Metabolic Shifts Induced by Caloric Restriction

It is widely accepted that caloric restriction(definition) (CR) without malnutrition delays the onset of aging and extends lifespan in diverse animal models including yeasts, worms, flies and laboratory rodents. The mechanism underlying this phenomenon is still unknown. We have hypothesized that a reprogramming of energy metabolism is the key event in the mechanism of CR and the physiological effects at the cellular, tissue and organismal level may be understood in terms of this initial event. Data will be presented from studies of mice on CR which lend support to this hypothesis. For example, in white adipose tissue, CR increases the expression of genes involved in multiple metabolic pathways. Whether aging retardation occurs in primates on CR is unknown. We are investigating this issue in rhesus monkeys subjected to CR since 1989 and will discuss our hypothesis in the context of data from this cohort. (Supported by NIH P01 AG11915)