A new paper coming out in Nature is getting a lot of attention, and well it should. This is some of the more dramatic anti-aging news that's been reported to date. (The accompanying editorial is also surely the first time anyone's quoted "Stairway to Heaven" in Nature).
The work hinges on a kinase enzyme called TOR (you often see an "m" in front of it, for "mammalian"). TOR, in accordance with the best gotta-name-it-something traditions of biochemistry, stands for "target of rapamycin", by which you would deduce (correctly) that rapamycin was discovered well before TOR. Rapamycin's a complex natural product first isolated from bacteria in a soil sample from Easter Island (Rapa Nui) - right here, in fact. In the late 1980s and early 1990s it was (along with another macrolide immunosuppresant, FK-506) the subject of a huge amount of research. (Note that FK-506 and rapamycin, though similar, still have some major differences in mechanism - unraveling these was most definitely nontrivial). Both compounds have strong immunosuppressive properties - the hope was that one or the other might prove to be some sort of universal transplant drug, among other things.
Rapamycin isn't that, but it's still useful, particularly in kidney transplants. And since TOR is involved in a lot of important cellular processes (brace yourself), inhibition of it by rapamycin and synthetic molecules has been studied extensively for other actions. The most interesting (well, perhaps until now) has been as an anticancer therapy. That alone illustrates the trickiness of this area, since one problem with any immunosuppressive therapy is a significantly higher risk of cancer. Decoupling these two effects has occupied a lot of time and effort over the years; that last link should give you an idea of the magnitude of the task.
But rapamycin has also shown life-extending properties in simple organisms, and this latest paper extends this effect to mice. The NIH group studying this had their problems, though - just adding the compound to rodent chow wasn't enough to achieve useful blood levels. More formulation work had to be done to produce an encapsulated version that could make it past the upper gut, and by the time that was worked out, the large cohort of mice set aside for the experiment was. . .well, rather more aged than planned.
But they went ahead with the experiment anyway, starting them off at 600 days old, which is roughly a 60-year-old human. Startlingly, the compound still extends life span, by about 14% in the female mice and 9% in the males. At ages where about 5% of the control mice were still alive, some 20% of the treated mice were still going. That's a very significant result, especially considering the late start. All in all, this looks like the most dramatic mid-to-later lifespan intervention that anyone's ever seen in a mammal. (Caloric restriction, for example, has been basically useless if started at the 600 day mark in mice, and no weight losses were seen here). There's a rapamycin study under way with mice in the prime of rodent life (starting at 270 days), and the preliminary results look quite similar (with again a stronger effect in the females).
The causes of death don't seem to have altered. A good sample of animals from both groups were checked by necropsy, and nothing significant was noted. That seems rather surprising, because the blood levels of the compound are (at least from what I can see) rather high. The paper mentions that the mice had 60 to 70 ng/mL rapamycin, and looking around, I find blood levels of 15 ng/mL mentioned as effective in tumor suppression in one mouse model, and the immunosuppressive doses seem to be similar. I'd be glad to hear from anyone who knows more about rapamycin dosing in mice, though; it's definitely outside my range of experience.
Are people going to run out and start taking the stuff? It wouldn't surprise me, although I'd have to say that that's a bad idea at the moment. There's an awful lot that we don't understand about the tradeoffs between aging, cancer, and the immune response, and I'd hate to end up on the wrong side of that bet. Jumping straight to humans is too big a leap for now, but remember - there are a lot of other mTOR inhibitors out there in development (try this paper for starters). If we can narrow down which pathways are important for lifespan (and believe me, there are people thinking hard about this right now, especially after this paper), then there could be some very interesting opportunities