25 replies to this topic

[Droplet]

I apologise if this has already been posting but the following fundraiser has popped up on Indiegogo: http://www.indiegogo...-to-live-longer

[reason]

A European and Russian group of researchers are attempting to crowdfund a modest amount for a short-term mouse life span study, using mice that are already old to see if various compounds have much of an effect on slowing aging in old mice. This sort of study design has the advantage of being comparatively cheap as it only runs for half a year or so:

Life is precious. Health too. This is why communities of researchers and citizens dedicate our lives to discover new ways to gain additional years of healthy life. As research progresses, more and more compounds are believed to be good to maintain health over long periods of time. But wouldn't that take decades of clinical trials to verify it? A key step is to do such a clinical trial... in mice : that is what we call a mouse lifespan test. Mouse lifespan tests are infrequent because of their length, their costs and the required environments; but it is crucially needed to continue adding years of healthy life.
Here, we step on the shoulders of giants : by contributing you can help us test a combination of drugs shown to extend healthy lifespan in mice. This experiment has something unique. It is the first time in the world that crowdfunding is used to test a combination of the most potent nongenetic-interventions known to extend the lifespan.
There are *right now* in the lab a sufficient number of aged mice (~20 months old) - male and female - which belong to the C57BL/6 strain to start a lifespan test. The mice will be divided into 2 test groups (females and males) and 2 control groups (24 animals per each group). The test will be blind. The food of the treated mice will contain: 1) An α-adrenergetic receptor blocker (metoprolol). Potential action: Prevents too fast heart beats. 2) An mTOR inhibitor (everolimus, similar action as rapamycin). Potential action: Puts cells in an active and resistant mode. 3) Metformin. Potential action: Normalizes blood and IGF-1 values at low levels. It also has potential similarities with everolimus. 4) Simvastatin. Action: Decreases the amount of LDL cholesterol (considered as 'bad' by some) in the blood. 5) Ramipril: an ACE inhibitor. Action: Prevents hypertension. 6) Aspirin. When small doses are used, it is believed to have reduced side effects while improving blood flow and therefore reducing cardiovascular risks, and potentially also preventing incidence of some cancers.

Link: http://www.indiegogo...to-live-longer/

View the full article at FightAging

[kismet]

Very interesting! Should longecity help out?

[hevok]

Yep, we are doing this. Every contribution is very much appreciated. It would be fantastic when everyone of you could contribute as much as she/he likes and/or at least helps to promote it. Therefore, please spread the word about crowdfunding lifespan experiments in mice!

I know the people involved in this project. They are very passionate about lifespan extension and if they get the sufficient resources, they can do great things for our shared goal of increasing longevity with their laboratory.
Please LongeCity help to make this campaign a success. Help the small mouse to live longer for all of us!

Best regards,
Hevok

[kismet]

I can support and promote it once I have figured out the details. I already asked those involved the questions below and I will report back once I hear from them:

Just like Michael Rae from the SENS Foundation usually is, I'd also be worried about animal husbandry. Is the Ukrainian lab known for healthy controls? When they say "The lifespan of our B6 subline is typically 30-36 months " do they talk about mean or max LS? (or mean 30 and max 36?)

I would not like to waste money on short-lived mice.

What happens if they do not get enough funding?

Did Spindler advise you on dosing & husbandry? May I contact him and/or Dr. Pishel for verification/details?

[Droplet]

I've already donated $10. Not much but if we all did this, the goal would be reached much more quickly.

[niner]

Something is broken with the system that broadcasts FightAging posts to Longecity, and they are getting randomly broken, losing links and then some. Here is the full text of the messed up quote that I copy/pasted from FA:

Life is precious. Health too. This is why communities of researchers and citizens dedicate our lives to discover new ways to gain additional years of healthy life. As research progresses, more and more compounds are believed to be good to maintain health over long periods of time. But wouldn't that take decades of clinical trials to verify it? A key step is to do such a clinical trial... in mice : that is what we call a mouse lifespan test. Mouse lifespan tests are infrequent because of their length, their costs and the required environments; but it is crucially needed to continue adding years of healthy life.
Here, we step on the shoulders of giants : by contributing you can help us test a combination of drugs shown to extend healthy lifespan in mice. This experiment has something unique. It is the first time in the world that crowdfunding is used to test a combination of the most potent nongenetic-interventions known to extend the lifespan.


There are *right now* in the lab a sufficient number of aged mice (~20 months old) - male and female - which belong to the C57BL/6 strain to start a lifespan test. The mice will be divided into 2 test groups (females and males) and 2 control groups (24 animals per each group). The test will be blind. The food of the treated mice will contain: 1) An α-adrenergetic receptor blocker (metoprolol). Potential action: Prevents too fast heart beats. 2) An mTOR inhibitor (everolimus, similar action as rapamycin). Potential action: Puts cells in an active and resistant mode. 3) Metformin. Potential action: Normalizes blood and IGF-1 values at low levels. It also has potential similarities with everolimus. 4) Simvastatin. Action: Decreases the amount of LDL cholesterol (considered as 'bad' by some) in the blood. 5) Ramipril: an ACE inhibitor. Action: Prevents hypertension. 6) Aspirin. When small doses are used, it is believed to have reduced side effects while improving blood flow and therefore reducing cardiovascular risks, and potentially also preventing incidence of some cancers.

I LOVE the idea of crowdfunding LS studies. I HATE the compounds they are using here. This stuff will probably taste so bad that they'll wind up with crypto-CR. Have none of these been tested in the ITP? (I'm pretty sure most have, or something close) Do they really think that there will be magic in the combination? They should try to replicate Baati et al., with C60 olive oil. That's science that really needs doing. For that' I'd kick in my own money, but not for this.

[AgeVivo]

Very interesting! Should longecity help out?

it could help and be well aligned with the C60@home project + mouse lifespan tests is a quasi unavoidable checkpoint for life extension strategies, and the lack of it has been a dead end for many anti-aging approaches

here is the video of the crowdfund: http://www.youtube.com/watch?v=X6Csx6fK9YU

[AgeVivo]

Have none of these been tested in the ITP?

yes, these have been tested with positive results, taken separately, by the ITP and/or Stephen Spindler and his team: the 2 most recognized places for robust mouse life extension test

Do they really think that there will be magic in the combination?

As I understand, the idea is to ask that question. Not all drugs that were shown to robustly extend lifespan were tested in that experiment: only a mixture that humans take for time to time, in order to reduce the risk of side effects of combinations. If there is some magic within some of these treatments it has a chance to be seen. It is not proof, but a try. The greatest mouse life extension so far, a 2 fold one, was obtained a little similarly, by mixing dwarfism and calorie restriction.

They should try to replicate Baati et al., with C60 olive oil. That's science that really needs doing.

Yes, that could have been. The c60@home experiment we are (slowly but really) conducting is great in that it is in rats, so that it is closer to the initial experiment that needs to be reproduced. Any rat researcher here to hear us?

For that' I'd kick in my own money, but not for this.

I'd kick my own money for both and various mammalian lifespan experiments. If you find a rat researcher willing to do the lifespan test if you find the money for it, be sure I'll kick in for a C60 crowdfunding campaign!

Edited by AgeVivo, 14 September 2013 - 08:04 AM.

[AgeVivo]

++. Some people donate, some do the research: everyone collaborates in its way for long lives.

[kismet]

Do they really think that there will be magic in the combination? They should try to replicate Baati et al., with C60 olive oil. That's science that really needs doing. For that' I'd kick in my own money, but not for this.

Yeah, almost all of the suggested drugs extend mean LS.

The NIA is also trying combinations these days, at least for metformin+rapamycin. This crowdfunding study simply adds more compounds and uses older mice. All in all, I'd say we absolutely do need to start testing combinations at some point, as aging is highly heterogenous.

(btw, I have a strong feeling that C60 was rejected by the ITP as a test compound, but I can only speculate as to why...)

Edited by kismet, 16 September 2013 - 10:43 AM.

[niner]

Do they really think that there will be magic in the combination? They should try to replicate Baati et al., with C60 olive oil. That's science that really needs doing. For that' I'd kick in my own money, but not for this.

Yeah, almost all of the suggested drugs extend mean LS.

The NIA is also trying combinations these days, at least for metformin+rapamycin. This crowdfunding study simply adds more compounds and uses older mice. All in all, I'd say we absolutely do need to start testing combinations at some point, as aging is highly heterogenous.

(btw, I have a strong feeling that C60 was rejected by the ITP as a test compound, but I can only speculate as to why...)

I feel like the combination of the kitchen-sink approach and the use mice that have one foot in the grave (and the other foot on a banana peel) means that we won't learn much of anything here, unless there is a miraculously good result. With so many compounds, it's even possible that some of them may work at cross purposes. I don't know how much mechanistic thought went into it.

What gives you the feeling that C60 was rejected? I've heard early rumors to the contrary, though I've not heard anything in a while. C60 has a plausible MOA and one small experiment that showed extraordinary results. I think there's some weird psychology going on here, like no one believes Baati's result because it was too good, or less charitably, they're just too lazy to do the literature work to understand the compound. Well, I'm obviously frustrated. A followup experiment could have been started two years ago (prior to publication but late enough to be aware of the first result), so we've already lost all this time. We desperately need a C60-oo experiment that's run by a lab that people will accept the results from.

[kismet]

Again, in principle late life interventions are a welcome addition. NIA's ITP also ran rapamycin in 20 month old mice and the MFoundation has a dedicated prize:

"Rejuvenation Prize Details

The Rejuvenation Prize is not awarded for the life extension of an individual mouse but for a published, peer-reviewed study. The study must satisfy the following criteria:

1) The treated and control groups must have consisted of at least 20 mice each.

2) The intervention must have commenced at an age at least half of the eventual mean age at death of the longest-lived 10% of the control group. [if I read this correctly 600d old mice would be required at maxLS of 1200d]"

Such experiments are somewhat cheaper and any positive results even more important than early life interventions. Now the question is, are these people capable of running a good study? They are being advised by Dr. Spindler who ran all of this compounds in his mice, although, not in combination. This is definitely a good sign.

I do not believe the C60 data. Yet, the ITP has run even more outrageous experiments, so it might be worth a shot.

Edited by kismet, 17 September 2013 - 10:17 AM.

[niner]

I do not believe the C60 data.

I'm curious as to why you don't believe it. This would require either a major error or fraud to explain the report out of the Moussa lab- is that what you think happened here? If so, then my psychological argument seems to be in play- The data is "too good to believe", therefore there's "no point" in attempting a replication. Are you aware of the published reports of extremely favorable biological activities of various fullerenes in a variety of species? We have a lot of human anecdotal reports that are consistent with the published data, and hard to explain if we don't postulate substantial biological activity of fullerenes.

[kismet]

I'm curious as to why you don't believe it. This would require either a major error or fraud to explain the report out of the Moussa lab- is that what you think happened here? If so, then my psychological argument seems to be in play- The data is "too good to believe", therefore there's "no point" in attempting a replication. Are you aware of the published reports of extremely favorable biological activities of various fullerenes in a variety of species? We have a lot of human anecdotal reports that are consistent with the published data, and hard to explain if we don't postulate substantial biological activity of fullerenes.

Except, I did not say "there's no point". I am just highly skeptical, since the original publication had several problems, at least indicating sloppiness. Most importantly, the lifespans were unrealistic. I have already said that the Institute of Aging has tested even more extraordinary claims, e.g.: three (!) different studies on resveratrol and currently one on estrogen.
Given those problems I would say that this crowdfunding experiment is more promising than C60 research. More generally, however, I share your concerns. Late life interventions in mice are difficult and risky.

As far as high risk-reward is concerned, I do think that a rapamycin-based combination approach in aged mice (as suggested in this crowdfunding campaign) should be right up your alley. Maybe you are thinking in either-or terms when you could support both?

Edited by kismet, 28 September 2013 - 11:11 AM.

[kismet]

Current donations amount to $16,535 out of the 15 000$ goal. It seems like that worked reasonably well! Of course you can still donate to this project (6 days remaining); or the Longecity fundraiser (see the sidebar of the forums). Or both.

I will try to find out if there are any additional experiments that can be carried out with that funding.

Edited by kismet, 15 October 2013 - 05:12 PM.

[kismet]

I will try to find out if there are any additional experiments that can be carried out with that funding.

If you have not heard yet, here's an update:

If we reach $20,000 we will add two additional experimental groups (with [other] drug combinations). Methuselah Foundation is funding a final challenge. If the contributed amount reaches $20,000 in the next 29 hours, Methuselah will contribute another $2,000 to this worthy effort.

Good to see support from the Methuselah Foundation, who are quite involved with mouse life span studies themselves (c.f. MPrize).

[Michael]

All:

Just like Michael Rae from the SENS Foundation usually is, I'd also be worried about animal husbandry.

That's certainly a legitimate issue here: they have Spindler giving advice on husbandry, but the mice are "pre-aged," and they were raised in whatever manner the Ukranian scientists customarily did so for the first 20 mo of their lives.

Still, I was an early donor to this study, which I think has significant merit.

If anyone has missed it: They have met their initial funding goal, and are now looking to increase the power of the study by increasing the number of mice and also potentially to test more agents. They now have a matching-donation deal from the Methuselah Foundation, so any donations you give now would get leveraged into yet more dollars for the study.

I'd encourage you all to give these little critters some money. They've already lived out most of their mousey lives, and now you can give them a chance to live longer and healthier -- and maybe the rest of us, too.

[AgeVivo]

At the time of writing,10 hours remaining for the crowdfunding opened at SENS for the "I'm a little mouse" lifespan test. IF we reach 20k€ tonight, the Methuselah Foundation will add 2k€. If you want to make this possible, quick!!! Click here https://www.indiegog...ntributions/new and contribute . Cheers!

[hevok]

Yes, the last hours of the campaign are running. There are still several mouse left that can be named. We will provide wonderful presents for those that live the longest (I wish I could get it too, I have donated enough and already named one mouse). I can even do a biology course, I am so excited about this. We have also not yet finally decided which treatments will be applied on the new experimental groups. So suggestions are still welcome and if you are one of those that contributed the most (i.e. several hundreds) you will be able to decide on which interventions and gain the unique opportunity to have your idea tested.

http://www.indiegogo...5061?c=activity



All the Best,
Hevok

[Invariant]

Does anyone know how this experiment is coming along? Are there any updates? A website? When are results expected?

 

Thanks!

[Invariant]

Ok I just found this: https://www.indiegog...longer#activity

 

Last update was 6 months ago, but this seems to be the place where they will post updates. I also noticed that backers who donated more than $25, get acces to the online protocol:

"You will get access to online protocol with real-time information about experiment (bio-markers, survival curves, results of necropsia)"

But that option is no longer available because the funding drive is over.

 

Remaining question: when can we expect results?

[niner]

Yeah, it sure seems to have faded away.  I eventually donated some money to them, once they said they were going to add a c60 test.  It would be nice if they could do a small update, just so we know that Vladimir Putin hasn't blown up the lab or something...

[AgeVivo]

Hello, in extremely short, before creating a better communication very soon:

-- the results of the lifespan tests with a mixture of geroprotective drugs will be communicated very soon -- in order to keep the operators blind to treatment groups we prefered not to communicate until the end of the experiment ; but, because this will not affect blindness given current curves, and withoutcreating excitement (risk of semi announcements) we can already say that the results are not particuarly enthusiastic.

-- the c60 mouse lifespan study is starting now, as posted elsewhere in LongeCity. It is 'gradually starting' as mice where not all born at the same date and we want to start treatments ast a given age we enroll mice little by little depending on their date of birth. Results should not be expected before summer 2015.

Cheers!

[Michael]

Ok I just found this: https://www.indiegog...longer#activity

[...]

Remaining question: when can we expect results?

 

 

Yeah, it sure seems to have faded away.  I eventually donated some money to them, once they said they were going to add a c60 test.  It would be nice if they could do a small update, just so we know that Vladimir Putin hasn't blown up the lab or something...

 

They have two cohorts of mice, initiated at ages 15-17 mo and 22-24 mo, respectively. A mouse lives close 30 mo on average, and 36 at maximum, if it's healthy and raised right — so silence may at least indicate that this huge cocktail hasn't turned out to be collectively too toxic, leading to premature death (prima facie and from the Spindler LS studies, a quite reasonable possibility). Barring that, we should be beginning to hear something for the old cohort around now, though it'll be a while for the ones who got a midlife crisis mixed in with their metformin.

[BigPine]

Here's what was posted in mid-November on the website:

 

"Dear Supporters of "I'm a little mouse",

the two series of lifespan experiments under combinations of drugs have just come to their end!

As exchanged (by email; I see that it wasn't indicated on indiegogo) it would have been delicate to announce results during the experiments because the ones handling the mice would have guessed what cages have the placebo and what cages have treatments: it wouldn't have been a blind study anymore. Also, it is obviously easier to communicate based on the whole results.

Therefore, please be prepared to receive a long report by the end of the month, that we are writing now while analyzing the results. In this report, please do not expect extraordinary things; still, what has been done brings some results that are to be put in perspective in the field: you have contributed to some advances in life extension research. Also, in the report there will be other aspects than the two series, but on purpose let us keep such information for the report..."

Unfortunately, no report was posted at the end of last month.