Synthesis, modifications, and turnover of proteins during aging

Slowing down of bulk protein synthesis is one of the most commonly observed biochemical changes during aging. The implications and consequences of slower rates of protein synthesis are manifold, including a decrease in the availability of enzymes for the maintenance, repair, and normal metabolic functioning of the cell, an inefficient removal of inactive, abnormal, and damaged macromolecules in the cell, the inefficiency of the intracellular and intercellular signalling pathways, and a decrease in the production and secretion of hormones, antibodies, neurotransmitters, and the components of the extracellular matrix. Age-related changes in the activity, specificity, and stability of a large number of proteins have been reported. However, the molecular mechanisms responsible for such alterations are still poorly understood. Studies on various components of the protein synthetic machinery have revealed a decline in the efficiency and accuracy of ribosomes, an increase in the levels of rRNA and tRNA, and a decrease in the amounts and activities of elongation factors. Because posttranslational modifications of proteins determine their activity and stability, alterations in the extent and level of various modifications such as phosphorylation, methylation, ADP-ribosylation, oxidation, glycation, and conformational changes during aging are being studied. Changes in the regulation of protein synthesis, posttranslational modifications, and protein turnover are crucial determinants of age-related decline in the maintenance, repair, and survival of the organism.