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

Abstract

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.

Figure 1

Some currently experimental variations on traditional daily food restriction as experimentally investigated by early food restriction researchers. All of these have shown some health benefits in short-term human or life-long rodent studies. Protein restriction is self-explanatory, short-term fast refers to 2–3 day water only fasts, alternate day fast is self-explanatory, time-restricted eating describes confining one’s eating to a restricted number of hours (usually 4–6) during the day [45], the fast-mimicking diet is consumption of a ‘fast mimicking,’ that is, low protein, low calorie, diet for 5 consecutive days every month [46], and the 5:2 diet is an intermittent restriction diet in which practitioners severely restrict food intake for two consecutive days each week and eat normally the other five days [42].