Extending healthy life span--from yeast to humans

When the food intake of organisms such as yeast and rodents is reduced (dietary restriction), they live longer than organisms fed a normal diet. A similar effect is seen when the activity of nutrient-sensing pathways is reduced by mutations or chemical inhibitors. In rodents, both dietary restriction and decreased nutrient-sensing pathway activity can lower the incidence of age-related loss of function and disease, including tumors and neurogeneration. Dietary restriction also increase life span and protects against diabetes, cancer and cardiovascular disease in rhesus monkeys, and in humans it causes changes that protect against these age-related pathologies. Tumors and diabetes are also uncommon in humans with mutations in the growth hormone receptor, and natural genetic variants in nutrient-sensing pathways are associated with increased human life span. Dietary restriction and reduced activity of nutrient-sensing pathway may thus slow aging by similar mechanisms, which have been conserved during evolution. We discuss these findings and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible side effects.