Suggesting a Test of Rapamycin and Metformin Together
Permalink | View Comments (4) | Post Comment | | Posted by Reason

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."

Link: http://dx.doi.org/10.1089/rej.2012.1347

Comments

Good suggestion.
Since caffeine is also an AMPK agonist -

"Caffeine Enhances Endothelial Repair by an AMPK-Dependent Mechanism"
http://atvb.ahajournals.org/content/28/11/1967.full.pdf

- 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 5, 2012 8:41 AM

Also worth noting is that metformin may promote brain health by increasing neurogenesis. See:

"Diabetes drug triggers neuron growth, potential to regenerate brain cells: study"

http://www.stemcellcafe.com/stem-cells/diabetes-drug-triggers-neuron-growth-potential-to-regenerate-brain-cells-study.php

Posted by: Lou Pagnucco at July 6, 2012 10:39 AM

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

Posted by: Phil at July 6, 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 9, 2012 7:42 AM
Post a comment; thoughtful, considered opinions are valued. Please note that comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.









Remember personal info?