Aging modifies concentration and metabolism of amino acids and associated receptor functionality in the brain

With aging, it is well known that protein synthesis in the body is decreased. This decreased protein synthesis is the case in the brain where there is high regional heterogeneity in amino acid metabolism associated with aging. Metabolites from l-tyrosine as catecholamines; from l-tryptophan as serotonin, melatonin, and kynurenic acid; and from l-arginine as nitric oxide are altered by aging. Not only is the metabolism of amino acids altered, but levels of glutamate receptors such as N-methyl-d-aspartate (NMDA), a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate subreceptors, and nitric oxide synthase are changed. d-Serine, an important amino acid that acts as a coagonist that regulates NMDA receptor activity, is decreased with aging. The mechanistic target of rapamycin, mTOR, integrates diverse environmental and intracellular signals, and senses l-leucine and l-arginine. mTOR inhibition increases lifespan. In addition, the gut microbiota influences functions of the host brain by affecting amino acid metabolism in an age-dependent manner.