The hammer of TORC1!

permits unrestricted nonommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. Explaining aging in evolutionary terms is relatively simple: while a strong selection pressure for an indi-vidual's survival exists until the per-petuation of his progeny is secured, there cannot be selection of characters improving survival and life quality beyond this point. This evolutionary perspective lights the (long) path to increased lifespan, saying: " reproduce later! " or " remain of use to your kids as you get older! " but it leaves aging mechanisms thoroughly unexplained. Unfortunately understanding how we age proves more difficult. In 1990, ZA Medvedev listed more than 300 competing models for aging. Among them the mito-chondrial free radicals theory was perceived as the most promising. It suggests a vicious circle of damages: reactive oxygen species (ROS) naturally produced by the respiratory chain cause mitochondrial DNA mutations which in turn increases ROS production by the respiratory chain. This theory stood until the mid-2000's when A Trifunovic released her study of the " mutator " mice. Mutator mice present most, if not all signs of premature aging associated with the accumulation of mitochondrial DNA damages and respiratory chain deficiencies but show no sign of ROS accumulation. 1 In a recent publication Scialo et al. provide evidence in favor of a different aging paradigm. 2 Drosophila melanogaster, popularly known as fruit flies, are poikilothermic animals. Instead of maintaining their own body temperature like humans, they let ambient temperature control their physiology, metabolism and lifespan. Taking advantage of this behavior Scialo et al. studied the trade-offs associated with thermic adaptation. Lifespan shows non-linear correlation with temperature , presenting optimal survival at 18 C (Fig. 1, insert), a " normal " temperature for fruit flies. The authors observed that most parameters they studied including ROS and various metabolic markers evolve with temperature but not with lifespan; whereas TORC1 and Akt signaling correlate negatively with longevity. Effectors downstream of TORC1 did show the Figure 1: Left insert; Lifespan correlates with TORC1 signaling but not with metabolism (or ROS) in Drosoph-ila exposed to different environmental temperature; adapted from. 2 Pathways map: crosstalk between the various signaling pathways controlling TORC1. Proteins downregulated in Scialo's study when lifespan increases are in green boxes, orange boxes delineates proteins unconnected to lifespan. For the sake of clarity several intermediates of the …