Suggesting a Test of Rapamycin and Metformin Together

Rapamycin extends life in mice through mechanisms similar to those of calorie restriction, but has serious side-effects - though researchers are working to separate the positive mechanisms from the undesirable negative mechanisms. Metformin is also thought to be a calorie restriction mimetic drug, but the evidence for it to extend life in mice is mixed. Here, researchers suggest trying both drugs at the same time in the hopes that metformin blunts some of the side-effects of rapamycin: "Treatment with rapamycin, an inhibitor of mammalian target of rapamycin complex 1 (mTORC1) can increase mammalian life span. However, extended treatment with rapamycin results in increased hepatic gluconeogenesis concomitant with glucose and insulin insensitivity through inhibition of mTOR complex 2 (C2). Genetic studies show that increased life span associated with mTORC1 inhibition can be at least partially decoupled from increased gluconeogenesis associated with mTORC2 inhibition. Adenosine monophosphate kinase (AMPK) agonists such as metformin, which inhibits gluconeogenesis, [might] be expected to block the glucose dysmetabolism mediated by rapamycin."



Good suggestion.
Since caffeine is also an AMPK agonist -

"Caffeine Enhances Endothelial Repair by an AMPK-Dependent Mechanism"

- it may be work synergistically with rapamycin also.
Besides, caffeine also inhibits mTOR.
Would adding an nf-kappab inhibitor increase longevity even more?

Posted by: Lou Pagnucco at July 5th, 2012 8:41 AM

How does does the combination of metformin with rapamycin affect metformin's efficacy as a diabetes medication?

Posted by: Phil at July 6th, 2012 11:21 AM

I have been on 2000mg per day of metformin for 15 years and I do not have any problems with insulin sensitivity, although I am a type I diabetic.
Metformin reduces my insulin requirements by about 20%, which I think is
great. I started on rapamycin about a month ago, so I guess I'm in a study group of one. Heck I drink an entire pot of coffee everyday, too. I've had diabetes for 26 years without any complications, so something is working.

Posted by: Mike Burns at July 9th, 2012 7:42 AM
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