Breathing lessons: Tor tackles the mitochondria

issue of Aging further extends our understanding of the growing connection between the TOR pathway and mitochondrial function [1]. Interest in the TOR pathway for the aging community was initially spurred by a flurry of reports suggesting that in various model organisms, inhibition of this pathway could trigger lifespan extension [2-5]. In yeast, the TOR pathway regulates a number of diverse biological outcomes. For instance, treatment of S. cerevisiae with rapamycin, a highly specific TOR inhibitor, triggers cell cycle arrest, glycogen accumulation, increased autophagy, a global reduction in protein synthesis and sporulation. Adding to the complexity are the observations that in yeast as well as in mammalian cells, the TOR kinase exists in two separate multiprotein complexes. These complexes designated TORC1 and TORC2 have different biological functions as well as different sensitivities to agents such as rapamycin. Further complicating the matter, in mammals there is a single TOR gene that functions in both the TORC1 and TORC2 complexes, while in S. cerevisiae there are two distinct TOR kinase genes. How does a reduction in TOR signaling lead to lifespan extension? Most evidence suggests that the TOR pathway is intimately linked to the sensing of nutrient status. In a simplified sense, TOR signaling is active when nutrients are abundant and inhibited during periods when food is scarce. Such observations have suggested a potential link between TOR activity and other well know strategies such as caloric restriction wherein limited food availability results in lifespan extension. While such links are on one level satisfying, the exact molecular connection between TOR activity and lifespan remains incompletely understood. It is in This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited this context that the work of the Shadel laboratory is quite illuminating [1,6]. As mentioned above, yeast have two TOR kinase genes. While Tor2p deletion is lethal, yeast without Tor1p are viable. Interestingly, these tor1Δ yeast strains are not only capable of surviving but actually have an increased chronological lifespan. Others have also observed that in yeast a decrease in TOR signaling resulted in lifespan extension, although these previous studies have implicated alterations in the stress resistance as the cause of this lifespan extension (5). In contrast, Shadel and colleagues have previously provided evidence that the increase in chronological life span …