the C60 group.

hav mentioned recently in another thread that the apparent cancer preventive nature of c60 wasn't indicated in the report but has been subsequently conveyed (I had just taken it as read), so probably a good idea to ascertain this source.

[hav]

hitherto no rodents had died from cancer while receiving c60oo.

Is this true? I don't recall the Baati paper saying that. The indication was that livers were protected from administration of toxins, but as for the chronic toxicity study that had the C60 animals living longer, no cause of death was given for the C60 group.

hav mentioned recently in another thread that the apparent cancer preventive nature of c60 wasn't indicated in the report but has been subsequently conveyed (I had just taken it as read), so probably a good idea to ascertain this source.

The first mention I saw of the fact that none of the Baati-study c60 rats died with any tumors was in this thread. Re-reading it now it sounds like he learned of it when he met Dr. Moussa in person previously but didn't feel free to reveal it until Dr. Moussa made reference to it himself in the video interview.

Howard

Edited by hav, 15 November 2013 - 04:31 PM.

[Turnbuckle]

Great!! I was not sure what I could tell, I was planning to ask him next time I meet him (last time we were a bit in a hurry), that is actually the best way: he told on a video what he thinks, that the last rats were sacrificed, had not been found tumors (it was not o nthe paper so I wasn't sure about what I could say yet), and that he sent an application to the ITP. At some point he referred to my small experiment, nice ;-)

That's not much to base a conclusion on. And what is the ITP?

[niner]

Great!! I was not sure what I could tell, I was planning to ask him next time I meet him (last time we were a bit in a hurry), that is actually the best way: he told on a video what he thinks, that the last rats were sacrificed, had not been found tumors (it was not o nthe paper so I wasn't sure about what I could say yet), and that he sent an application to the ITP. At some point he referred to my small experiment, nice ;-)

That's not much to base a conclusion on. And what is the ITP?

Well, it's straight from the horse's mouth, as the old idiom goes... The ITP is the Interventions Testing Program, run out of the NIA. It does careful trials of all manner of compounds, looking for things that will extend life in mice. These are 'gold standard' studies that are run over multiple sites by people who really know how to care for mice and run such experiments. We really need them to look at c60-oo.

[hav]

So if all 3 mice had cancer, there is no longer any rationale for throwing out the first death (or even treating it as a control as some wanted to do). It has to be averaged in with the others.

We all feel differently about this. I don't believe that the first mouse was on C60 long enough to be factored in. It's cancer was probably pre existing and the supplementation of C60 would not have effected its lifespan.
It is troubling that the remaining two mice both developed cancer, even with somewhat extended lifespans.

Given that these mice were already pretty old when they started getting c60, 18 months or so, I wonder how likely it is that they all had preexisting tumors. Are tumors as prevalent in aging mice as they are in rats?

Howard

[Turnbuckle]

So if all 3 mice had cancer, there is no longer any rationale for throwing out the first death (or even treating it as a control as some wanted to do). It has to be averaged in with the others.

We all feel differently about this. I don't believe that the first mouse was on C60 long enough to be factored in. It's cancer was probably pre existing and the supplementation of C60 would not have effected its lifespan.
It is troubling that the remaining two mice both developed cancer, even with somewhat extended lifespans.

Given that these mice were already pretty old when they started getting c60, 18 months or so, I wonder how likely it is that they all had preexisting tumors. Are tumors as prevalent in aging mice as they are in rats?

Howard

The following table is from the paper I linked to in post 464 above. See the first line for controls where the cumulative lifetime risk for mortality or morbidity from a tumor is 25%.

Attached Files

•  Cancer.JPG   52.36KB   20 downloads

Edited by Turnbuckle, 15 November 2013 - 10:03 PM.

[Turnbuckle]

Well, it's straight from the horse's mouth, as the old idiom goes...

As told by the horse to someone else, who then told us.

[hav]

Well, it's straight from the horse's mouth, as the old idiom goes...

As told by the horse to someone else, who then told us.

I think Dr Moussa also mentioned it himself in the video interview.

Howard

[YOLF]

Great!! I was not sure what I could tell, I was planning to ask him next time I meet him (last time we were a bit in a hurry), that is actually the best way: he told on a video what he thinks, that the last rats were sacrificed, had not been found tumors (it was not o nthe paper so I wasn't sure about what I could say yet), and that he sent an application to the ITP. At some point he referred to my small experiment, nice ;-)

That's not much to base a conclusion on. And what is the ITP?

Well, it's straight from the horse's mouth, as the old idiom goes... The ITP is the Interventions Testing Program, run out of the NIA. It does careful trials of all manner of compounds, looking for things that will extend life in mice. These are 'gold standard' studies that are run over multiple sites by people who really know how to care for mice and run such experiments. We really need them to look at c60-oo.

We should start a petition!