Fight Aging!

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.