$36,000
$25,176

An Interview with the Advocates of the Major Mouse Testing Program Team

By way of following on from today's AMA over at /r/futurology, I recently had the chance to ask a few questions of the Major Mouse Testing Program (MMTP) volunteers, a mix of scientists and advocates who aim to do their part to speed up progress towards effective treatments for the causes of aging. The group formed six months ago or so, and are presently seeking funds for their first mouse studies through crowdfunding with the Lifespan.io organization. The initial focus is on senolytic treatments capable of removing senescent cells from old tissues. I encourage you all to take a look at the details of their research proposal.

Growth in the number of dysfunctional, senescent cells is a contributing cause of degenerative aging, involved in the progression and pathology of all of the common age-related diseases. A growing body of evidence supports the outright removal approach as a way to minimize or eliminate this portion of the aging process. Unfortunately there is - as ever in the aging research field - a paucity of funding and always the need for more and better animal data in order to pull in other players with deep pockets. At this stage in the progression from laboratory to clinic, prior to the involvement of any large institutions or companies, all such efforts are important work. I'm pleased to have been able to contribute to this Major Mouse Testing Program fundraiser, and hope to see great things from this group in the future.

How did the Major Mouse Testing Program come about? How did you meet and what made you decide to undertake this particular project?

Elena: I have been collaborating with the International Longevity Alliance (ILA) for about 3 years. It is an international non-for-profit organization with the head office in Paris, our goal is to support innovative biomedical technologies to address aging. At the beginning, the core team had a lot of discussions with other pro-longevity organizations and with the scientific community to identify the bottlenecks that impede the development of the technologies to slow down, postpone and reverse age-related damage to health. And we learned that one of the barriers was the deficiency in robust animal trials for a long list of promising interventions. Then one of the Founding Board Members, Edouard Debonneuil, came in with the idea that the ILA could start its own fundraising project to support this kind of research. This is how MMTP was started.

Steve: I learned about the MMTP project via the International Longevity Alliance. They had a number of projects ranging from lobbying, advocacy to research, for me the research appealed as I wanted to get my hands dirty and get as close to the frontline as possible. MMTP is a mixture of advocacy and actual research so for me it was a good combination. The research is focused on speeding up progress in rejuvenation medicine so I felt it was important to get involved with this kind of project.

Paul: I learned about the MMTP project from Steve. He had just started working on the project, We knew each other quite well and had a good rapport, and he thought I'd be a good fit for the group. I wasn't initially keen to join the group, I didn't appreciate the work that animal researchers do, like a lot of people I guess I didn't appreciate why animal data is so important for developing new drugs and therapies. The more I learned about the project, the more I realised how vital the work was! My skillset seemed to fit the needs of the group so I decided to commit to the group.

The world would be a better place if everyone pitched in to move research forward. Why don't they? What are the challenges in doing this?

Elena: You would be surprised but there is a lot of studies in sociology that answer this question. As I am going to make my PhD in this field, I read a lot and I combine my own experience in longevity promotion with scientific evidence. So far, we know, that if you ask a person to choose a desirable lifespan, he or she will only add about 10 years to the mean life expectancy in any given country. But if you ask, if people would like to live longer while also remaining youthful and healthy, at least 30% will consent to live much longer or even indefinitely. Many people show more interest after being provided with the data from animal studies - which look fantastic today, with mice lifespan extended twofold.

Another important thing to keep in mind is that the perception of the innovation depends very much on its end use. People are keener to support a new and even experimental treatment for a severe disease, but often refuse to accept it in case it is used for life extension. Which basically means, that before promoting life extension technologies, we have to explain that aging is a root cause of severe age-related diseases, that aging itself is very similar to a disease, even if we don't call it so. If people can see how deteriorating aging processes are for their health, they will understand that it is only right to develop the means to protect people from its consequences. Cancer and diabetes are two of the most horrible consequences of aging, and I have not yet met someone who would say no to the development of a cure against cancer or diabetes. This is how powerful the admission of a serious problem can be.

Last but not least, we should not avoid talking about the prejudices and concerns that people have towards personal and social implications of longevity technologies. It is only reasonable that they want to make informed decisions. In our case, to be properly informed means to have some information outside the field of medicine. So we should share evidence-based data and expert foresight in demography, economy, ethics, ecology, law and other sciences on request, as in our case this is what can significantly influence public perception - and will also influence adherence to longevity therapies in the future. So, to get more supporters we seem to have a lot of educating to do.

Paul: Yes it would be truly amazing if more folk who declared an interest in this kind of research, actually played an active role in ensuring that it manifests itself as something people can go to a clinic and receive, rather than just daydreaming about it! But people are inclined to be either overly optimistic, or the complete opposite. Some don't believe this will ever amount to anything, so they see no value in joining the fight, and that is what this is. The other extreme, believe that it will happen whether they do anything or not, so why bother? They just sit around complaining about the lack of progress, while looking at exponential technology graphs, occasionally muttering "Are we there yet?" So the main challenge is to make people realise that this will not happen, if it is not made to happen. And if folks want this soon, it is in their best interests to pitch in and help get the job done.

You've been gearing up for your first fundraiser for a few months now; now that you're launched, what are the details?

Steve: We launched our fundraising campaign on lifespan.io with an ideal goal of $60,000 in order to initiate a robust scientific study. We will scale the experiment based on the funds we raise so no matter what, we will be making progress.

Elena: It is important to mention, that if we raise a little more, we will be able to do even more tests and so improve our data on health changes in our mice.

Once you have the funds in hand and are embarked on making mice live longer, what is next for the Major Mouse team?

Steve: Given the expertise of our researcher, we are very interested in moving into stem cell therapy for longevity. This could be very exciting as we plan to potentially combine senolytics with stem cell therapy. Imagine, first we remove the bad cells from the body, second - we stimulate the regeneration and replenish lost stem cells. This is one reason why our current study not only focuses on lifespan but our secondary goal is to closely examine the effect of senolytics on resident stem cell populations, this information will guide how we approach combining the two therapies.

Where do you see this field of rejuvenation research going over the next few years?

Steve: Stem cells are certainly shaping up to be a big player, CRISPR and gene therapy likewise. Senolytics has attracted a great deal of interest of late too though we need to robustly test this to ensure it is a viable path to longevity. There are a number of "camps" in the research community, the bulk seem to favour tinkering with the metabolism far downstream of the problems, another is the engineering strategy of SENS and the third is the hotly debated telomerase camp.

I think the most important thing at this point is to get the research underway, start answering the unanswered questions and work out what the best approaches are. Personally I see little value in messing with metabolism far downstream but which of the other two camps is right could be some of column A and some of column B. I am not married to either idea which is why we will test these things robustly and find out what works. It would be very poor science indeed if we made a conclusion and then cherry picked our results to support them, no we will research thoroughly and we will go where the data leads!

Elena: If anyone is expecting a universal pill against aging in the next 10 years, I don't believe this is going to happen. If you look at animal data, combine what they are treated with, then you can imagine, what a complex of anti-aging interventions is today. So far the approach to slow down and reverse aging includes drugs, senolytics, vaccines, cell therapies, gene therapies, organ regeneration in situ and of course lifestyle measures. In future, we will learn to combine several types of interventions in one procedure, and maybe we will wear a rechargeable bracelet able to inject a mix of longevity drugs directly into our bodies on demand, maybe several times a month. To repair a damaged organ we will have to undergo an injection of stem cells into that organ, which would supplant some of the more invasive interventions. By the way, this is what is already happening: an ongoing study in Melbourne, Australia, shows amazing results in joint repair in situ, on humans, using stem cell therapy.

Paul: Now that's a question! Things are moving so fast, every week there seem to be announcements, news about CRISPR and stem cells. These are two of the fastest moving areas of research. Those two and Senolytics, this is another rapidly accelerating area of research. Senolytics should help clear the senescent cells, and that will set the stage for recovery or rejuvenation. This is where things like stem cells come in. I know we would like to take our research into combination therapies, either combinations of the same therapies, involving multiple senolytics for example, or combinations of complementary therapies such as Senolytics and stem cells.

Funding is, obviously, ever the battle in the sciences, and especially aging. How can we change this for the better?

Elena: There are several ways for a scientific group to get funded. There is already settled state funding for the research - in this case, our goal is to make a state research institution more interested in investigating aging and longevity. There is an additional source - the grants. This is what most of gerontologists try to obtain, but this form of support has its own limitations: the paperwork can take too much time, there are some inconvenient regulations of spendings timeline, we hear many groups complaining about that.

Crowdfunding is much more attractive in this regards. We don't ask for excessive amount of papers, only a decent experiment protocol and a reasonable estimate, making clear the amount of such expenditures as the substances to test, the mice and their housing, and everything necessary to obtain the data on health changes. The contract between the ILA and the research institution guarantees the observation of the study design and volume. Apart from that, we let the scientific groups do their work without unnecessary distraction. Luckily, the cost of such experiments is from 60 to 100 thousand, so it can be acquired by crowdfunding. And while it is not so easy to influence state funds allocation, in MMTP we let general public influence the progress in biomedical sciences directly.

Paul: I think we need to educate interested parties at all levels, about the need to get this work done. About the potential, not only in terms of human lives and suffering that can be saved, but the enormous cost savings that could be potentially had too, by investing in preventative and rejuvenation therapies. Health providing organisations worldwide are creaking under the financial burden of established medicine, a model that offers increasing periods of decrepitude, in exchange for ever increasing amounts of money. This faustian bargain offers a very poor return on investment and simply cannot continue much longer. So advocacy and education are two of our biggest weapons going forward. We also need to foster a change in governmental policies worldwide! The ILA has already made a start, by approaching bodies like the World Health Organization (WHO), which themselves see a need for change. By the way, WHO recently held a Consultation on Global Strategy and Action Plan on Ageing and Health, where the need for more research on aging and longevity was discussed.

About the Team Members

Steve: Project lead for MMTP and a longevity advocate, whose energy and devotion is inspiring the team.

Elena: Project coordinator and fundraiser, Elena is involved in project management and community outreach to donors.

Paul: Social media manager and writer, Paul is an important part of our promotion team.

Comments

Thank you very much Reason for putting the info on your blog today.

The team members mentions Steve as Project Lead. Is this the same Steve who often makes comments about the MMTP on this blog? I assume so. I really appreciate his inputs on this blog.

Also, the total people are involved in this project is 3, correct? Where is this MMTP they located (Paris?), and do they expect to grow pending donations for the next project(s) (I.E. combinations treatments)

Thanks everyone at MMTP, I hope great success for these treatments/test/projects from MMTP.

Posted by: Robert Church at May 16th, 2016 7:35 PM

@Robert Church: More than three; these just happened to be the available three that day. You can see the full lineup at the MMTP site if you scroll down:

http://www.majormouse.org/?q=about

Posted by: Reason at May 16th, 2016 7:52 PM

This was a good AMA. The one thing that struck me as worrying though was when Elena was talking about the ICD-11 and how important it is that aging makes it in there. I know there were some promising talks earlier this year, and I'm hoping for the best on that end. But what's going to happen if it doesn't? Would something like senolytics only be used to a specific ailment (disease), instead of being prescribed for 'aging'? It would be a shame to have potential treatments that couldn't get approved for trial. The FDA gave the green light on the TAME trial, but what's the probability of there being more approved trials if aging can't get into ICD-11? I'm sure the FDA can do what it wants, but the classification by the WHO would obviously help out tremendously. Elena responded to me by saying she's optimistic on that end, but we'll see I suppose.

Other than that, I wish MMTP good luck on their tests.

Posted by: Ham at May 16th, 2016 7:58 PM

Thank you to everyone who joined us. It was not the biggest AMA in the world but considering we are a new project we were very pleased. We are monitoring the AMA thread still so additional questions may get answered over the next few days.

Posted by: Steve Hill at May 16th, 2016 8:34 PM

The skeptical part of my brain says that these are small molecule drugs, and could well have side effects at therapeutic doses in humans (despite being already approved drugs). I really hope that this fundraiser goes well and that the MMTP can then test some donated doses of Oisin Biotechnologies' "genetically targeted medicine" in a future crowd funded study.

Going on a bit of a tangent, I read this question "What is the status of your advanced glycation end products testing programme? Are there any promising molecules to test at all?"

I know from previous discussions on Fightaging.org that the major hold up on this may now be the lack of marker antibodies to glucosepane, and that these are being worked on in David Speigel's lab. But how much would it cost for the MMTP to try and produce some aptamers to glucosepane?

I'm asking about aptamers because I read an article on Nature.com some months ago about how they have been recently improved for in vivo use:
http://www.nature.com/articles/srep18478

I suppose the real question is - should the MMTP just be for lifespan studies in rodents, or should there be a few crowdfunding campaigns for tool development or basic research (other than by the SENSRF)?

Posted by: Jim at May 16th, 2016 10:01 PM

"Many people show more interest after being provided with the data from animal studies - which look fantastic today, with mice lifespan extended twofold."

What is the twofold extension Elena is referring to?

Posted by: Adam Spong at May 26th, 2016 3:37 AM

@Adam Spong: I'm not sure. Either she's rounding up the 70% life extension in GHRKO mice, or she's referring to one of the studies - such as those for rapamycin - carried out on very old mice that extends remaining life span, but I don't recall whether any of those managed a doubling of remaining time. I'd hope that I'd have noticed if that was the case.

Posted by: Reason at May 26th, 2016 4:49 AM

Googling the twofold phrase reveals an essay by Maria Konovalenko that refers to CR in Ames dwarfs achieving twofold extension. Given its prominence and similar wording, that might be the source. But it's a bit of an exaggeration. The raw data aren't available for the original Bartke study cited but the maximal lifespan extension relative to phenotypically normal (non-dwarf heterozygote) ad libs was about 50-60%. The Ames mutation alone extends lifespan by roughly half, but up to 70% in females on the right diet.
Here's the Ames CR survival curves
http://www.nature.com/nature/journal/v414/n6862/fig_tab/414412a0_F1.html#figure-title

Posted by: Adam Spong at May 26th, 2016 11:43 AM

EDIT to the above comment. The normals in the Ames CR study may have been bona fide wild types. (It's not stated in the brief communication, but the graph is labeled WT.) Most subsequent studies of Ames dwarfs compared dwarfs to phenotypically normal heterozygotes, derived from dwarf fathers and hetero mothers. But looking at the methods in Mattison et al., 2000 on Ames CR, the breeders were 2 heterozygotes and the wild types were studied.

http://www.ncbi.nlm.nih.gov/pubmed/23604794

Posted by: Adam Spong at May 26th, 2016 12:02 PM

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