Calorie restriction in primates: will it work and how will we know?

Dietary caloric restriction is the most robust and reproducible means of slowing aging and extending lifespan and healthspan in short-lived mammals and lower organisms. Numerous aspects of this paradigm have been investigated in laboratories around the world since its inception more than 60 years ago. However, two questions about calorie restriction remain unanswered to this day: (1) By what mechanism does it work? and (2) Will it work in humans? This review will focus on the latter with particular emphasis on evaluation criteria, current studies in primate models, available data, and plans for actual human caloric restriction interventions.