Review
When a calorie is not just a calorie: Diet quality and timing as mediators of metabolism and healthy aging

Maria M. Mihaylova 1 2, Amandine Chaix 3, Mirela Delibegovic 4, Jon J. Ramsey 5, Joseph Bass 6, Girish Melkani 7, Rajat Singh 8, Zheng Chen 9, William W. Ja 10, Michele Shirasu-Hiza 11, Mary N. Latimer 12, Julie A. Mattison 13, Anna E. Thalacker-Mercer 14, Vishwa Deep Dixit 15 16 17 18, Satchidananda Panda 19, Dudley W. Lamming 20 21


Summary

An epidemic of obesity has affected large portions of the world, increasing the risk of developing many different age-associated diseases, including cancer, cardiovascular disease, and diabetes. In contrast with the prevailing notion that “a calorie is just a calorie,” there are clear differences, within and between individuals, in the metabolic response to different macronutrient sources. Recent findings challenge this oversimplification; calories from different macronutrient sources or consumed at different times of day have metabolic effects beyond their value as fuel. Here, we summarize discussions conducted at a recent NIH workshop that brought together experts in calorie restriction, macronutrient composition, and time-restricted feeding to discuss how dietary composition and feeding schedule impact whole-body metabolism, longevity, and healthspan. These discussions may provide insights into the long-sought molecular mechanisms engaged by calorie restriction to extend lifespan, lead to novel therapies, and potentially inform the development of a personalized food-as-medicine approach to healthy aging.