From what I know some combinations can cancel each other:
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- AKG and berberine alone extends lifespan in mice but AKG + berberine give 0% lifespan extension.
Brian Kennedy said “we had problems picking good combinations” - but I can’t find any other bad combinations that they were testing
- AKG and berberine alone extends lifespan in mice but AKG + berberine give 0% lifespan extension.
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- Metformin and Rifampicin increase lifespan at C Elegans individually by 20% but combined they extend lifespan by 5%
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- FGF-21 and Klotho gene therapies alone in mice improved kidney and liver function but combined they were worse than placebo
Probable explanations:
- Maybe Berberine increases AKG itself, so organism have too much AKG?
- Maybe Rifampicin increases Metformin blood level and makes it toxic? (Metformin increases lifespan only at ideal dose - 70% higher Metformin dose and it is toxic (with Rapamycin dose can be 3x higher or lower than ideal and it still works))
- FGF-21 and Klotho have very similar functionality - so combining them is bad
On the other hand, some combinations that are positive:
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- Rapamycin + Acarbose in mice (especially in male mice)
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- Glycine + NAC - has 20% effect in mice lifespan - but not confirmed by NIA ITP yet - both Glycine and NAC extends lifespan in mice alone by about 5%
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- Rapamycin + Lithium + Trametinib - in Drosophila each compound extended lifespan alone by 13%, when combined it was 45% lifespan extension (probably the most in Drosophila beyond genetic manipulations)
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- Rapamycin + Rifampicin + Allantoin - each extended lifespan in C Elegans by about 20% - combined they gave about 60% life extension (the most so far beyond genetic manipulations)
