Mouse testing program: search for new interventions to increase lifespan
Mouse will help people to live longer
Among priorities we found an obvious common one: funding a major mouse testing program (large series of mouse lifespan tests, starting with aged mice; including health markers as well and including combinations of interventions).
Intrigued? Below is an FAQ, including how you can help.
WHY SHOULD I BOTHER?
We believe that mice are the best test subjects and this research will lead us to longevity therapeutics. The goal of the project is to discover a sufficiently large and varied base of robust mouse geroprotectors, in order to “connect the dots” in the research and to make human lifespan extension a reality.
ISN'T IT DONE ALREADY?
Robust mouse healthspan and lifespan models have been developped and are being used by the great pioneers in longevity research, most famously at the Intervention Testing Program. This makes such a project possible now. However at the current pace, if about 5% of tested interventions lead to statistically significant life extensions, then a robust set of 100 geroprotectors will be found in maybe a hundred years! Too late for you? Our goal is to accelerate this by a factor of 10 to 20 times by running a few consecutive series of MANY lifespan tests in parallel
WILL INTERVENTIONS BE COMPOUNDS OR GENE THERAPIES?
Possibly both and maybe more. We believe that geroprotecting drugs are likely to bring the first human applications, given the knowledge about risks we already have (e.g. with metformin and punctual, low dose anti-inflammatory drugs). However gene therapies are being developped for various diseases as well as age-related diseases today and could likely be more efficient and non-toxic.
WILL YOU TEST COMBINATIONS?
Adjusting doses and combinations is at the very heart of the project. Today, it is possible to double the lifespan of laboratory mice by combining genetics and caloric restriction.
WILL INTERVENTIONS START WITH YOUNG OR AGED MICE?
We will start with relatively aged mice (16-18 months of age), given better translational opportunities to extend healthspan and lifespan in aging populations. Positive findings will then be tested starting at younger ages.
HOW MANY SERIES SHOULD BE PERFORMED? HOW MUCH TIME WILL IT TAKE?
Interventions will be well selected, a first series will hightlight various life extensions. Following each series, positive life extensions will be tested again, alone and in combinations. In the case of compounds, detrimental interventions will be tested with lower doses, positive and neutral life extensions will be repeated with an increased dose (depending on what has been tested again). With such a procedure, we think that after three series -- perhaps four -- there should already be a large set of large and robust life extensions found. Starting with aged animals allowing for shorter consecutive experiments, within 6 to 8 years
WILL IT BE TRIPLICATE, INDEPENDENT, BLIND STUDIES?
Studies will be repeated as described above. Positive results will be verified in different places. Studies will be blind where possible (in addition performing numerous tests in parallel should reduce such bias as well as ease the attention paid to details that count for the overall project).
MUCH ABOUT LONGEVITY... WHAT ABOUT HEALTH?
Health markers will be assessed in addition to longevity. The concept is to address aging processes and associated damage, rather than specific diseases, therefore longevity being a side effect of a longer health. In addition to general health, the project is likely to also lead to a number of treatments for specific age-related diseases.
I BELIEVE THAT GETTING RID OF SENESCENT CELLS/REACTIVATING STEM CELLS/OTHER IS THE BEST WAY TO FIGHT AGING AND AGE-RELATED DISEASES. SHOULDN'T WE FOCUS ON IT INSTEAD?
If your intuition is correct, many things that will extend lifespan should help the body get rid of senescent cells/reactivate stem cells/other. Based on current knowledge, it might be difficult to choosing an intervention that does what you are looking at; and more over the intervention's benefits could be masked by known-or-not-known side effects. Therefore that way of addressing aging should be efficient.
WHY NOT FOCUS ON C ELEGANS? WHY NOT FOCUS ON PEOPLE?
After large life-extension screenings in c elegans, where about 10% of interventions extended lifespan by at least 10%, researchers gradually found a way to extend their lifespan by much more, close to ten fold.
While some results do apply to mice, it is clearly not systematic. Mice are not c elegans and do not appear to age and die for the same reasons. In particular, c elegans have a fixed number of cells at adulthood, making cell resistance particularly useful, and no issues with cancers.
Mice are not humans but both are mammals so there is a hope for better translations between the two species, such as we have seen with drugs. One of the strategies for mammalians to live long is to regrow tissues continuously, without adhering to a fixed number of cells.
Humans may already be under natural geroprotectors effects but such investigation is much more complex in terms of time and costs.
HOW MUCH WILL IT COST?
Full cost is close to 100$ per mouse per year; if the goal is to reach at least 100 geroprotectors, tested at various doses and with at least one combination therapy and if we can assume that 5%-7% of interventions are found to be geroprotective this leads to a total cost for the project being around $30 million. This is tight, without much security margin. Smaller amounts of funding will lead to fewer discoveries and larger funding will lead to more discoveries.
HOW CAN I HELP?
If you are knowledgeable or have access to knowledgeable people about a specific compound/intervention and have a view on what dose/protocol should be tested on lifespan, please contact us. If you can or you know someone who can financially contribute to longer and healthier lives, please contact us! A transparent and official funding structure is currently being set up.
Project leader: Edouard Debonneuil, member of the Board of founders of the International Longevity Alliance
Languages: English, French
If you want to contribute to the promotion of longevity technologies, we would be glad to have you in the project team. Please contact the project leader by e-mail or fill in the Supporter Questionnaire!