A model for nutrient signaling, acetate-dependent acetyl-CoA synthesis, epigenetic modifications, autophagy, and longevity. In yeast acetyl-CoA is produced through the mitochondrial pathways (Ach1 or Mpc1 dependent) and through the Acs2-dependent nucleo-cytoplasmic pathway. The hyper-activation of the Acs2-pathway by high levels of acetate results in increased levels of nucleo-cytoplasmic acetyl-CoA, which, in turn, leads to hyperacetylation of histones, reduced expression of ATG genes, autophagy inhibition, and shortened lifespan. However, relatively high levels of ketone bodies are associated with longevity extension in mutants lacking Tor-Sch9 or Ras-PKA signaling, indicating that, similarly to ketone bodies, this carbon source can promote either toxic or protective effects depending on the signaling state of cell. In this model, solid arrows indicate known pathways while dashed arrows indicate putative pathways based on current knowledge.