Advancing age and other factors influencing the balance between amino acid requirements and toxicity.

As the average human lifespan increases, so does the recognition that advancing age is associated with changes in nutrient intake and requirements as a consequence of biological, social, and pathological factors. Studies show that whereas protein requirements may not differ significantly between younger and older adults, the adaptive mechanisms and responses to nutritional or pathological stressors may differ and alter the balance between requirement and toxicity of specific amino acids (AAs). As an individual gets older, cardiovascular disease and cancer become the leading causes of morbidity and mortality. Advancing age is also associated with changes in appetite, food intake, and physical activity, all of which can influence protein and AA metabolism. The sulfur amino acids (SAAs) methionine and cysteine recently attracted attention because of their pivotal roles in methyl group metabolism and maintenance of the cellular redox state. Methionine, an indispensable AA, is important for methylation reactions and as a precursor for cysteine, which is the rate-limiting AA for glutathione (GSH) synthesis. On one hand, high intake levels or blood concentrations of methionine are associated with adverse consequences such as hyperhomocysteinemia and endothelial dysfunction, which are risk factors for cardiovascular disease. On the other hand, methionine deficiency is reported to lower the threshold of chemical-induced toxicity and play a role in carcinogenesis. Therefore, it is evident that understanding the biological significance of the interrelationship between SAAs, GSH, and methyl group metabolism is key to determining optimal dietary intakes of SAAs in older individuals.