Review Volume 10, Issue 12 pp 4269—4288

Protein synthesis and quality control in aging

Figure 2. Age-related changes and lifespan modulating aspects of protein synthesis. The eukaryotic mRNA translation cycle is shown. During translation initiation, the 43S complex is formed (top). It harbors the initiator Met-tRNAi delivered by eIF2, which is inactivated upon amino acid starvation, UPR or other stress conditions. The 43S complex is loaded onto the capped mRNA 5’ end with the help of eIF4F, composed of the cap-binding protein eIF4E, a scaffold protein eIF4G, and a helicase eIF4A (not shown). The eIF4E-eIF4G interaction is inhibited by 4E-BP repressor proteins, which are activated during amino acid starvation when mTOR kinase is inactive. During elongation (right), cognate (or sometimes near-cognate) aminoacyl-tRNAs are delivered to the translating ribosome by eEF1A, followed by the peptidyl transferase reaction and eEF2-assisted translocation step (not shown). When the ribosome encounters a stop codon, translation termination occurs (bottom). At this step, the synthesized polypeptide is released by termination factor eRF1, delivered by eRF3 (not shown) and assisted by ABCE1. In some cases, however, the stop codon can be recognized by a non-cognate tRNA, leading to a readthrough event. At the final step (left), ribosome and deacylated tRNA should be removed from the mRNA (recycled) with the help of ABCE1, eIF2D and/or MCT-1/DENR proteins. Most of these events are affected by aging (light-green boxes) or linked to lifespan control (yellow boxes). Known positive and negative effects are shown by up and down arrows, respectively, while controversial or potential regulation is indicated by a question mark.