The anti-ageing effects of caloric restriction may involve stimulation of macroautophagy and lysosomal degradation, and can be intensified pharmacologically

Caloric restriction (CR) and a reduced growth hormone (GH)-insulin-like growth factor (IGF-1) axis are, associated with an extension of lifespan across taxa. Evidence is reviewed showing that CR and reduced insulin of GH-IGF-1 axis may exhibit their effects at least partly by their common stimulatory action on autophagy, the cell repair mechanism responsible for the housekeeping of cell membranes and organelles including the free radical generators peroxisomes and mitochondria. It is shown that the life-long weekly administration of an anti-lipolytic drug may decrease glucose and insulin levels and stimulate autophagy and intensify anti-ageing effects of submaximal CR. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.