Dietary protein and amino acid restriction: Roles in metabolic health and aging-related diseases

The prevalence of obesity is a worldwide phenomenon in all age groups and is associated with aging-related diseases such as type 2 diabetes, as well metabolic and cardiovascular diseases. The use of dietary restriction (DR) while avoiding malnutrition has many profound beneficial effects on aging and metabolic health, and dietary protein or specific amino acid (AA) restrictions, rather than overall calorie intake, are considered to play key roles in the effects of DR on host health. Whereas comprehensive reviews of the underlying mechanisms are limited, protein restriction and methionine (Met) restriction improve metabolic health and aging-related neurodegenerative diseases, and may be associated with FGF21, mTOR and autophagy, improved mitochondrial function and oxidative stress. Circulating branched-chain amino acids (BCAAs) are inversely correlated with metabolic health, and BCAAs and leucine (Leu) restriction promote metabolic homeostasis in rodents. Although tryptophan (Trp) restriction extends the lifespan of rodents, the Trp-restricted diet is reported to increase inflammation in aged mice, while severe Trp restriction has side effects such as anorexia. Furthermore, inadequate protein intake in the elderly increases the risk of muscle-centric health. Therefore, the restriction of specific AAs may be an effective and executable dietary manipulation for metabolic and aging-related health in humans, which warrants further investigation to elucidate the underlying mechanisms.