Dietary restriction and longevity extension as a manifestation of Hormesis

Restricting the food intake of rats and mice to 60% of ad libitum intake has been shown to significantly slow their aging processes and markedly extend length of life. Evidence is presented that indicates the antiaging action of this dietary restriction is a manifestation of hormesis and acts by enabling the animal to cope with stressors, including the low‐intensity, long‐term intrinsic and extrinsic stressors conjectured to cause aging. A hypothesis is offered for the evolutionarily adaptive basis of the antiaging action of dietary restriction: It proposes that this antiaging action is a byproduct of the evolution of mechanisms that enabled animals living in the wild to survive unpredictable and relatively brief periods of food scarcity. Likely proximate mechanisms of antiaging action of dietary restriction are considered. Enhancement of the stress response genes, particularly the heat shock protein genes, appears to be importantly involved. Evidence indicates that moderate hyperadrenocorticism also plays a significant role. These proximate mechanisms may well be major players in other examples of hormesis.