The IIS and mTOR pathways indicate nutrient abundance, so downregulating them prolongs lifespan by reducing cell growth and anabolic metabolism. On the other hand, the AMPk and sirtuin pathways imply nutrient scarcity, so their upregulation prolongs lifespan by reducing nutrient sensing, thus imitating dietary restriction. Some adverse effects caused by upregulating or deregulating these nutrient signaling pathways include compromised wound healing, insulin resistance, cataract formation, and testicular degeneration upon mTOR pathway downregulation by rapamycin administration. Nutritional anti-aging strategy known as calorie restriction has been successfully examined in diverse eukaryotic species. Research efforts have been focused on outlining the molecular mechanisms linking metabolic balance induced by calorie restriction and the biology of aging, thus revealing the key significance of nutrient sensing upon aging. Amino acids regulate multiple, interacting nutrient sensing pathways. The adequate sensing of amino-acid availability is significant for the effective regulation of protein synthesis and catabolism. An important way of amino acid control for nutrient sensing is via the amino acid sensing taste receptors. Taste receptors are members of the T1R and T2R families of G-protein-coupled receptors. Aminoacid taste receptors in humans exhibit a high affinity to glutamate, yet other L-amino acids also operate as ligands, while D-amino acids do not. In a similar way to amino-acid taste sensing by T1R1-T1R3, a T1R2-T1R3 heterodimer constitutes the glucose taste receptor, which is activated by millimolar concentration of glucose, fructose or sucrose. Deregulated nutrient sensing ability takes place upon aging. The significance of nutrient sensing throughout the aging process has been first established in the prominent observation that decreased food intake in rats prolongs lifespan relative to ad libitum fed controls. One of the predominant nutrient sensing dysfunctions that takes place upon human aging is insulin resistance. Upon aging, factors including oxidative stress, inflammation, enzymatic activity disorders and fatty acids accumulation in cells can all contribute to a decline in insulin sensitivity. These changes can be driven by many of the other aging denominators. As a consequence, body gradually loses its capability to regulate blood sugar level, with the pancreas producing more insulin in an effort to compensate. Insulin resistance increases inflammation and oxidative damage, promotes glycation, and alters fat metabolism in liver, thereby advancing atherosclerosis and fatty liver disease. 220