21 replies to this topic

[AgeVivo]

See how many we are on these forums; what if we could share the lab work... at home? The idea of MPrize@home is to share mouse life extension tests, which is currently one of the most relevant and lacking thing to do for life extension.

Alone, it can not be done at home: such tests usually involve many mice (eg 80) and very well defined conditions.
But if we distribute the work, discussions, polls and tests showed in this thread suggest that it should in fact be:

• quite easy -- 10 persons having 2 cages of 5 mice to change every other week, no need to be a scientist
• quite fun -- go to your nearest petstore to see how fun mice are
• quite relevant -- heterogeneity of the environment turns out to be an asset

We need to

• be 10 people -- the existing poll has 12 positive answers but it doesn't tell me who
• buy the equipment (approx 100$ per person) and mice and food/litter (approx 300$ per person) ... imminst ??
• choose a first compound to test -- methylene blue or benagene or many other ideas

... and apply for the MPrize . In two years, if it reveals to be not too stupid and scalable (remember, anyone can participate), it could become a key tool to fight aging (eg supplements, what comes out from SENS, or from Michael Rose's long lived flies, combinations, etc). But first we need a test / proof of concept.

Edited by AgeVivo, 02 June 2009 - 11:08 PM.

[AgeVivo]

As clarified by Kismet,
- Can imminst officially support the project?
- Can imminst pay the experiments? (2 groups comparison estimated at 4000$: 400$/person * 10 persons)

[lucid]

Hey agevivo,
Great working trying to get the wheels rolling. Count me in. Once we get a roster of like 10 people lets actually start an experiment!

[caliban]

Thanks for the idea AgeVivo --- the Recorders deadline is June 16th 2009

a few preliminary questions
-- the thread you reference mentions the posibility of other models (nematodes, drosophila) which could be cheaper and have higher turnover.
Are you comitted to mice in this proposal?

if yes
-- the thread discusses mice from petshops and breeders - what would be the approach?
-- the thread discusses uniform versus variable treatment regimes versus variable - what would be the approach?
-- could you elaborate on the non-financial risks that ImmInst might run by endorsing the project?
-- has the M-foundation confirmed that the setup you propose would be eligible to win the prize?

[AgeVivo]

Hi,

-- the thread you reference mentions the posibility of other models (nematodes, drosophila) which could be cheaper and have higher turnover. Are you comitted to mice in this proposal?

indeed this proposal concerns mice only.

The main reason is that mice are mammals and are therefore much more likely to provide good information for humans.

Other reasons are that:
- Doing fly and worm lifespan tests is in fact not so cheap (especially from scratch rather than from a wet lab) nor easy (especially huge impact of light/diapause and contaminations on survival, and need to spend much time per week), nor that fast (not high-throughput), it is already performed in quite many labs and there is already a lot of results, so doing it at home is nice but probably not quite 'necessary/usefull' to boost ant-aging, and it won't attract the attention of many people.
- Concerning mice, that live much longer, experiments are crucially lacking because it is in practice very difficult to organize long-term experiments in a lab, whereas since you are at imminst you could have done several mouse lifespan tests ;-) Moreover pooling accross several sites seems to be relevant, even in standard lab conditions, the best for that is probably at homes --needs to be tested-- and it is hardly impossible in standard labs (the Intervention Testing Program achieves it, bravo). Last but not least, mice are easy to handle --they are now usual pets-- and many people might participate, with or without an interest in aging.

Edited by AgeVivo, 04 June 2009 - 09:24 AM.

[AgeVivo]

-- the thread discusses mice from petshops and breeders - what would be the approach?

Buy materials (cages, food, litter, balls) from petshops and standard pre-aged mice from breeders.

Indeed usual petshops (whether online or near your house) provide materials that are perfectly adapted to homes (rather than labs), and support and advice, and contacts with other pet lovers; but they only provide newborn mice with no certificate.
Petshop mice would be OK to do lifespan tests at home but it is better to use standard (C57BL/6, heterogeneous mice such as CB6F1 x C3D2F1 (HET) could be better but is much less available) and pre-aged (typically 9 months) mice so that we can compare our control lifespans with usual lab lifespans and so that the experiments last 9 months less. Moreover, to have a chance to participate to the MPrize we need birth certificates.
PS: the word "breeders" has two meanings: retired-breeders (cheapest old mice one can get, that we are buying) and the company where we buy them.

-- the thread discusses uniform versus variable treatment regimes versus variable - what would be the approach?

At first we should be simple

In a first proof of concept at least there shall be one control versus one treatment. Each participant will have two cages (one control and one treatment) but will not know which cage is the control and which cage is the treatment. Depending on how things go, we might later want to be more flexible. PS: we will stick to ad libitum feeding: mice can eat as much as they want; caloric restriction requires too much attention

-- could you elaborate on the non-financial risks that ImmInst might run by endorsing the project?

Here are the ones i see, they probably concern participants more than imminst:

a) people allergic to cats are generally allergic to mouse hair as well
b) people working in a mouse facility shall not participate, because they are not allowed to have mice at home
c) if a participant tortures his mice rather than raising them as pets to live long, then animal lovers might react (me first ;-)
d) in some countries (France, perhaps others, need to check) it is required to have a licence to buy standard mice, this could force us to use petshop mice instead (longer experiment)
e) one could be bited by a mouse, but it's not dangerous
f) if one swallows a concentrated treatment, say methylene blue
g) no mouse in microwave

-- has the M-foundation confirmed that the setup you propose would be eligible to win the prize?

Eh, no, I'm contacting them right now...

Once i was supposed to meet them but i couldn't. Here is how MPrize@ home fits in the longevity prize, mouse tagging needs to be discussed.


PS: this main+detailed presentation of answers might not be best, so don't hesitate to suggest better presentations

Edited by AgeVivo, 04 June 2009 - 03:40 PM.

[caliban]

I don't know about others, but I am quite impressed about the cogency and quality of the responses you have provided so far.

My biggest worry remains with the choice of organism. The reasons you cite are very compelling, but the alternative elements also weigh heavily:

Many ImmInst members are young, mobile people who
-- may be moving around a lot
-- are prone to do this on a whim, not fully considering the responsibilities and cost of keeping these pets in carefully controlled conditions for a long time
-- worry what their housemates/new girlfriend will say about the smell
-- are not used to the requirement to keep regular, scientific logs for two years

For what its worth, I have had a quick chat with a senior researcher who specialises in researching laboratory animal behaviour and wellfare, and she thinks that BL6 would make pretty poor pets because they are not companionable. She also suggested that they would die sooner at home for hygiene reasons. However, she is on some kind of 'animal husbandry' list and thinks we could get a lot of useful input from there.

There are a few other questions, but a lot would depend on whether the MPrize would in face accept such home-based experiments. If yes, there is a good reason for looking at mice, if not, maybe one could rethink the choice of organism.

Let us know what the Mprize response is please, and the topic will be discussed at the next recorders meeting.

[Centurion]

This sounds like a fantastic way of getting more people into the scientific mindset. I really like the sound of this.

[AgeVivo]

lucid, centurion, kismet: thx for your support.
Caliban, thank you very much for your implication in searching potential failures, for optimal testing/design of the project

[AgeVivo]

My biggest worry remains with the choice of organism

I see nothing better, let's not forget that mice are just extraordinary for life extension:

• lifespan: they only live 2 to 3 years long (up to 3 in almost sterile conditions; compare with cats or monkeys...) and yet like us they are mammals, with progressive aging that is very close to ours: they are sort of us and won't go to diapause or break like porcelain in our conditions. In our homes they should have a pretty well defined lifespan just as we have a pretty well defined lifespan.
• handling: they are really easy to handle (compare with dogs...). They won't even eat to obesity if you give them sufficient food for 3 weeks! There is hardly any surprise to expect because so much is known about them. And now they are pets (a little less for BL6) and all the equipment is available for home (compare with flies or worms...).

So yes, nothing is fully straightforward, but somehow "it is a gift" to have them (without mice we probably wouldn't have the quality of health we have today) and at this stage i think that for us and our aims it is really blind not to use mice. Now, we are here in imminst and we want to do something concrete: i actually think it's called MPrize@ home. At least try it to see if it is the great thing we are looking for.

Edited by AgeVivo, 09 June 2009 - 08:32 AM.

[AgeVivo]

the alternative elements also weigh heavily:
ImmInst members (...) may (...) not fully considering the responsibilities (...) worry what their housemates/new girlfriend will say

Well i think it is nice mentioning all the fears i had and how things turned out, to me at least:

• time overwhelming?: I tend to plan the most i can per day/week/month, as a result i am often a little short in time. When i started my pre-test of MP @ H, i knew that for other personal reason i would in fact soon have even less time than before (still, i didn't want to wait any longer so i started). The first two weeks i was looking at the cage every evening to check that everything was allright, and within a month or so i had to fix a hole that mice were enlarging (see the thread) that we now know how to overcome. Well, even during that period it was actually nothing compared to any other activity: observing the mice during 5 minutes is already quite much actually. In the contrary, imminst, ebay, emails, can be serious troubles for one's personal time.
• no more vacations?: i went several times away for 2 weeks. Not a problem. Remember to give plenty of food and drink before leaving
• moving house?: i thought several times i would move but it didn't happen. I think this is quite general actually. Otherwise petshops sell containers for when you move, in the train i've seen people with such containers and rats, mice or gerbils. Still, if one does have to stop the experiment, give the mice to a petshop. Logs of half a full experiment HAS value for lifespan tests
• what will my friend(s) say? my wife was particularly afraid i would bring an animal at home (mice!). After one week above the kitchen cupboards she started asking how they looked like;-) She first didn't say much when she saw them, now she finds it funny. We showed the mice to friends, they all found it funny and great so far and many are naturally more at ease than me at the beginning.
• smell?: with 2 mice above kitchen cupboards there is not (well there is when i put my nose in the cage); perhaps i should pre-test 2 cages of 5 mice? if it smells, it might require to change the cages more often, at least when one is not on vacations
• mouse escape?: i'm surprised you did not ask that. i have a leaflet saying how to handle mice. In case of escape, a roll of paper on the floor with a piece of cheese in its center is sufficient to capture the mouse: while the mouse eats the cheese one covers both holes with the two hands, the mouse won't even try to escape. In fact, the mice are used to there cage, a bit afraid when the cage is opened, and don't try to escape
• irresponsible people? bad logs?: Well, it's true that i am motivated so this doesn't happen to me. There are many people that have very long living pets at home, but usually with adults. On one hand I'd tend to think that young US people would be more likely to do this on a whim, on the other hand I'd guess that going to imminst is already a sign of motivation. Perhaps posting about once experiment is the best to avoid irresponsibility or bad logs
• cost?: when, yes it costs, at the beginning (then a petshop visit and a few $ once in a while seems more than normal). I'm afraid this might be blocking for MPrize @ home and that's why we ask for financial support.

So to me it was more fears than reality, but for people wondering to join or not i think it is worth reading those points and going to a petshop to see how it looks like.

she is on some kind of 'animal husbandry' list and thinks we could get a lot of useful input from there.

great!! perhaps you can ask her about whether one is allowed to have BL6 mice at home, i remember that the conditions depends on countries (and states perhaps), and otherwise how to buy mice with a birth certificate, if possible for cheap, and even pre-aged...

There are a few other questions, but a lot would depend on whether the MPrize would in face accept such home-based experiments. If yes, there is a good reason for looking at mice, if not, maybe one could rethink the choice of organism.

Somehow we decide what we do so I'd think that the choice of organism and the acceptance MPrize should not be interdependent. However MPrize acceptance would be nice to have, and more importantly (to me) they are probably of great knowledge to help. In particular i think that the mouse Charlie, whose care-taker received the Reversal prize, was raised at home. I'll keep you informed when i have an answer

Edited by AgeVivo, 09 June 2009 - 09:54 AM.

[AgeVivo]

I'll keep you informed when i have an answer

A few informal discussions have started with the Immortality Institute and the Methuselah Foundation. As far as i understand:

• The concept and anti-aging potential were appreciated
• This major concern was still raised:

  are prone to do this on a whim, not fully considering the responsibilities

  This sounds like a fantastic way of getting more people into the scientific mindset.

  So the question remains whether is it good or not to ask non-scientists to participate: some might forget their mice after some time, mix treatments, not take serious notes... Solutions to reduce the risk are being searched for
• Technical details must be analyzed.
  People were found and contacted who have experience of buying mice or doing mouse lifespan tests or having mice at home

So this is ongoing...

[s123]

[*]This major concern was still raised:

are prone to do this on a whim, not fully considering the responsibilities

This sounds like a fantastic way of getting more people into the scientific mindset.

So the question remains whether is it good or not to ask non-scientists to participate: some might forget their mice after some time, mix treatments, not take serious notes... Solutions to reduce the risk are being searched for

Also the results from professionals can be wrong either by accidental error or deliberate deception for example Hwang Woo-Suk. That's why all scientific results must be confirmed by independent researchers.

[AgeVivo]

results from professionals can be wrong either by accidental error or deliberate deception for example Hwang Woo-Suk

True . I think that having [MPrize@home'] experiments parallelized and discussed over the internet, before and while being done, considerably reduces such risks

Edited by AgeVivo, 14 June 2009 - 06:53 PM.

[AgeVivo]

Caliban, thank you again for your implication and having highlighted concerns. Here are a little deeper answers.


* why mice (rather than flies etc):

My biggest worry remains with the choice of organism

In addition to all my answers above, you will see in this thread http://www.mfoundati...hread.php?t=656 that i was first questionning it like you but that things like this are important:

I'm sorry to always be the sourpuss ... and I really hate to dampen any enthusiasm for anyone thinking of doing any anti-aging research ... still, I don't think that studies on aging in non-mammalian species are very helpful, despite all the hype they've received in recent years. On the one hand, their aging process simply isn't close enough to our own to provide reliable information on our own; and on the other hand, biogerontology now has enough available data on mammalian aging to make ongoing studies in them superfluous.

Drosophila, for instance, don't develop cancer, their entire bodies being composed of post-mitotic cells, and also don't accumulate mitochondrial mutations as they age (1); moreover, there are a zillion things (including many dietary and genetic antioxidant manipulations, or even putting the little bastids in the 'fridge!) that extend their lives that definitely do not work in mammals.

...
1. de Grey AD.[url="http://%5burl="http://www.wspc.com/books/medsci/4714_edi01.html"]http://www.wspc.com/books/medsci/4714_edi01.html[/url]"] Mitochondrial mutations in vertebrate aging[/URL]. In Cutler RG, Rodriguez H (eds). Critical Reviews of Oxidative Stress and Aging: Advances in Basic Science, Diagnostics and Intervention. 2002; River Edge, NJ: World Scientific Publishing, 437-451.

*need for 'serious' MPrize@home participants

Many ImmInst members are young, mobile people who (...) are prone to do this on a whim

In addition to the above answers --that it is not as delicate as it first might appear, that scientists can be wrong by accidental error or deliberate deception, and that the MPrize@home environment reduces such risks-- i have now created a poll in the Methuselah Foundation forums to find serious participants:

http://www.mfoundation.org/forums/showthread.php?t=1368

The MF poll refers to this thread, I hope it helps
Right now i am in the process of contacting various specialists to review technical choices.

Regards.

Edited by AgeVivo, 18 June 2009 - 10:18 AM.

[AgeVivo]

The project is slowly getting real, mainly due to contacts in the real life rather than the Internet. Still, I was expecting many people here to jump on the occasion to really participate against aging. Not just read and write posts. I wonder what imminst really is about...

Anyway, i'll soon buy 3 other mice to check what it is to have 5 mice in a cage. And hopefully some of you reading this post, rather than browsing further or analyzing slight probabilities for this project not to work, decide to contribute against aging: join and participate.

Edited by AgeVivo, 06 August 2009 - 08:26 PM.

[Mind]

The Recorders decided to move this topic into the Ideas Dewar. We think it is a valuable project, however, there has been trouble gaining traction from other Imminst members. We would like to revive this topic before the end of the year and once again see if we can garner more interest.

[Elus]

I'm willing to participate under the following conditions:

• There must be a strict procedural outline. This means: Methylene blue dosage, method of MB administration, type of food, temperature, etc. I do not want to torture the poor animals by giving them toxic doses of MB!
• You tell me what kind of observational data you require. This will help everyone provide specific and uniform data that can be compared.
• You must specify the type of mice we need, and where we should get them from.

Also, I will be moving from my house to college. Should I start this experiment while I am at college, or can I start at my house, and then transfer the mice to a college lab?

Thank you,
Elus Efelier

[EmbraceUnity]

I'm willing to participate under the following conditions:

• There must be a strict procedural outline. This means: Methylene blue dosage, method of MB administration, type of food, temperature, etc. I do not want to torture the poor animals by giving them toxic doses of MB!
• You tell me what kind of observational data you require. This will help everyone provide specific and uniform data that can be compared.
• You must specify the type of mice we need, and where we should get them from.

Also, I will be moving from my house to college. Should I start this experiment while I am at college, or can I start at my house, and then transfer the mice to a college lab?

Thank you,
Elus Efelier

You could certainly start now and move them later. Though I would choose a different substance than methylene blue. You could also use a basket of supplements. Exotic substances like Rapamycin or Spermidine would be great but harder to obtain. I would just look through the regimens in the Lifestyle section of this forum and see what people are doing, and test out if all of this stuff together works synergistically.

I am very interested in Beta Alanine, Curcumin, Cocoa, Green Tea, P5P, and Methyl B-12. Ideally without calorie restriction. Obviously you need a control group, and try to do this double-blind if possible.

To figure out the dosage for mice just figure out the mg/kg used in humans and use the same proportion.

[AgeVivo]

Thank you for your interest! I'm actually starting to receive quite many request like yours now. Technically pretty much everything is decided but it is me who is slowing down the potential beginning of an experiment, because I'd like to do something really usefull out of such a multi-centric home-based procedure:

There must be a strict procedural outline. This means: Methylene blue dosage, method of MB administration, type of food, temperature, etc. I do not want to torture the poor animals by giving them toxic doses of MB!

Methylene blue dosage: 100nM in acidified drinking water: it is several orders of magnitude less than the reported toxic doses, yet it is expected to be sufficient; control: brilliant blue CFC (dose corresponding to the same blue color) in acidified drinking water; see methylene blue thread. In fact you will have a cage "A" and a cage "B" and will receive a treatment "A" and a treatment "B". Food = the very standard chow sold in petshops. Litter: hemp (cheap, mice like it, hinders odors quite well). Temperature/humidity etc: clean well the top of your kitchen cupboard and put your 2 petshop cages there (kitchen are well aired so that the meal you ate yesterday does not smell anymore) (simplest cages as possible in plastic with a minimal number of premade whole on the side; ask your petshop to choose it). The goal is indeed that the environment is a pool or human environments (specification that could not scientifically hold if all mice were in a single place). In such conditions but with a varying set of light treatments, I have been having petshop mice for 18 months that are looking healthy, so it is a practical confirmation that it shouldn't be toxic at all.

You tell me what kind of observational data you require. This will help everyone provide specific and uniform data that can be compared.

Send a picture of your mice when you change their food/litter/water (every week or every other week)

You must specify the type of mice we need, and where we should get them from.

Pre-aged male C56BL/7 mice (e.g. 10 month old: methylene blue or brilliant blue supplementation started at age 12 months), from anywhere (standardized strain), but typically from Jackson laboratories. Technical issue 1: some vendors in some countries only sell those mice to research labs. Technical issue 2: 4 or 6 mice (2 or 3 mice per cage), depending on how whether smell appears or not with 4 mice.

Also, I will be moving from my house to college. Should I start this experiment while I am at college, or can I start at my house, and then transfer the mice to a college lab?

Yes you could.

Now, here is the thing: I'm still hesitating before to start the experiment. Indeed the ITP is now planning to test methylene blue (result expected by mid 2012) plus the ITP and Spindler's lab are now starting many intervention experiments. This was not the case before and it is why MPrize at home was decided. MPrize at home won't test males and females simultaneously etc, its very special feature is the multi-centric human-like environment.

So the most valid reason to do MPrize at home now would be to test everolimus (rapamycin) but among people in the list of MPrize at home no one (including me) has digged much into the feasibility with everolimus.

Best,

AgeVivo.

Edited by AgeVivo, 31 December 2009 - 07:51 AM.

[Elus]

100nM in acidified drinking water

Excuse my ignorance, but how do we get/make acidified drinking water. Is it just drinking water with higher pH?

More questions:

1. Also, would it be okay to have two mice instead of four? 1 mouse in one cage and another mouse in another cage.

2. Can you point me to some papers that show that mythylene is responsible for extending the life of lower organisms?

3. Where can I find the methylene blue thread?

4. Who is ITP that you mentioned in your response?

Thanks.

Edited by Elus Efelier, 31 December 2009 - 10:36 PM.

[AgeVivo]

Elus, sorry for not having answered earlier

100nM in acidified drinking water

how do we get/make acidified drinking water.

water is acidified (pH 2.5–2.7 instead of 7) by addition of hydrochloric acid, as done by the ITP and most (or many at least) animal research facilities. It doesn't reduce lifespan (old paper; if you ask me I'll look for it). During mprize at home s123 would prepare the solutions and send them to participants, so participants would not have to prepare their solutions themselves.

1. Also, would it be okay to have two mice instead of four? 1 mouse in one cage and another mouse in another cage.

mice live less long when alone in their cage (old paper; if you ask me I'll look for it) probably because of lack of stimulation, bad mood, and impossibility to get warm by sleeping next to another mice when needed. For this reason and also because it would require many participants otherwise to reach the required number of animals, it would be better (better, not mandatory because the chosen statistic method would rule out most of such effects) that 4 mice at home (2 per cage) is be a minimum.
However it remains to be checked that it doesn't smell too much when 4 mice are only changed one a week: it is true in my house, but it would be nice to check it in another house too; are you willing to test it in your house? I'm going to ask the question to other persons

2. Can you point me to some papers that show that mythylene is responsible for extending the life of lower organisms? 3. Where can I find the methylene blue thread?

http://www.imminst.o...showtopic=23947 the thread starts with [replicative] life extension of human skin cells (fibroblasts).
The suggested extended lifespan is not obvious: on page 4 you see partial lifespan curve in mice with a trend towards life extension, and mitigated suggested effect in rats. Not obvious to interpret: those were high doses, mice tend to die mostly from cancers, rats have frail kidneys. s123 is thinking of testing the effect on yeast but it has not been started yet. I have read once that methylene blue extends some fish lifespan but there was no reference and it could be due to the fact that methylene blue gets rid of various parasites, fungus and bacteriae. Also you may read that methylene blue reduces lifespan of flies (http://www.ncbi.nlm..../pubmed/8350657) but that is at very high concentrations (approx 10,000 times what we would test).
The positive effect on rodent leucomotor activity, on people's moods and against neurodegenerative disease ("Rember" drug under clinical test by company TauRx), and at high doses malaria and various parasites are more appealing.

http://en.wikipedia..../Methylene_blue is a great recap.
Other methylene blue forums in imminst, effects reported by some members (subjective and questionable): http://www.imminst.o...showtopic=24774 , http://www.imminst.o...showtopic=33660 , http://www.imminst.o...showtopic=33981 , http://www.imminst.o...o...60&start=60

As said, instead of methylene blue we could start with metformin (http://www.imminst.o...showtopic=36918) or everolimus (=rapamycin), I'm not fully decided yet.

4. Who is ITP that you mentioned in your response?

Intervention Testing Program, part of the National Institute on Aging, part of the US National Institute of health
official page: http://www.nia.nih.g...tingProgram.htm
Prof Miller's home page about it: http://www-personal....millerr/ITP.htm
compounds in testing: http://www.nia.nih.g...dsInTesting.htm