Figure 1. Two distinct models whereby p66shc may integrate ROS and the TOR/S6K cascade in the aging process.

(A) ROS upregulate p66shc and activate S6K through p66. Oxidant species could be generated by mitochondria in response to nutirents, thus creating an alternative route for nutrient sensing by S6K. (B) S6K, activated by p66, increases ROS formation in mitochondria. In this case p66 could be in turn activated by cellular stress, by p53, or by environmental oxidants. In both examples p66 effects on aging are inhibited by calorie restriction (green box) that reduces nutrient supply. Activation" of p66shc is depicted as a result of increased expression (larger icon) and serine phophorylation (letter "P"). Both changes have in fact been reported in response to diverse stresses in mammalian cells.