Here we showed that the caloric restriction mimetic (CRM) 3,4-DC is a potent inducer of autophagy in cardiovascular disease-relevant cell types, it is bioavailable after intraperitoneal injection (as well as upon topical application) and can be used for the prevention of atherosclerosis in two rather different mouse models, (i) neointima formation in vein segments grafted to the carotid artery and (ii) genetically predisposed ApoE−/− mice fed an atherogenic diet. The gene discussed is APOE; the disease is atherosclerosis.