The amazing ubiquitin-proteasome system: structural components and implication in aging.

Proteome quality control (PQC) is critical for the maintenance of cellular functionality and it is assured by the curating activity of the proteostasis network (PN). PN is constituted of several complex protein machines that under conditions of proteome instability aim to, firstly identify, and then, either rescue or degrade nonnative polypeptides. Central to the PN functionality is the ubiquitin-proteasome system (UPS) which is composed from the ubiquitin-conjugating enzymes and the proteasome; the latter is a sophisticated multi-subunit molecular machine that functions in a bimodal way as it degrades both short-lived ubiquitinated normal proteins and nonfunctional polypeptides. UPS is also involved in PQC of the nucleus, the endoplasmic reticulum and the mitochondria and it also interacts with the other main cellular degradation axis, namely the autophagy-lysosome system. UPS functionality is optimum in the young organism but it is gradually compromised during aging resulting in increasing proteotoxic stress; these effects correlate not only with aging but also with most age-related diseases. Herein, we present a synopsis of the UPS components and of their functional alterations during cellular senescence or in vivo aging. We propose that mild UPS activation in the young organism will, likely, promote antiaging effects and/or suppress age-related diseases.