Dr. Mitchell is an Associate Professor of Genetics and Complex Diseases at the Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, MA. Dr. Mitchell’s research focuses on nutritional, genetic and molecular mechanisms of adaptive stress resistance. His primary interest is in dietary restriction, best known for its ability to extend lifespan in organisms as diverse as roundworms, fruit flies, and yeast, but also with the proven ability to improve metabolic fitness and stress resistance.

Lifespan/healthspan benefits of reduced protein intake without calorie restriction

Dietary restriction (DR) encompasses a range of dietary interventions that are defined functionally by their ability to slow aging and reduce the risk of chronic disease. Experimental DR regimens in rodents can be divided into those involving enforced food restriction vs. those fed on an ad libitum basis. Calorie restriction, intermittent fasting and time-restricted feeding are examples of the former, with lifespan/healthspan benefits in rodents overlapping those of regimens involving reducing dietary protein/carbohydrate ratio or altered amino acid composition (e.g. restriction of sulfur amino acids methionine and cysteine) without enforced calorie restriction. In humans, plant-based diets are associated with reduced risk for chronic diseases including obesity and metabolic syndrome, but the molecular basis remains unknown. Here we tested the hypothesis that the benefits of plant-based diets are due to either differential protein content or amino acid composition of plant vs. animal protein sources. To this end, individual food items were analyzed using the USDA Nutrient Database and in dietary records from NHANES. In all individuals, total protein intake was significantly positively associated with multiple cardiometabolic risk factors including fasting blood glucose, fasting insulin and waist circumference, but this was independent of protein source or amino acid composition. Experimental testing of the effects of protein amount vs. amino acid composition in mice using semi-purified or naturally-sourced diets confirmed the significant main effects of total protein, but not amino acid composition, on healthspan markers. We conclude that modulation of dietary protein intake independent of plant vs animal protein source or amino acid composition is associated with improved chronic disease risk factors in humans and controlled mouse studies, and can at least partially explain the benefits of plant-based diets.