Macroautophagy is a process that sequesters and degrades organelles and macromolecular constituents of cytoplasm for cellular restructuring and repair, and as a source of nutrients for metabolic use in early starvation. Extensive evidence has been reported that macroautophagy process declines with increasing age. This impairment, probably due to ad libitum feeding, may cause accumulation of altered structures leading to the age-related decline in cell functions. It has been suggested that caloric restriction (CR) and disruption of insulin-like signals contrast the process of aging by prolonged stimulation of macroautophagy. According to this hypothesis, it is shown that life-long weekly administration of an anti-lipolytic drug decreases glucose and insulin levels, stimulates autophagy and intensifies anti-aging effects of submaximal CR.