Figure 1: Conserved longevity pathways and processes, which modulate aging via autophagy. Additional interventions not listed here, e.g., the polyamine spermidine may also engage autophagy as a possible effector mechanism to extend lifespan. For simplicity, the interactions between the pathways are not shown, whereas the degree of conservation is indicated. Whereas the mechanisms by which autophagy affects aging through these longevity paradigms are not yet fully elucidated, several positive regulators of autophagy have been identified, including the forkhead transcription factor FOXO (nsulin/IGF-1 pathway, mammals), the histone deacetylase SIRT1 (dietary restriction, mammals), the energy sensor AMPK (insulin/IGF-1 signaling and dietary restriction, mammals and worms), and the forkhead transcription factor PHA-4/FOXA (dietary restriction and germline removal, worms).