The finding reported in this study, that the enhanced activity of G3PP and of the glycerol shunt leads to constitutive activation of AMPK, TFEB, and autophagy, three key evolutionarily conserved longevity-promoting factors, sheds light on an unexplored role of G3PP and the glycerol shunt in the protection against aging-associated diseases and the promotion of healthy aging in disease contexts such as metabolic disorders associated with nutrient excess, atherosclerosis, and neurodegenerative disorders. Here, TFEB is linked to metabolic disease.