Beyond calorie restriction: aging as a biological target for nutrient therapies.

Arguably, the most important discovery in the biology of aging to date was that simply reducing food intake extended life and improved many aspects of health in a diversity of animal species. The conventional wisdom that emerged from first 50 years of rodent food restriction studies included (1) that the longevity impact of restriction was greater the longer restriction was imposed, and (2) that restricting calories rather than any specific macronutrient was critical to its health and longevity benefits. However these assumptions began to crumble as more and more restriction research was performed on other species besides laboratory rodents. Recent investigations of flies, rodents, monkeys, and increasingly humans, has begun to parse how calorie restriction, protein restriction, intermittent fasting, and the temporal pattern of eating all impact the health benefits of food restriction. Fly research continues to inform, as it has repeatedly shown that genotype, age, sex, duration, and tempo restriction all affect the health impact. Ultimately, optimizing human diets will require a personalized approach using omics approaches.