The regulation of healthspan and lifespan by dietary amino acids.

As a key macronutrient and source of essential macromolecules, dietary protein plays a significant role in health. For many years, protein-rich diets have been recommended as healthy due to the satiety-inducing and muscle-building effects of protein, as well as the ability of protein calories to displace allegedly unhealthy calories from fats and carbohydrates. However, clinical studies find that consumption of dietary protein is associated with an increased risk of multiple diseases, especially diabetes, while studies in rodents have demonstrated that protein restriction can promote metabolic health and even lifespan. Emerging evidence suggests that the effects of dietary protein on health and longevity are not mediated simply by protein quantity but are instead mediated by protein quality - the specific amino acid composition of the diet. Here, we discuss how dietary protein and specific amino acids including methionine, the branched chain amino acids (leucine, isoleucine, and valine), tryptophan and glycine regulate metabolic health, healthspan, and aging, with attention to the specific molecular mechanisms that may participate in these effects. Finally, we discuss the potential applicability of these findings to promoting healthy aging in humans.
Competing Interests: CONFLICT OF INTEREST STATEMENT D.W.L has received funding from, and is a scientific advisory board member of, Aeovian Pharmaceuticals, which seeks to develop novel, selective mTOR inhibitors for the treatment of various diseases. The University of Wisconsin-Madison has applied for a patent for the use of diets with reduced levels of specific amino acids to promote metabolic health, for which DWL is an inventor.