Major Mouse Testing Program Launches

The news for today is that the Major Mouse Testing Program has launched. This is an initiative set up by advocates and researchers associated with the non-profit International Longevity Alliance, and is intended to speed up testing and replication of promising potential treatments for aging in mice - though of course there are considerable differences by scientific faction as to just what is considered a promising potential treatment. The Major Mouse folk will be crowdfunding their efforts, building on the growing experience in the community in raising funds for research this way in recent years.

Within the SENS portfolio of repair biotechnologies there are actually few options presently at the point of viable interventions that are both low cost and worth trying: senescent cell clearance has a number of potential approaches, mitochondrial DNA repair is getting close, though not on the cost front due to the reagents needed, there have been demonstrations of improved lysosomal function in old animals leading to functional rejuvenation of tissues, and so on. We can argue about which portions of the very broad field of stem cell medicine might be considered rejuvenation biotechnology at this point. Even in this comparatively small present portfolio of practical options there is far too little work taking place in mice, however. There should be dozens of studies running for senescent cell clearance alone given the potential it shows. This is just considering SENS, however. For people who are more interested in the mainstream approach of trying drugs to slow aging, such as the development of calorie restriction mimetics, autophagy enhancers, and the like, for all that this is likely an expensive way to produce marginal benefits, there is an enormous array of things to test that are not being tested.

A lot of compounds and drugs have been tested in mice (and other laboratory species) in the past few decades. Most of these results have to be thrown out, especially those showing modest extension of lifespan, as few of those studies controlled adequately for inadvertent calorie restriction or were otherwise robust enough to pass muster. Calorie restriction has a large effect on aging and lifespan in short-lived animals, larger than almost any other intervention tested to date: if a compound makes animals nauseous, they will eat less and live longer, but there are many other ways to accidentally create incorrect data. The National Institute on Aging runs the Interventions Testing Program (ITP), which conducts very robust life span studies in mice. The most important output of this program, to my mind, is that it has demonstrated that most currently available interventions have tiny positive effects at best. Hopefully it has served to convince more people that developing drugs to alter metabolism with the aim of slowing aging is a road to nowhere, and that a different approach - i.e. SENS-like therapies that repair the damage that causes aging - is needed.

The Major Mouse Testing Program exists because the ITP is slow, and very few groups outside the ITP are doing anything of this nature. The ITP staff test only a few options in any given year, and adventurous tests such as "let's combine everything shown to extend life so far and see what happens," or "let's try something related to SENS" are never going to be on the agenda at the NIA, or at least not for the foreseeable future. The Major Mouse folk are not so constrained, however.

Major Mouse Testing Program

We live in exciting times - for the first time in human history extending healthy human lifespan is rapidly becoming a realistic prospect. Scientific breakthroughs in research mean we could soon be living healthy, active lives for much longer than people do now. Some drugs tested have been found to increase mouse lifespan such as Metformin and Rapamycin for example and are considered for human testing. Many more substances have never been tested and we do not know if they might extend healthy lifespan. More studies are needed before we can move onto human tests - and ultimately medicines that people can use. What happens next depends on how much more quality research is being done by scientists - and that research needs funding. We are launching an ambitious international project, called the Major Mouse Testing Programme (MMTP) via a crowdfunding campaign to support this important work.

Right now very few high impact studies investigating lifespan are initiated each year - and with around one in ten promising substances tested so far found to actually make mice live longer, this is painfully slow progress. We are working to redress this situation and with an international team of dedicated lead researchers, three high quality laboratories and a dedicated team, we are hoping to make a real contribution to the field of regenerative medicine. The Major Mouse Testing Programme is a project that aims to speed up the pace of progress up by rapidly testing longevity interventions - meaning research which would have taken 100 years at today's rate can be done in five. It is also plausible that some interventions, when combined could have a synergy where the effects are greater than the individual compounds, this has certainly been the case for senescent cell clearance with Dasatinib and Quercetin. It is likely there are more synergies to be discovered and this is where the MMTP plans to push forward, not only testing single interventions but also combinations to seek out these powerful combinations.

We have opted to test with mice partly due to the costs involved and mouse studies are also considerably easier to organize and are the usual starting point prior to moving into higher animals such as rabbits, dogs and ultimately humans. Organisations such as the FDA for example also usually require substantial animal data prior to approving any clinical trials involving people so this is another reason for choosing to begin here. The initial phase of the project has a limited number of substances to be tested, but importantly it will demonstrate that the team is able to conduct the large scale intervention studies testing more complicated and expensive interventions demand. As part of the current project we are planning to test at least two substances. One which is known to increase mouse lifespan (Rapamycin) to show that the labs can generate the same consistently high quality data. This will serve as our positive control group to ensure all three labs are operating to the same rigorous high standards and are producing the same data.

You can see the first set of interventions the team plans to test in their research portfolio, along with explanations as to why these drugs have been chosen. You'll see that the senolytic drug combination to clear senescence cells reported earlier this year is on the list. Running a replication study there is a useful thing to do, I'd say, given that the original researchers don't seem all that interested in following up on their work with a life span study.

Comments

@Steve H

Steve, if ever you read this, ; D I hope your mouse testing program works out great!, it will surely improve health of mice (and humans, hopeful)! On the website of your testing program it says ''We will test:
Rapamycin, Quercetin, Dasatinib, Oxytocin, ALK5 inhibiot II, compound, 5, 6, 7, 8, 9. I am highly curious about these mysterious unknown number compounds; but especially I don't understand why there is not a 10th compound : D...Do you know them ? It will improve health and the mice lifespan, on your website they say ''we will see synergy, like in quercetin and dasatinib'', I hope that, because another study that fed a Huge Cocktail of compounds stuff to mice did not synergize at all for it increased mice lifespan by around 15-30%. I think the reason is that certain of these compounds act on similar redundant pathways, hence when you miexed them in they don't synergize for they act through same pathway. Studies have show huge results something using a Single compound alone vs 50 together, becaus that single one - hit the right buttons. Adding more can creat what I call ''competition'' for pathways (compounds compete for receptors and gene pahtways), thus muddying results. Stil, I hope it's not the case and they can Synergize like The Energizer Bunny :X and make Some (Real) Results happen. I'm guessing about 30% extension of lifespan and healthspan from the compounds on website. just wild uneducated guess.

@Reason

'' ...I'd say, given that the original researchers don't seem all that interested in following up on their work with a life span study.''

Hi Reason ! I think that is very revealing/telling though, why would they not want to continue, perhaps, money, time, resources or just not want to...I believe it has something to do with them not entirely believing in it increasing maximum lifespan but only Healthspan (by inflammaging reduction) and a good bit of Average lifespan (they just don' t think it's worth finding out some fractional percentage increase they already know about or guess vaguely), they would be thrilled to follow through on their own work if they were certain without shred of doubt that it would greatly extend maximum lifespan or make huge gains; their refusal or lack of interest is telling sign they are convinced it does mild effect on lifespan or Very doubtful about that. The Doubt is Strong is Them. After all, they are the original researchers and finders of these results, it's theirs. Others can continue their work, but I'm willing to bet they want be proven wrong because they know it's not going to happen (that they will extend lifespan dramatically using their findings, they aleardy know these compounds will extend health/average lifespan a bit or even moderately, they just won't bother for something like that when they will relegate it to CR effect, it seems like a 'non-news' for them).

Posted by: CANanonymity at December 23rd, 2015 7:12 PM

God luck with this project!

Is there an estimate of how much each test will cost? Also, it would be nice to have a funding bar showing 20% complete, 40% complete or whatever.

Also, what will they do if they win the MPrize?

Posted by: Antonio at December 24th, 2015 4:51 AM

BTW, grey text over light-grey background is difficult and tiring to read.

Posted by: Antonio at December 24th, 2015 4:56 AM

@Reason firstly thank you kindly for the article it is much appreciated, we have added you to our links as recommended reading. If we can help you in any way do not hesitate to ask.

@CANanonymity we have an interesting scientific model for combination testing, we will publish this on the website once it is finished. The plan for us is to have all our data visible and accessible to all, we are a non profit and believe everyone should be able to engage with the work.

Why are there only 9 compounds? It is a good question and the answer is simple, visual impact on the website! We will be adding even more compounds as time goes on, we have over 80 compounds/dosages and referenced papers for them all. It is a question of testing things that are more useful first and hence Senolytics and Alk-5 (because there are no AGE breakers to test) seemed sensible.

You might like our first podcast on our youtube channel:

https://www.youtube.com/watch?v=rApmLWjvsjw

There will be more media coming shortly so keep an eye on us, we are negotiating with a third lab at the moment and hope to include a prominent rodent lifespan researcher in our lineup.

We also have social media:
Twitter: https://twitter.com/MajorMouseMMTP
https://www.facebook.com/groups/MajorMouseTestingProgram/

We are adding linkedin and Google+ media soon too over Christmas.

I will also add that we are indeed a mix of advocates and researchers and are keen to engage with people. We need help with all kinds of things including social media, longecity presence and more. If anyone wants to get involved drop us a line at info@majormouse.org

Posted by: Steve H at December 24th, 2015 5:02 AM

@Antonio I asked the same question about the Mprize. Our researcher Dr Stolzing said "we will use the money to fund more research and more testing to go faster" she is very much a pro-longevity researcher.

Noted on the grey text I was thinking this too.

We are going to announce a fundraiser in the new year and hope to work with lifespan.io and Longecity. We are not actively fundraising at this time though the donate button works and any donations will go into the pot for the funding launch.

We do indeed have costs for each test group though we are currently auditing costs to identify any savings we can make that are not at the expense of quality.

Posted by: Steve H at December 24th, 2015 5:07 AM

"we will use the money to fund more research and more testing to go faster"

Nice to hear that.

BTW, will each test be funded independently, or will there be only one crowdfunding for all?

Posted by: Antonio at December 24th, 2015 5:20 AM

@Antonio Well the plan is to have three labs working on this and that would be way too much for a single fundraiser. So we are dividing it into three labs/teams and will bring each online as situation allows.

An option for us is to add an additional test group as a stretch goal, this seems to be likely for the initial fundraiser.

If we make more funds than needed the excess will go into funding the additional labs so we ensure that if one lab is short and another is over funded they support each other. This will help us bring things online faster and doing things quicker (but well) is what we are all about.

We are looking at bulk testing of already known geroprotectors first but moving into combination work later. We should be publishing a novel research protocol for this once it is written so people can check it out.

We also communicate with the ITP and others too so we can move quicker.

Posted by: Steve H at December 24th, 2015 6:23 AM

@Steve H: I asked because maybe some people would prefer to fund the rapamycin test, others would prefer senolytics, etc.

Posted by: Antonio at December 24th, 2015 7:32 AM

@Antonio with Rapamycin all the labs will test it as it is to be our positive control group. This is to ensure we have consistent quality in all the labs.

Posted by: Steve H at December 24th, 2015 10:43 AM

@Nico yeah we are currently discussing a novel system for combination testing and Dr Miller is also involved in this and Josh. Things are looking very promising indeed for testing combos. We will publish a full protocol in due course.

I think we can make some real progress here and we will keep everyone updated. We are also playing with the website to make it better including the text colour.

If anyone wants to be involved drop us a line at info@majormouse.org we need all kinds of skills.

Merry Christmas to you all and I hope we can be a small part of bringing you all the best present of all!

Posted by: Steve H at December 24th, 2015 12:58 PM

Glad to hear that, Steve.

I think it's a fortunate circumstance that a mouse testing programme gets to meet and possibly implement enhancement proposals for mouse testing; that leads to a better use of financial resources, additional experiment excitement, and more chances for us all to enhance our lives in the long run.

I donated to MMTP yesterday and will donate again once you launch your wider crowdfunding campaign.

Happy holidays to all teams working hard cracking the ageing problem, and to longevity supporters supporting them :)

Posted by: Nico at December 24th, 2015 3:33 PM

Nico thank you so much!

I will keep everyone updated, we have lots of meetings coming up and much preparing to do before the fundraiser. We want to get this right so are pulling out all the stops.

We should announce our next researcher soon thanks to Michael Rae once again for his recommendations.

Posted by: Steve h at December 25th, 2015 5:30 AM

@Steve H Steve, can you tell me how you are involved with the medical research. You have written many times about activities in the mouse projects (and others?) and it would be nice to understand what you and your group are doing and organization you work for.

Also, I (and many others) are grateful of your involvement and also for providing status updates on the blog. I love hearing about progress being made.

Thanks Steve.

Robert C.

Posted by: Robert Church at December 25th, 2015 2:55 PM

@Robert

I am part of the volunteer team working for the MMTP, I am also in the ILA which the project is part of. I do various things in the group from helping source rodents, source drugs, help the researchers organise, admin the website and I am part of the MMTP social media team.

The project lead is Edouard one of the ILA board so suppose I am somewhat of a "man friday". There are a number of us working on the project ranging from advocates to full on researchers and everything in between.

We plan to do regular updates, interviews and all sorts as we believe keeping people informed and engaged should be the aim of science as well as the research itself.

Posted by: Steve H at December 25th, 2015 5:07 PM

Thanks Steve for your reply and info

Take care and thanks again for all you and your team are doing for all of us, Steve.

We appreciate the info you provide us via Reason's blog.

Robert C.

Posted by: Robert Church at December 26th, 2015 10:42 PM

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