Protein restriction and branched-chain amino acid restriction promote geroprotective shifts in metabolism

The proportion of humans suffering from age-related diseases is increasing around the world, and creative solutions are needed to promote healthy longevity. Recent work has clearly shown that a calorie is not just a calorie-and that low protein diets are associated with reduced mortality in humans and promote metabolic health and extended lifespan in rodents. Many of the benefits of protein restriction on metabolism and aging are the result of decreased consumption of the three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine. Here, we discuss the emerging evidence that BCAAs are critical modulators of healthy metabolism and longevity in rodents and humans, as well as the physiological and molecular mechanisms that may drive the benefits of BCAA restriction. Our results illustrate that protein quality-the specific composition of dietary protein-may be a previously unappreciated driver of metabolic dysfunction and that reducing dietary BCAAs may be a promising new approach to delay and prevent diseases of aging.

Automated summary

The proportion of people suffering from age-related diseases is increasing worldwide. Recent research has shown that low protein diets, particularly those low in branched-chain amino acids (BCAAs), can reduce mortality and promote metabolic health and extended lifespan in both humans and rodents. This article discusses the emerging evidence that BCAAs play a crucial role in healthy metabolism and longevity, and explores the physiological and molecular mechanisms behind the benefits of restricting dietary BCAAs. The findings suggest that the quality of protein, specifically the composition of dietary protein, may be a previously overlooked factor in metabolic dysfunction and reducing dietary BCAAs could be a promising new approach to delaying and preventing age-related diseases.