Michael Rae (of the CR Society) penned an informative post on calorie restriction (CR) research at the Immortality Institute today:
One of the most distinct effects of CR is the lowering of integrated insulin and glucose levels, and it's widely believeed that one or the other or both play major roles in the anti-aging action of CR. To test this, one wants to be able to manipulate one or the other or both, without lowering Caloric intake.
Famed CR and exercise researcher Roger McCarter has been doing some work with transgenic (TG) animals that overexpress the gene for GLUT4, the main glucose transporter in skeletal muscle. Basically, when insulin stimulates muscle, there is a cascade of molecular events which move GLUT4 to the cell surface, where they engulf glucose at the plasma and move it into the cell. By making more GLUT4, these mice suck up more glucose. Somewhat surprisingly, their insulin levels don't go down in homeostatic adjustment: they just have lower circulating glucose levels (and thus, presumably, fewer extracellular [advanced glycation end products]).
One of the many exciting things on which you missed out if you didn't come out to the CR Society 2004 Conference was McCarter's old coinvestigator, Ed Masoro, informing us that McCarter has found that these GLUT4 transgenics have no changes in their lifespan. This suggests that, at a minimum, low glucose levels per se -- and extracellular AGE -- are not the *primary* mechanism of CR's anti-aging action, and may conceivably not contribute to it at all.
Now, in results presented at the 2004 Gerontological Society of America meeting, they report that the lower glucose level does not appear to effect (OR affect!) CR-associated gene expression changes.
The interesting science continues to roll in for calorie restriction - a sign that decoding the puzzle and the ensuing production of CR mimetic therapies for healthy life extension cannot be too many years in the future. In the meanwhile, there's nothing stopping you from investigating calorie restriction the old fashioned way. Why wait years for treatments when you can get started on at least modestly extending your healthy life span right now?