Figure 4.

Proteolytic pathways are the last line of defense against AGE-derived proteotoxicity. Under homeostatic conditions (green box), different proteolytic pathways (UPS and autophagy) act to avoid the accumulation of toxic AGEs. Under high levels of glycative and oxidative stress and/or aging (orange box), the production of AGEs is boosted and tissue fitness is compromised as result of glycation-derived protein aggregation and cytotoxicity. Proteolytic capacities are insufficient to lower AGEs levels because of age-related changes in UPS and autophagy along with the inhibitory effect of glycative stress on proteolytic function.