Figure 8. Model of How TOR Signaling and CR Regulate Yeast Replicative Lifespan.

CR and TOR signaling regulate the nuclear localization of Msn2p/4p. When localized to the nucleus, Msn2p/4p promote the transcription of PNC1, a nicotinamidase. The removal of NAM by Pnc1p increases the activity of sirtuins, including Sir2p and Hst2p, which promote longevity by stabilizing the yeast rDNA array and preventing the formation of ERCs. TOR signaling may also regulate lifespan by sirtuin-independent pathways, such as the regulation of ribosomal biogenesis.