Caloric restriction, gene expression, and aging.

Abstract

Abstract Caloric restriction (CR) increases maximum life span in many species. In laboratory rodents, CR started either early in life or in middle-age opposes the development of age-associated biological and pathological changes. Three main questions are being asked by CR investigators. How does CR retard aging and disease processes? There is evidence that CR lowers oxidative stress generated by mitochondrial oxidative energy (i.e., calorie) metabolism. This lowering is most profound in post-mitotic tissues. Using microarrays, we have described the gene expression profile of aging skeletal muscle, heart and brain in mice and its alteration by CR. We observed that CR opposes the development of many age-associated changes while shifting the level of expression for many genes which are stable in expression with aging in normally fed mice. Does CR retard aging in primates? Two ongoing studies in rhesus monkeys on CR plus epidemiological data support the idea of human translatability. Whether CR extends life span in monkeys should become known in ∼15 years. Studies in humans on CR were launched by the NIA in 2002. Can substances be found which mimic the beneficial actions of CR? The search for “CR mimetics” should benefit from genomic and proteomic approaches.