Moreover, many studies have reported that lifespan extension induced by CR is associated with the down-regulation of mTOR activity [108,111]. Harrison et al. [79] observed that rapamycin, a recognized inhibitor of mTOR, could extend lifespan in mice if fed late in their life. Recently, Anisimov et al. [112] demonstrated that the lifelong administration of rapamycin extended lifespan in inbred female mice. Moreover, rapamycin could also increase maximal lifespan in cancer-prone mice [113]. Cao et al. [114] observed that rapamycin treatment reversed the senescent phenotype of Hutchinson-Gilford progeria cells in culture by stimulating autophagy. Rapamycin treatment has also been reported to be able to reduce age-related cognitive defects. Majumder et al. [115] demonstrated that life-long administration of rapamycin improved the spatial learning and memory performance in aging mice. Interestingly, this was associated with a decrease in the brain level of IL-1β but not that of TNF-α which could be interpreted to imply that the inflammasomal activity had been reduced by rapamycin therapy. This suggestion is in agreement with the results of Mawhinney et al. [116] which indicated that increased inflammasome activation was linked to age-related cognitive impairment in rats. Rapamycin, also called sirolimus in clinical use, has been intensively studied as
