Updates on a Crowdfunded Mouse Life Span Study

For all that I think it isn't an efficient path forward, one likely to produce meaningful results in moving the needle on human life spans, there is considerable interest in testing combinations of existing drugs and various dietary compounds in mice to see if healthy life is extended. I expect that as public interest grows in the prospects for aging research to move from being an investigative to an interventional field, wherein researchers are actively trying to treat aging, we'll only see more of this. There is certainly a sizable portion of the research community who think that the the best path ahead is in fact the pharmaceutical path of drug discovery in search of ways to slightly slow the aging process. To their eyes slightly slowing the aging process is all that is plausible, and adding five healthy years to life by 2035 would be a grand success. Google's Calico initiative looks set to take that path, for example, which I is why I'm not all that hopeful it will produce meaningful results in terms of healthy years gained and ways to help the old suffer less.

There is a considerable overlap between researchers aiming to gently slow aging via drug discovery and researchers whose primary motivation is still investigation, not intervention: to produce a complete catalog of metabolism and how it changes with age, and it's someone else's problem to actually use that data. So we have, for example, the Interventions Testing Program at the NIA. This program was long fought for by researchers tired of the lack of rigor in most mouse life span studies, and the people involved are essentially engaged in replacing a lot of carelessly optimistic past results with the realistic view that very little other than calorie restriction and exercise actually does reliably extend life in mice if you go about the studies carefully. This is good science, but it isn't the road to extended human life spans: it instead has much more to do with understanding the process of aging at a very detailed level. That task is vast and will take a very long time even in this age of computing and biotechnology.

To my eyes the right way to go is the repair approach: build the biotechnologies needed to repair the forms of cellular and molecular damage produced as a side-effect of the normal operation of metabolism, and which clearly distinguish old tissues from young tissues. If you want rejuvenation of the old, a path to adding decades to healthy life, and to eliminate all age-related disease, then repair is the way to go. Fix the damage, don't just tinker with the engines of life in ways that might possibly slow down damage accumulation just a little. This strategic direction can allow researchers to largely bypass the great complexity of the progression of aging and focus instead on fixing things that are already well known and well cataloged. But I say this a lot, and will continue to do so until more than just a small fraction of the research community agree with me.

Back to mice and life span studies: in this day and age institutional research is far from the only way to get things done. Early stage research is becoming quite cheap as the tools of biotechnology improve, and the global economy allows quality scientific work to be performed in locations that are lot less expensive than the US or Western Europe. We have crowdfunding, the internet, and a supportive community, which means that any group of ambitious researchers can raise a few tens of thousands of dollars and set an established lab in the Ukraine to running a set of mouse life span studies. So that happened back in 2013, and has been ongoing since then despite the present geopolitical issues in that part of the world. It is perhaps worth noting that this is the same group that found no effect on longevity from transfusions of young blood plasma into old mice. The studies mentioned below used pre-aged mice, starting at old age as a way to try to discover effects more rapidly, an approach that is fairly widespread.

I am a little mouse and I want to live longer: updates

Dear contributors, we wish you a happy New Year! We are sorry to be taken by a very-expected but very time-consuming c60 lifespan study to digest the data in a way to make the long report we had announced. So, for the New Year and in order for you not to wait longer, please find at least the main results so far:

1) 23 months old C57BL6 mice received a mixture of 6 therapies that had already been reported to extend the lifespan of mice: Aspirin; Everolimus (mTOR inhibitor, similar action as rapamycin); Metoprolol (beta blocker); Metformin (anti-diabetic drug); Simvastatin (lowers LDL cholesterol); Ramipril (ACE inhibitor).

The drugs were given in the food, at doses that had been reported to extend lifespan ... when taken individually. Some people are given that combination of medicines so we hoped that the drug interaction would not be too damaging, and we had wondered if some lifespan synergy within some of these drugs could lead to an overall high lifespan (eg if the different drugs improve different functions). But we observed a lifespan reduction in males and in females.

2) In the food of some remaining females we mixed low doses of 4 medications against cardiovascular conditions: Simvastatin; Thiazide (lowers blood pressure); Losartan potassium (angiotensin receptor blocker, lowers blood pressure); Amlodipine (calcium channel blocker, lowers blood pressure).

The question was: taken at a low-to-medium dose, could these drugs that many aged persons take have some overall preventive effect? We transposed to mice an ongoing polypill clinical trial in the UK, using a basic human-mouse conversion scale. Again, a decrease in lifespan was observed.

3) Adaptations of the first combination of drugs actually extended lifespan!

We started at age 18 months instead of 23 months, reduced the dose (as a function of weight) and gave a) the 6 compounds b) 'only' aspirin+metformin+everolimus. The results are to be analysed in greater details as we haven't analyzed the latest data yet. Also, whatever the refined analysis, we would already like to indicate that it would be good to reproduce the experiment in some other conditions, eg hybrid mice; in particular as the mortality rates of these mice was higher than the first series (but in a consistent way that supports the life extending effect).

4) Ongoing C60 experiments

After many difficulties in setting the experiment (cross-border transportation in current geopolitical times, checking absorption in mice/ detecting C60/correct source of C60, administration tried in food and replaced by gavage, training for gavage and various measures) we have transposed the popular lifespan test with c60 fullerenes reported in rats by Baati et al. to mice (CBA strain, common in the lab) and with more animals (N=17 per group). There are three groups (gavage of water, of olive oil, of C60 dissolved in olive oil), there are ... a lot of health measures and a lot of gavage (at the beginnings of the experiment as administrations are first very frequent and then gradually less frequent). Given that the experiment starts with mid-aged animals, the results are expected for the beginning of 2016.

The original C60 results from a few years back were greeted with some skepticism in the research community, given the very large size of the effect claimed and the small number of animals tested. There was, I think, also a certain annoyance: now that someone had made what was on the face of it an unlikely claim of significant life span extension via administration of C60, then some other group was going to have to waste their time in disproving it. We'll see how that all turns out, I suppose. This is science as it works in practice.

At some point the broad structural classes of research illustrated by the Interventions Testing Program and this crowdfunded mouse study will meet in the middle, and the process of funding and organizing scientific programs will be a far more complicated, dynamic, and public affair than is presently the case. I think this will be for the better. All that we have we owe to science, and a majority of the public thinks all too little of the work that will determine whether they live in good health or suffer and die a few decades from now. The more they can see what is going on the better for all of us in the end, I think.


AFAIK the parabiosis experiments had a continuous blood cross flow between mice.

In this experiment they "injected once intravenously and once intraperitoneally per week for 16 months" ... probably you get similar results if a propeller has a speed of 1 rpm ... then wonder why the airplane is not taking off.

Posted by: Adrian Crisan at January 1st, 2015 9:08 PM

You talk a lot about drugs that alter metabolism only slowing the aging process, but you are making assumptions that are not necessarily warranted. As far as I can tell, the body naturally has systems in place for the removal of many kinds of damage, and as long as damage is inflicted at a rate slower than the body can naturally remove it, the body will actually repair existing damage rather than merely getting damaged more slowly.

Of course not all forms of aging damage are like that. But for those that are, we need to consider the possibility of slowing damage to a rate low enough that the body can remove it itself.

Anyway, I'm really disappointed this combination therapy didn't work. It will not be possible to do much about aging unless we can address all the different forms of damage. So we need things to work together similar to how they work individually, and it is frustrating when they don't.

The other annoying thing about these randomised control trials is that they give you a strange answer without telling you why or how. Still, it's useful to know it doesn't work.

Posted by: Carl at January 1st, 2015 10:03 PM

@Carl - You're making a large assumption of your own: that a significant enough percentage of the damage that is the root cause of aging is repaired by the body, just for some reason at a rate that is too slow to keep a lid on this damage and keep the human body from aging at all.

Reason is theorizing that your body produces garbage (damage) that is never removed, you are hoping that damage is removed, just at too slow a rate to prevent it building up, therefore all we have to do is modify metabolism enough to slow the rate down to the rate at which it is removed. This seems to be veering into the realm of wishful thinking to me. If the body already has these repair mechanisms, why don't people with favorable mutations that slow the rate of metabolic damage already exist? Where are these lucky semi-immortal non aging individuals who live for hundreds of years, not just 4 or so extra years?

Your body does repair a lot of damage, but only if that damage affects your reproductive fitness. Damage that occurs after the reproductive period of an animals life is not under any selection pressure to be gotten rid of unfortunately.

Posted by: Jim at January 1st, 2015 11:51 PM

I'm glad to see that someone is testing c60 in olive oil again. That's very interesting. Thanks for the news. I hope that you guys will keep us updated on how that goes. Of course, I guess that we'll be waiting a year to hear the results.

Thanks again,

Posted by: Nathan at January 2nd, 2015 12:17 PM

No, I'm not making an assumption. We know that some official SENS forms of damage can be removed by metabolism, such as Amyloid Beta. We've also seen at SENS conferences that some lipofuscin accumulation can be removed by altering metabolism. And it's obvious that metabolism can remove senescent cells, etc.
It's good that Reason and you are looking at engineering repair of damage that your body has no system for repairing. But you can't dogmatically assume that is always the case.

Posted by: Carl at January 3rd, 2015 10:55 PM

@Carl - So you're not assuming that we can modify metabolism so that the rate of damage accumulation is slowed down, you're assuming that we can modify metabolism so that the rate at which it is removed (in cases it is removed) is speed up enough to cope indefinitely...

However it seems like metabolism is a bit of a mirror maze, and is certainly nowhere near fully understood at present. Modifying one part of it often causes negative side effects elsewhere. For example statins lower LDL levels, but do result in side effects. Which is why the SENS Foundation's proposal to use enzymes to remove oxidized LDL from foam cells is superior (at least in theory).

The point I was trying to (badly) make in my above comment was that it seems logical that some natural repair systems are constrained by negative side effects long before they reach a level where they are keeping a lid on a type of damage permanently. Senescent and cancer cells are removed, but altering 'metabolism' to boost the general immune system is probably constrained by the chances of getting auto-immune disease. If there was only upside to boosting certain metabolic processes, then evolution would probably have done so already. You could make the argument that it hasn't bothered, because individuals in the wild would die on average before seeing the beneficial effects of mutations altering these pathways, so there would be no selective pressure for these mutations...

But the main reason people don't think altering metabolism will do much is its complexity. It seems far easier to side step this problem by removing damage directly than creating an improved metabolism.

Posted by: Jim at January 4th, 2015 3:03 AM

Also it seems Reason is not knocking temporarily modifying a small part of metabolism to remove damage, he is knocking trying to understand how metabolism causes damage, and then how that damage eventually sends metabolism haywire resulting in the diseases of aging at a molecular and genetic level. It would be nice to know this, but it is going to take decades and maybe even centuries. beside the time needed for this task, it probably won't produce much more knowledge necessary for reversing aging.

You could analyze the origins of the first world war at the level of nation states and their leaders, or as a huge mass of quarks and leptons moving about. The later level is more detailed, but would also be a huge waste of time and wouldn't tell you much you didn't already know.

Posted by: Jim at January 4th, 2015 3:13 AM

It's like anything else, you don't understand how everything about a machines molecular structure functions to make it more efficient before being able to repair it in the first place.

Studying how to improve metabolism is like figuring out how to make the body age more efficiently without knowing how to make the body last long enough to merit worth to this in the first place. What's the point of figuring out how a hybrid car works when you don't know how to even construct the battery, what's the point of increasing the efficiency of the heart if you don't know how to fix the building foam cells

Posted by: thatoneperson at January 5th, 2015 6:45 AM

They both have value mind you, it's just that, one step has more importance as a initial step then the other.

Posted by: thatoneperson at January 5th, 2015 6:47 AM

Have been taking C60 (Vaughter) for 5 months (1/2 tsp/day). I had hoped it would reverse the damaging effects of Accutane taken when I was 27 (now 58). No change in inflammation (usually very bad this time of year anyway, so much so I cannot exercise very much). Most disturbing is in the past month I have noted an alarming decrease in cognitive function; I cannot remember simple words. As C60 is the only new addition and as there has been no positive physical effects from it, combined with the mental degeneration, I can only think C60 is not helping at all and I am discontinuing it. Hopefully my normal regimen of Acetyl-L-Carnitine, ALA and Omega-3 oils can reverse any possible damage.

Posted by: Dawn Wessel at March 10th, 2015 5:55 AM

Hi Dawn, how are you now? I have been thinking about you and your unexpected cognitive degeneration. Did you have any improvement?

Posted by: Wes Dawin at July 5th, 2015 8:10 PM

We need to consider the probability that our own genome is programmed to kill us in old age; as in Grow, Reproduce, Die! Mutations in the AGE1 and the AGE2 gene in
C. elegans increase lifespans. Subsequent genetic modification (PI3K-null mutation) to C. elegans was shown to extend maximum life span tenfold. Yes, that is a lifespan 10 times longer than normal. No other intervention in any animal even comes close. If there were an evolutionary advantage to a longer lifespan, mutations in the genome of C. elegans for a longer lifespan would have long since become the norm. The AGE1 and the AGE2 genes are also found as homologs in other animals, including humans. As far as I can tell, they have no other purpose in life except to kill us in old age. The fact is evolution wants old people to die. Is it impossible for the human body to repair damage in old age? Repair can certainly be made. If you don't think so, just take any old person who is not completely crippled to the gym and work him out for a month. You will see a very rapid increase in strength, caused by the repair of minor muscle damage due to weightlifting. Cheers!

Posted by: Jerry Collins at February 20th, 2016 7:56 PM

Anyone have updates from this study...? it just seemed to stop a few years back.

Posted by: Darren at July 24th, 2017 4:09 PM

I am also curios what happened to the c60 study...
it was announced for the beginning ob 2016 - so where is it?

Posted by: anna at August 15th, 2017 1:48 PM
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