As Cuervo [67] outlined, the role of autophagy is to “keep that old broom working” with aging. As discussed above, there is much evidence that caloric restriction can activate autophagy and also extend lifespan, probably via its beneficial health effects. Currently, there are a number of drug discovery programs aimed at finding safe chemicals which would be able to activate autophagy. There are two potential groups of compounds acting in this way; mTOR inhibitors [103,104] and AMPK activators [105,106] (Figure 1). mTOR is the major inhibitor of autophagy and is involved in aging [107,108]. Rapamycin and other mTOR inhibitors are either used or under investigation for therapy of cancer and many age-related diseases [107-110]. mTOR is a key protein kinase which couples nutritional and growth factor signaling to protein synthesis, transcription and critical responses in cellular growth, proliferation and survival. 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
