The ITP (Intervention Testing Program) is the gold standard for testing longevity interventions in mice. Of 69 tested ITP interventions these are the 10 best max lifespan interventions in male mice.
Will post next week the female edition here.
Great stuff Krister! Thanks for posting.
One small commentā¦ I think the āmax lifespanā youāre quoting is the max lifespan increase in the last 10% of surviving mice (that they use in the ITP program statistics) - and not the absolute largest Max Lifespan of the last remaining mouse. You may want to have a footnote at the bottom to clarify this information, but perhaps its not needed. Your call.
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Thanks.
I am waiting for a Canaglflozin + rapamycin study.
Have I missed something?
I now take Canagliflozin instead of metformin and I couldnāt abide the side effects of acarbose.
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The size of the image is very optimize currently so hard to fit more information to it as footnote. But as I have interpreted it when researchers report max lifespan itās in most cases the value for the 90% quantile which is reported and not the absolute largest max lifespan of a single subject in a study. One reason for this is to avoid cases where a single subject was for example borned with some kind of super genetics which has nothing to do with the intervention which is tested. So I would say best practices is max lifespan is 90% quantile if nothing else is said. But I agree that itās good to try to be as clear as possible.
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One way of pushing that intervention forward is to send in a proposal to the ITP regarding testing that combo. My plan is to send in a proposal so that they test everolimus so that we get important data if itās better in extending lifespan in mice or not than rapamycin.
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This is the female edition of the best 10 ITP longevity interventions in mice (sorted by max lifespan). A big difference with the male edition is that in all the best female interventions rapamycin is involved in.
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Itās obvious from these that Rapamycin + Acarbose (or Metformin) is quite synergistic. Iām glad weāve identified it. What other interventions can synergistically improve these results?
Reminds me of these twitter posts:
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Very good that you lift this up. I had a talked with the researcher Pankaj Kapahi last week and he also talked little bit about this that too much of a good thing can be detrimental and that interventions needs most likely to be more adapted to the specific individual. There is no one size shoe that fits all.
But I think there may be some interesting potential synergistics in keeping glucose and insulin levels from peaking. Like for example when combining Rapamycin with Acarbose. The big problem is that we donāt know the optimal dose regime of Rapamycin and when we on top of that start to add Acarbose things get even more complicated on what the optimal dose regime of those two together are. But I think science points to that there may be something promising in combining mTOR inhibition and glucose regulation.
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I think it is pretty obvious that Rapamycin needs to have some sort of glucose support from either Metformin or Acarbose or both. The ITP results make this pretty apparent. However, what do you add to that to make it even better? Probably something to counter the increased triglycerides.
I am not sure what is going on with my biology, but ever since I have started taking Acarbose, I feel like I am constantly āOnā. The energy is amazing and more than I have felt even in my youth. Maybe itās the weight loss?
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In mice also calorie restriction seems to have some additive effects.
Here is an study on flies which show that the combination of Rapamycin and downregulation of IIS can have benefits
Here is another triple combination of compounds (Rapamycin + Lithium + Trametinib) in flies
But these are animal studies so we need more research to see how effective they translate to humans.
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Very interestin about seing if there are any synergie effects with something that keeps lipid in good levels. Let me know if you find anything in the topic.
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It just makes sense to me because we know the two downsides to Rapamycin are increased blood sugar levels and increased triglycerides. By addressing the blood sugar levels, life expectancy goes up. It makes sense that the same would hold true for triglycerides. This should be something the ITP tests.
Actually, a lot of us are already doing this in our own practice.
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One good question to ask here is also if a person will not have any problems with blood sugar or lipid levels will there be synergie effects even in these cases or will it be to push things too far.
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That makes a strong case for Lithium, which I do microdose. Trametinib seems to be a chemotherapy agent that also extends life expectancy. It seems to be more effective than Rapamycin? Maybe the ITP should test it? @invivo
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One of the problems is that a lot of animals, including rats, do generally not suffer from cardiovascular disease to the extreme extent that humans do (the largest killer of humans in the developed world).
On the one hand, that may mean that your point about it being important for humans to address increased lipids from rapa (via diet, excise and and/or pharmaceuticals) is even more crucial for someone seeking to extend their health and life span.
On the other hand, I means that we may need data from outside of rodents (and the ITP) to better understand the value of addressing lipids via interventions when taking rapa.
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Rapamycin 42 ppm started at 20 months of age show a 11 % extension of median lifespan in male mice.
Rapamycin 14 ppm started at 20 months of age show a 20 % extension of median lifespan in male mice.
Rapamycin 14.7 ppm in combination with acarbose started at 16 months of age show a 14% extension of male median lifespan.
When rapamycin alone, is started later in life, then a low dose give better results. Can we, in a meanigful way, translate this approach to humans? How do the forum interpret these data?
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Is that ITP data?
Do you have the source to where you got those numbers 
Its quite difficult really because the mouseās metabolism is quite different. I think perhaps the key thing is that there are circumstances where the sweet spot is a lower dose than an alternative dose that still has some merit.
As people know I think it is worth having mTOR uninhibited the majority of time, but having periods dedicated to autophagy and there some inhibition of mTOR is useful.
I wrote a page following attending the UK Autophagy Network
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