The caloric restriction paradigm

The ability of caloric restriction (CR) to extend lifespan was first reported in 19351. A deceptively simple intervention of reduced calorie intake in the absence of malnutrition, CR impinges directly on the highly complex process that is aging. Investigations into how CR accomplishes these remarkable effects have the potential to determine which processes contribute to disease vulnerability as a function of chronological age, and to identify factors and processes induced by CR that may be harnessed to develop interventions to enhance disease resilience. Studies to date reveal that CR engages a multiplicity of cellular processes, many of which are responsive to a highly interconnected suite of regulatory molecules. One of the emerging themes is the importance of metabolism in aging and delayed aging by CR, raising the possibility that metabolism itself may be a promising target to counter the diseases of aging.