LONGECITY

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

This is why (I now feel) there is not a compelling case to discount the first death from results. It would seem a very real possibility, from AV’s results, that when the administration of c60oo in mice (commenced at a late age) is studied once again, a large proportion will die from tumours - an unfulfilled optimism kindled from Baati et al was that AV’s study would also be cancer-free. As such the data somewhat tentatively suggests an experiment operating under similar conditions will largely shift in emphasis to not one of c60oo’s effect on longevity exclusive of cancer (as it transpired in Baati), but rather, unfortunately, very much inclusive of it.

If, in another (larger) study introducing c60oo to older mice, there exists a sample of rodent deaths recorded free of cancer then one might reasonably syphon off this data and use it conjugation with the Baati results (& hopefully, comparable but larger studies) to plot the impact of c60 on longevity at various stages in rodent life without the confounding effect of cancer. It would surely be more meaningful to analyse the action of c60oo on the longevity of mice separately when cancer is and isn’t present at death. If true* that none of Baati rats died were stricken with cancer then it would, I feel, be misleading to add AV’s results to (or explicitly inform on) Baati; but rather they should stand alone and (all three mice) serve as initial data for a larger sample of work constructed under similar conditions to AV’s experiment.

As niner points out, the possibility that c60 slows cancer and extends life in older mice is very much live - there is a reasonable consensus that two of the mice markedly outperformed (compare to norm) expectations in getting to 2.75 years. So it is quite possible there is an effect of c60oo on the progression and or the precipitation of tumours in mice - an effect (the progression at least) which would not have been readily inferred from Baati, even if it is only done so weakly in AV’s work.

* Having read the quotes in this thread, it isn’t clear to me that prof Moussa’s attributed quote (filtered from AV) appears to claim all rats were cancer free, but rather the one’s that were killed to end the experiment. It would be good to clear that up (or does he explicitly say ‘none of the rats’ in the interview?)
Edited by ambivalent, 19 November 2013 - 03:59 AM.

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%.

so although there were tumours present at death in all three mice; we can't confirm that the tumours were the cause of death in all instances, or do we? If not, do we know the likelihood of tumours being present in controls, at death, rather than explicitly accounting for the cause of death (which here was 25%)?

it might be useful to see some experimentation done on rats of greater age, even older than agevivo's. if controls were included, this type of experiment could possibly give some useful results within just a few months time. at least this would tell us if there is any life extending property when taking c60-oo in advanced age.

it might be useful to see some experimentation done on rats of greater age, even older than agevivo's. if controls were included, this type of experiment could possibly give some useful results within just a few months time. at least this would tell us if there is any life extending property when taking c60-oo in advanced age.

This is harder to do than you might think. The older the animals are at the start, the smaller the life extension effect is expected to be, while at the same time the animals are more diverse with respect to their health. In other words, some will have started developing fatal conditions, while others will be in better shape. Because of this combination of higher noise and smaller effect, you need a lot more animals to get adequate statistics.

A study like this is now underway, as a small part of the recent crowdfunded experiment trying a combination of interventions on older animals. While it's relatively small, it will at least be controlled and performed in a professional facility.

Just for anyone new following this thread, could someone please list the age of AV's mice, in months, at time of death.

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%.

so although there were tumours present at death in all three mice; we can't confirm that the tumours were the cause of death in all instances, or do we? If not, do we know the likelihood of tumours being present in controls, at death, rather than explicitly accounting for the cause of death (which here was 25%)?

The numbers in that table are not reliable for what we're trying to determine, which is how unusual AgeVivo's result was in seeing all 3 of his mice die with tumors present. The probability calculation, even if correctly done, would not tell us the anything about what mice that survive childbirth, lab accidents, feeding mishaps, wounds from physical attacks by other mice, etc, will eventually die of. We're only interested in comparing causes of death related to health and disease. Hard to exclude the irrelevant without the underlying counts. [Also, see: this! ... discovery 10 years later that the 2001 calculations were apparently tainted by bad data.]

Doing a controlled study would help allot. Starting with younger mice would minimize the chance of preexisting tumors.

Howard

Just for anyone new following this thread, could someone please list the age of AV's mice, in months, at time of death.

From earlier posts:

c60 treatment commenced at age 18 months for all 3 female mice. See: post #1 of necropsy thread.

mouse #1 died on Oct 9, 2012 at age 22 mos 9 days. See: post #146
mouse #2 died on Jul 21, 2013 at age 31.5 mos. See: post #374
mouse #3 died on Jul 30, 2013 ... see: post #423 (I calculate approximately 31 mos 24 days)

Howard

This site mentions 32 month old mice. Could be interesting reading:

This essay presents some practical advice and suggestions for those who wish to use mice and rats in experiments on the biology of aging.

A study like this is now underway, as a small part of the recent crowdfunded experiment trying a combination of interventions on older animals. While it's relatively small, it will at least be controlled and performed in a professional facility.

I think I've missed this. Where can we get more information about this study? What other ongoing studies are you aware of?

I think niner was referring to something that actually did not happen.

I came across these papers exploring the effect of fasting on improved functional recovery after spinal chord injury in rats and mice

 

 

http://www.ncbi.nlm....les/PMC3119327/


http://www.ncbi.nlm....pubmed/21410319

 

It worked well for the rats but not for the mice. I believe the paper infers mice do not experience ketosis while fasting, as such they experience no improvement in recovery. My (crude) understanding is that there are epigentic changes when we (and rats!) fast and it is theorised on here an epigentic theory of action for c60. Might it be that the rat's metabolism facilitaties the c60 epigentic changes, whereas the mouses's metabolism does not?

Edited by ambivalent, 12 May 2014 - 08:17 PM.

Very interesting Ambivalent!

I came across these papers exploring the effect of fasting on improved functional recovery after spinal chord injury in rats and mice

 

 

http://www.ncbi.nlm....les/PMC3119327/


http://www.ncbi.nlm....pubmed/21410319

 

It worked well for the rats but not for the mice. I believe the paper infers mice do not experience ketosis while fasting, as such they experience no improvement in recovery. My (crude) understanding is that there are epigentic changes when we (and rats!) fast and it is theorised on here an epigentic theory of action for c60. Might it be that the rat's metabolism facilitaties the c60 epigentic changes, whereas the mouses's metabolism does not?

 

A very good find/thinking ambivalent!

Lets hope that some of the more biologically educated people here see this and throw their hats in the ring.

Could it be that mice are not candidates for C60oo experiments!???
 

Edited by Logic, 06 June 2014 - 08:29 AM.

I came across these papers exploring the effect of fasting on improved functional recovery after spinal chord injury in rats and mice
 
http://www.ncbi.nlm....les/PMC3119327/

http://www.ncbi.nlm....pubmed/21410319

It worked well for the rats but not for the mice. I believe the paper infers mice do not experience ketosis while fasting, as such they experience no improvement in recovery. My (crude) understanding is that there are epigentic changes when we (and rats!) fast and it is theorised on here an epigentic theory of action for c60. Might it be that the rat's metabolism facilitaties the c60 epigentic changes, whereas the mouses's metabolism does not?

 
In the 2nd abstract, they say that the mice didn't experience an increase in ketone bodies under EODF, although the rats did. The exact connection between ketosis and improvement in spinal cord injury is murky. They chalk it up to "differences in the metabolic response to IF". I don't think that there's any evidence for an epigenetic explanation for the different outcome of SCI between rats and mice, nor is there any evidence that c60oo's MoA is epigenetic. Thus making the connection between these papers and c60 on the basis of epigenetics requires two speculations to both be realized, which is pretty unlikely. On the other hand, differences in metabolic response to IF do at least raise the possibility that rats and mice will have significantly different responses to something that alters their energy metabolism. This raises the specter that c60oo lifespan tests in mice may have a substantially different outcome compared to rats. Of the three c60oo trials underway (or soon to be), the two that have been going on the longest are in rats. The trial that is supposed to start very soon in Kiev is going to be in mice. Baati used rats. Eventually we should get this sorted out, but it's going to take some time.

Thx Niner.

Might have to do with telomere length differences between rats and mice.  This hasn't been published yet but finds a relationship between longer telomeres and better outcomes after chronic spinal cord injury:

 

http://www.atsjourna...Abstracts.A3886

 

This study indicates there is often dna damage from the oxidative stress caused by a spinal cord injury and that antioxidants may help in therapy:

 

http://www.ncbi.nlm....les/PMC3619128/

 

A variety of known anti-oxidants have shown efficacy as therapies for SCI, providing both cellular protection and improved behavioral outcomes in experimental models and clinical trials (reviewed in (Hall, 2011; Jia et al., 2012)). One such anti-oxidant therapy is methylprednisolone (MP) which has been shown to provide a small but significant neurological benefit when given at high doses after acute SCI in humans (Bracken et al., 1990; Bracken et al., 1997). However, its efficacy remains under intense debate and administration of high dose MP is associated with a number of adverse side effects including immunosuppression and increased risk of infection (e.g. pneumonia, urinary tract infection, sepsis, etc.), hyperglycemia, adrenal insufficiency, and even death (Suberviola et al., 2008). Therefore, there is still a significant need for more effective and safer antioxidants for the treatment of spinal cord injury. Our group and others have shown that estrogen (17β-estradiol), a potent antioxidant and scavenger of free radicals, has neuroprotective effects following spinal cord injury (Samantaray et al., 2011; Sribnick et al., 2006; Sribnick et al., 2010; Yune et al., 2004).

 

C60 may be the safer and superior antioxidant that they're looking for.

 

Howard

 

 

Just for anyone new following this thread, could someone please list the age of AV's mice, in months, at time of death.

From earlier posts:

c60 treatment commenced at age 18 months for all 3 female mice. See: post #1 of necropsy thread.

mouse #1 died on Oct 9, 2012 at age 22 mos 9 days. See: post #146
mouse #2 died on Jul 21, 2013 at age 31.5 mos. See: post #374
mouse #3 died on Jul 30, 2013 ... see: post #423 (I calculate approximately 31 mos 24 days)

Howard

 

When were AV's mice really born? Based on those dates and lifespan calculations, I get the following birth dates:

 

Mouse 1: November 30, 2010

Mouse 2: December 5, 2010

Mouse 3: December 6, 2010

 

However, post #48 says something different:

"I have pictures from when I bought the mice: january 28th 2011. They were probably 3-4 week old so the experiment started at age 18th month, with a precision of about one week"

 

That would imply they were born on the first week of January 2011, which is a month off the stated ages of 22 mos 9 days, 31.5 mos, and 31 mos 24 days, respectively.

Of note is this site:  http://research.jax....LifeStudy2.html

 

it shows the median life span of 12 strains of lab mice

 

The average across all twelve is 23.48 months using 30.5 days per month =(year 366 days)

 

The longest lived 2 individuals of each strain had an average lifespan of 30.38 and 32.20 respectively

 

Based on the chart data points between 16 and 20 individuals were in each strain cohort

 

for approximately 200 individuals.

 

It is interesting that 2 of 3 of the C60OO mice referred to in this thread

 

met or exceeded the average lifespan of the 24 longest lived out of approximately 200 mice

Edited by sensei, 13 December 2014 - 08:47 PM.

Of note is this site:  http://research.jax....LifeStudy2.html

 

it shows the median life span of 12 strains of lab mice

 

The average across all twelve is 23.48 months using 30.5 days per month =(year 366 days)

 

The longest lived 2 individuals of each strain had an average lifespan of 30.38 and 32.20 respectively

 

Based on the chart data points between 16 and 20 individuals were in each strain cohort

 

for approximately 200 individuals.

 

It is interesting that 2 of 3 of the C60OO mice referred to in this thread

 

met or exceeded the average lifespan of the 24 longest lived out of approximately 200 mice

Post #62 on this thread has another data point: 

http://www.longecity...ng-my-rats-c60/

 

Two rats in that experiment died so far. One (Willow) lived longer than average considering the circumstances involved:

"Willow was a rescue rat, and came into the rescue with a very large group. Most of those rats that I was able to keep tabs on have already passed away ... I have three other rats from that group, all still living, and they have generally healthy."

 

The other one (Pip) actually lived longer than any of AgeVivo's 3 rats, assuming those rats were born in early January. Pip lived from 4/26/12 - 12/3/14, which is 951 days (31.2 months).

Hello, I bought the 3 mice alltogether and they were of the same age but I the shop could only say what week, not what day. I think it is early December (I bought them on vacations, certainly Christmas vacations; I guess January 28th is a typo, there must be one number too much). Sorry for the lack of precision/typo (was trying to run the mini trial in addition to family/job/other things in life).

As a newbie I got kind of overwhelmed with the volume of this topic but it seems that your experiment was to shed light on if C60 prolonged life in mice?  The outcome appeared to be that all the mice died with cancer, but you could not be sure if the cancer killed them or if they died from other causes with cancer?  

  The earlier study published was corrected as the data was faulty and other studies on cancer and old age have shown that in humans after age 80 cancer deaths seem to flatline or about 25% of the elderly will develop cancer in their lifetime.

  One of the questions brought up in your experiment was is cancer increased or decreased with the administration of C60 in relationship to age or when the C60 was started?

  I do not have a research background so I hope I understood the most interesting study that you undertook.  You also refer to other studies on this topic of cancer being undertaken?  Have any of them been concluded?

   This dilema of cure or cause has also been hotly debated with TA-65, and I believe their is a current lawsuit pending on this topic although there is also a cancer drug Geron developed using Astragalus--so--go figure? 

McK, it's very common for mice to die of cancer, or to at least have it when they die of something else.  This experiment had no controls, so you can't really use it to imply causality.  There was just a paper that came out looking at doxoribicin and a c60 colloid in water.  This version of c60 was moderately anti-cancer in the model they used.  There are other studies that have not yet concluded. 

A lot of effort has been expended on trying to draw some conclusions from this experiment, but it's all a wasted effort. Here we have 3 mice of uncertain age, unknown pedigree, and no controls. They did not live unusually long for mice, and they all died with cancer. This would seemingly be a bad thing, but without controls no conclusions can be drawn.

Turnbuckle is correct, but AgeVivo's experiment is still praiseworthy. He went out of his way to try something similar to Baati. Bravo for being a leader.

There were talks of larger studies happening in the past (years ago).  What ever happened to those?  Are they actually ongoing or did it not go anywhere?

There were talks of larger studies happening in the past (years ago).  What ever happened to those?  Are they actually ongoing or did it not go anywhere?

 

At least one person with a somewhat large number of pet rats/mice was attempting a study. There have been some difficulties, last I read, because it is not a lab environment. http://www.longecity...ebelles-rattie/

Fantastically Great Job!

The pictures are attachments. Are they only visible to members? That seems wrong... (I can see them, but that might be mod super-powers...)

Mod-super-powers, lmao.

 

Nice job OP!

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.

 

It's also possible the cancer was caused by the C60.   I'm not saying it was, but to consider all possibilities that should be included as one.

Good post Pone; yes we must face the possibility that C60 is neither protective and may actually be a factor in cancer development.  In humans I think the numbers are that one in eight will have cancer over their lifetime, all these mice had it.

I was considering trying C60 but I think I will stick to my TA-65 and Stem Cell 100 by Lifecode for now.

Good post Pone; yes we must face the possibility that C60 is neither protective and may actually be a factor in cancer development.  In humans I think the numbers are that one in eight will have cancer over their lifetime, all these mice had it.

I was considering trying C60 but I think I will stick to my TA-65 and Stem Cell 100 by Lifecode for now.

 

 

In mice it is one in four. And yes, that the C60/EVOO actually caused the cancer is certainly a possibility. I was never clear on where this C60 came from. Did AgeVivo make it himself, or did he get it from the researchers, and if the latter, was this from their original batch? Because olive oil does go rancid and I doubt even C60 will protect it forever. And as rancid oil is known to cause cancer in mice, it could be the oil and not the C60 that caused the cancer.

Edited by Turnbuckle, 25 December 2014 - 04:56 PM.