Evolutionary medicine: from dwarf model systems to healthy centenarians

Abstract

Restriction of the number of calories consumed extends longevity in many organ-isms. In rodents, caloric restriction decreases the levels of plasma glucose and insulin-like growth factor I (IGF-1) and postpones or attenuates cancer, immunose-nescence, and inflammation without irreversible side effects. In organisms ranging from yeast to mice, mutations in glucose or IGF-I–like signaling pathways extend life-span but also cause glycogen or fat accumulation and dwarfism. This information suggests a new category of drugs that could prevent or postpone diseases of aging with few adverse effects. Restriction of caloric intake (CR) extends longevity in organisms from yeast to mice (1, 2) and postpones or prevents a remarkable array of diseases and age-dependent deterio-ration, without causing irreversible develop-mental or reproductive defects. By contrast, most genetic manipulations that extend life