GATA transcription factors (TFs) are a conserved family of zinc-finger TFs that fulfill diverse functions across eukaryotes. Accumulating evidence suggests that GATA TFs also play a role in lifespan regulation. In a recent study, we have identified a natural compound, 4,4' dimethoxychalcone (DMC) that extends lifespan depending on reduced activity of distinct GATA TFs. Prolonged lifespan by DMC treatment depends on autophagy, a protective cellular self-cleaning mechanism. In yeast, DMC reduces the activity of the GATA TF Gln3 and, at the same time, deletion of GLN3 increases autophagy levels during cellular aging per se. Here, we examine current data on the involvement of GATA TFs in the regulation of both autophagy and lifespan in different organisms and explore, if GATA TFs are suitable targets for anti-aging interventions.