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December 09, 2011

Getting the Life Extension benefits of Rapamycin without the Side effects

In a recent issue of Cell Cycle Anisimov and et al. reported that lifelong intermittent administration (three times a week for 2 weeks, followed by a 2 week break) of rapamycin started at 2 months of age (in mice) significantly increased maximal lifespan and delayed spontaneous cancer in normal inbread female 129/Sv mice. This study is in agreement with the effect of inhibition of Tor/S6K signaling in protecting yeast against age-dependent DNA mutations and of mutations in GH or GHR in reducing cancer incidence in mice and humans. Similarly, dietary restriction (calorie restriction) without malnutrition extends lifespan and powerfully protects against cancer in mice.

Intermittent dosage of Rapamycin extends maximum and average lifespan and reduces cancer (similar to the effects of calorie restricted dieting) with what should be reduced side effects in mice. More work on mice and monkeys is needed, but this could be a way to get Rapamycin used to mimic calorie restriction benefits of life extension and health improvement to humans in a few years.




Rapamycin is an immunosuppressant and antiproliferative agent that is clinically used to prevent rejection in organ transplantation, primarily in renal transplant patients. Rapamycin by inhibiting the activation of mTORC1, inhibits effector T-cell proliferation and dendritic cell maturation, but does not supress TReg cells induction. Data from experimental studies indicate that rapamacyin prolongs allograft survival and reverses acute rejection of kidney allografts in in rodents and humans. Besides the well-known immunosuppressive and anti-rejection properties of rapamycin, there is accumulating scientific evidence supporting a potential anti-atherogenic, anti-fibrotic, antiangiogenic, and anticancer effect of rapamycin. Nevertheless, chronic subministration of rapamycin is associated with a number of side effects in some renal transplant patients, including impaired wound-healing, lymphoceles, delayed graft function, anemia, pneumonitis, hypercholesterolemia and proteinuria. However, these side effects are dose-dependent, and it is not known if lower doses and intermittent subministration may limit some of these effects and potentiate the beneficial effects. Interestingly in this paper rapamycin was able to extend lifespan and reduce cancer risk in mice also when used with an intermittent schedule. More studies are needed to understand benefits and side-effects of rapamycin supplementation in different strains of mice and in monkeys as a candidate cancer-preventive and life-extension pharmacological agent. However, the efficacy of intermittent rapamycin treatment in cancer prevention and life span extension shown by Anisimov et al. is very promising since it is likely to reduce the side effects associated with chronic treatment.

In fact, dietary restriction (DR), a reduction in food intake without malnutrition, lowers Tor/S6K signaling and extends the average and maximum life span of a variety of organisms including yeast, flies, worms, fish, and rodents. In both rodents and monkeys, it delays loss of function and reduces the incidence of major diseases and in humans it causes a reduction in several metabolic factors and markers of diseases associated with including diabetes, and cardiovascular disease and cancer

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