Numerous sources like this say that rapamycin increases lifespan. And mTOR antagonism appears to be a large part of this (mTOR antagonism also appears to be a large part of calorie restriction's mechanism too).

Is the effect of calorie restriction equal to that of rapamycin treatment or are there differences?

  • $\begingroup$ I included the actual question in the main text, as it was not immediately clear what was the point of the question (I had to go back and re-read the title and then I understood). $\endgroup$ – nico Mar 11 '12 at 13:03

Rapamycin specifically inhibits the mTOR pathway (mTOR = mammalian target of rapamycin), which has numerous downstream functions including protein biogenesis, regulation of cell cycle, immune function and apoptosis. The upstream effectors of mTOR include growth factors and amino acid availability, so you can certainly see that the lifespan enhancing effects of caloric restriction will be (at least in part) mediated by the mTOR pathway.

But there are key differences. mTOR also receives signals relating to DNA damage and inflammatory changes (to name just 2) that are essential for healthy survival. So any direct inhibition of this pathway will affect all the functions - I can't find the reference now, but I have definitel read in one of the numerous rodent studies that rapamycin treated mice have reduced immune function (i.e. the lifespan increased effects can only be seen in a controlled lab environment - in the wild mTOR-inhibition to this degree would be a disadvantage).

I think therefore it is fair to say that the effects of caloric restriction on longevity are mediated by mTOR, but administration of rapamycin is not an equivalent treatment.


Really great review came out last month (http://www.ncbi.nlm.nih.gov/pubmed/22500797) - I recommend you give that a skim if you want detail!

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    $\begingroup$ Please add some sources... $\endgroup$ – nico Apr 13 '12 at 16:22
  • $\begingroup$ @inquilinekea - It is important to note that 'caloric restriction' is not actually a single process - there are different types (e.g. 'diluted' food, or alternatively eating every other day) that are mediated by distinct molecular mechanisms - some of which are mTOR, others may be IGF/insulin signaling (these effects are additive!) [Greer et al (2009) Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans] $\endgroup$ – Luke Apr 25 '12 at 10:43

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