Hypothesis Volume 2, Issue 8 pp 461—470

Figure 1. Lithocholic acid (LCA) extends longevity of chronologically aging yeast through two different mechanisms. (A and B) Outline of pro- and anti-aging processes that are controlled by the TOR and/or cAMP/PKA signaling pathways and are modulated by LCA in yeast cells grown under non-CR (A) or CR (B) conditions. Activation arrows and inhibition bars denote pro-aging (displayed in green color) or anti-aging (displayed in red color) processes. Under both non-CR and CR conditions, LCA targets housekeeping longevity assurance processes listed in (C). Under non-CR conditions only, LCA also targets the adaptable cAMP/PKA pathway. By activating PKA-dependent phosphorylation of the cytosolic pool of the key nutrient-sensory protein kinase Rim15p, LCA causes the inactivation of Rim15p. The resulting reduction of the phosphorylation status of several Rim15p target proteins in the cytosol lowers their pro-aging efficacy. Abbreviations: CR, caloric restriction; PM, plasma membrane.